RFP_75N95024R00086_Amnd_0002_0002.pdf

(x)

75N95024R00086 x x copies of the amendment; (b) By acknowledging receipt of this amendment on each copy of the offer submitted ; or (c) By separate letter or electronic communication which includes a reference to the solicitation and amendment numbers. FAILURE OF YOUR ACKNOWLEDGEMENT TO BE

RECEIVED AT THE PLACE DESIGNATED FOR THE RECEIPT OF OFFERS PRIOR TO THE HOUR AND DATE SPECIFIED MAY RESULT IN REJECTION OF YOUR

OFFER. If by virtue of this amendment you desire to change an offer already submitted , such change may be made by letter or electronic communication, provided each letter or electronic communication makes reference to the solicitation and this amendment, and is received prior to the opening hour and date specified.

x

NINDS

Bethesda, MD 20892-7511 Disorders and Stroke National Institute of Neurological National Institutes of Health

NIDA-EXEC

Bethesda, MD 20892-7511 National Institute on Drug Abuse National Institutes of Health

08/19/20240002

13. THIS ITEM ONLY APPLIES TO MODIFICATION OF CONTRACTS/ORDERS. IT MODIFIES THE CONTRACT/ORDER NO. AS DESCRIBED IN ITEM 14.

12. ACCOUNTING AND APPROPRIATION DATA (If required) is not extended.is extended, Items 8 and 15, and returning

Offers must acknowledge receipt of this amendment prior to the hour and date specified in the solicitation or as amended , by one of the following methods: (a) By completing

The above numbered solicitation is amended as set forth in Item 14. The hour and date specified for receipt of Offers

11. THIS ITEM ONLY APPLIES TO AMENDMENTS OF SOLICITATIONS

FACILITY CODE CODE

10B. DATED (SEE ITEM 13)

10A. MODIFICATION OF CONTRACT/ORDER NO.

9B. DATED (SEE ITEM 11)

9A. AMENDMENT OF SOLICITATION NO.

CODE

8. NAME AND ADDRESS OF CONTRACTOR (No., street, county, State and ZIP Code)

7. ADMINISTERED BY (If other than Item 6)CODE 6. ISSUED BY

PAGE OF PAGES

4. REQUISITION/PURCHASE REQ. NO.3. EFFECTIVE DATE2. AMENDMENT/MODIFICATION NO. 5. PROJECT NO. (If applicable)

1. CONTRACT ID CODE

AMENDMENT OF SOLICITATION/MODIFICATION OF CONTRACT

08/19/2024

CHECK ONE A. THIS CHANGE ORDER IS ISSUED PURSUANT TO: (Specify authority) THE CHANGES SET FORTH IN ITEM 14 ARE MADE IN THE CONTRACT

B. THE ABOVE NUMBERED CONTRACT/ORDER IS MODIFIED TO REFLECT THE ADMINISTRATIVE CHANGES (such as changes in paying office, C. THIS SUPPLEMENTAL AGREEMENT IS ENTERED INTO PURSUANT TO AUTHORITY OF:

D. OTHER (Specify type of modification and authority) appropriation data, etc.) SET FORTH IN ITEM 14, PURSUANT TO THE AUTHORITY OF FAR 43.103(b).

E. IMPORTANT: Contractor is not is required to sign this document and return __________________ copies to the issuing office.

ORDER NO. IN ITEM 10A.

14. DESCRIPTION OF AMENDMENT/MODIFICATION (Organized by UCF section headings, including solicitation/contract subject matter where feasible.)

The purpose of this Amendment is to:

1) Provide responses to vendor-submitted questions;

2) Revise pgs. 10 (Reporting Requirements), 96 (Page and Formatting Limitations), and 125

(Enhancing Reproducibility through Rigor and Transparency) of the RFP;

3) Incorporate FAR Clause 52.204-23 "Prohibition on Contracting for Hardware, Software, and

Services Developed or Provided by Kaspersky Lab Covered Entities (DEC 2023)" by reference into Section I of the RFP;

Continued ...

16A. NAME AND TITLE OF CONTRACTING OFFICER (Type or print)15A. NAME AND TITLE OF SIGNER (Type or print)

15C. DATE SIGNED 16B. UNITED STATES OF AMERICA 15B. CONTRACTOR/OFFEROR 16C. DATE SIGNED

(Signature of person authorized to sign) (Signature of Contracting Officer)

RIEKA N. PLUGGE

STANDARD FORM 30 (REV. 11/2016)

Prescribed by GSA FAR (48 CFR) 53.243

Previous edition unusable

Except as provided herein, all terms and conditions of the document referenced in Item 9 A or 10A, as heretofore changed, remains unchanged and in full force and effect .

x

ITEM NO. SUPPLIES/SERVICES QUANTITY UNIT UNIT PRICE AMOUNT

NAME OF OFFEROR OR CONTRACTOR

2 2

CONTINUATION SHEET

REFERENCE NO. OF DOCUMENT BEING CONTINUED PAGE OF

(A) (B) (C) (D) (E) (F)

75N95024R00086/0002

4) Revise Attachment 9 - Sample Task Order #2

Statement of Work, Pages 6-7 ("Plasma for PK,"

"IP Administration in CRU," and "Issue Drug for

Home Use");

5) Revise Attachment 10 - Sample Task Order #3

Statement of Work, Pages 6-11, (Plasma for PK);

and

6) Extend the proposal submission deadline to

October 11, 2024, at 5 pm ET.

All other terms and conditions remain unchanged.

Attachment 1: Questions and Answers

Attachment 2: Attachment 9 - Sample Task Order #2

Statement of Work (revised)

Attachment 3: Attachment 10 - Sample Task Order

#3 Statement of Work (revised)

Period of Performance: 04/01/2025 to 03/31/2035

NSN 7540-01-152-8067 OPTIONAL FORM 336 (4-86)

Sponsored by GSA

FAR (48 CFR) 53.110

Phase I Clinical Trials for Development of Small Molecule and Biologics Therapeutics Solicitation number 75N95024R00086

Questions and Answers

General comments on contract structure:

The Government anticipates awarding multiple indefinite delivery/indefinite quantity (IDIQ) contracts from this RFP. Offerors who are awarded an IDIQ contract will be eligible to compete for future Task Order Request for Proposals (TORFPs) when NINDS has a need for Phase I SAD or SAD/MAD trials. Each TORFP will contain trial-specific details, including a draft synopsis and preclinical data. At that time, it will know what the drug product is and what clinical testing is needed on what timeline.

NINDS anticipates issuing TORFPs for a wide range of modalities and indications with varying requirements and thus has a need for contractors who are capable of running a variety of phase I trials so that the Government has adequate support regardless of these variables.

Please note that Sample Task Order SOWs 2 and 3 are merely examples of clinical study requirements that could potentially be solicited through a future TORFP. BPN-XXX is not a sanitation of a propriety compound; it’s a hypothetical compound. The same is true of Protein X. These SOWs do not reflect actual clinical trial needs and, as a result, the Government will not be awarding Task Orders based on offerors’ responses. The purpose of these samples is to give offerors the opportunity to showcase their ability to respond to TORFPs that are similar to what would be issued under an active IDIQ contract and to better enable the Government to evaluate offerors’ technical capabilities and the competitiveness of their pricing. Trial-specific details are missing, because these are not real SOWs and we want offerors to consider the best approach for responding to these scenarios based on the information that’s been provided. We also wanted to avoid giving the impression that all future TORFPs would contain a particular set of requirements given the amount of variability from one clinical trial to another.

In discussing their proposed technical approach for the sample TORFPs, Offerors are expected to describe their relevant organizational capabilities and to demonstrate their knowledge of clinical trial processes and requirements. Offerors are encouraged to outline assumptions they made in their response and to offer alternative options based on their experience with similar work, explaining the benefits and drawbacks of a particular approach. Offerors should also state if assumptions needed to be made that have a large impact on their proposed cost estimate/price. This is why, for example, we’re requesting that the CSF and imaging work to be priced separately.

Question Number

Solicitation Reference

Solicitation Reference Text

Question to Government Government Response

1. SOL_75N95024

R00086, Instructions to Offerors, 1.e., “The substudy proposal section of the Technical Plan (included within the 30 page limit) shall not exceed 8 single-sided or 4 double-sided pages.”

Does NINDS consider each of the two sample task orders studies separate substudies, and therefore, a total limit of 16 pages of the 30 page Technical Plan?

After consideration, the Government has decided to remove all page limitations from the RFP and to allow offerors to determine the necessary size for their proposals. However, Offerors are encouraged to limit the overall size of their technical and business proposals, inclusive of appendices, attachments, etc.

2. SOL_75N95024

R00086, Instructions to Offerors, 1.e., “This page limitation does not include the cover sheet, abstract, table of contents, personnel, facilities, equipment and resources, other considerations, schedule, other support, cost

Is the Offeror’s introduction to the Technical proposal included in the page limitation?

Introductory statements are excluded from the technical proposal page limitation.

information, and literature cited.”

3. SOL_75N95024

R00086, Section M, Technical Evaluation Factors, Page

“Sample Task Order No.

2, - SAD Study (must include a separate technical response); and

(4) Sample Task Order No. 3 SAD/MAD Study (must include a separate technical response).”

Will NINDS please clarify if the separate technical response for Sample Task Orders 2 and 3 include Personnel Qualifications (including resumes) and Organizational Capabilities and Resources?

Please provide information relating to personnel qualifications and organizational capabilities and resources in a separately marked section of the technical proposal.

4. Attachments A9 and A10, Sample TORFP 2 and 3

Outcome Measures: PK To price Sample Task Orders 2 and 3, should Offerors assume any stability or special handling needs for PK and PD analysis?

For costing/pricing purposes, assume there are no special stability or handling instructions for sample task orders 2 or 3. But please discuss your organization’s related capabilities with its’ technical proposal as it is possible that future task orders will require special capabilities.

5. Attachments A9 and A10, Sample TORFP 2 and 3

Outcome Measures: PK To price Sample Task Orders 2 and 3, should Offerors assume critical reagents and reference materials will be available?

Yes.

6. Attachment A10, Sample TORFP 3, Page

Objectives Which of the following assay formats should Offerors assume for Sample Task Order 3 PK sample analysis?

• LCMS

• ELISA

• MSD

As this is a sample task order SOW, the requested details are not currently available. But please clearly state any assumptions that were made for costing/pricing purposes. Additionally, please discuss your organization’s related capabilities in its’ technical proposal. Future TORFPs could require different assays, which will be fully described in the corresponding SOW.

7. Attachment A10, Sample TORFP 3, Page

Objectives Which of the following assay formats should Offerors assume for Sample Task Order 3 PD sample analysis?

• LCMS

• ELISA

• MSD

Please see the above response.

8. Attachment

A9, Sample TORFP 2, Pages 6-7

Plasma for PK Will NINDS confirm the PK sample collection on Day -1 is an error and may be removed?

Yes, this document has been revised to correct the error.

9. Attachment

TORFP 3, Pages 6-11

Plasma for PK Will NINDS confirm the PK sample collection on Day -1 is not needed as pre-dose samples on Day 1 are collected?

10. Attachment A10, Sample TORFP 3, Page

Automated visual fields Is an ophthalmologist required to perform these assessments, or is the site PI able to complete the proper training and administer?

As this is a sample task order SOW, the requested details are not currently available. But please clearly state any assumptions that were made for costing/pricing purposes. Additionally, please discuss your organization’s related capabilities in its’ technical proposal. Future TORFPs could include different requirements, which will be fully described in the

11. Attachment

TORFP 3, Page

Automated visual fields Will NINDS please specify the device required for these assessments?

Please see the above response.

12. Attachment A9, Sample TORFP 2, Page

IP Administration in CRU As this is a SAD study, should Offerors assume the dosing on Days 2 and 3 in Table 3 are errors?

13. Attachment A9, Sample TORFP 2, Page

Issue Drug for Home Use As this is a SAD study, should Offerors assume the Issue Drug for Home use on Day 3 is an error?

14. Attachment A9, Sample TORFP 2, Page

MRI Imaging of head and CT of head

Will the MRIs and CTs be used for exclusion criteria or as study endpoints?

As this is a sample task order SOW, the requested details are not currently available. But please clearly state any assumptions that were made for costing/pricing purposes. Additionally, please discuss your organization’s related capabilities in its’ technical proposal. Future TORFPs could have different requirements,

15. Attachment

TORFP 2, Page

CSR PK collection, MRI Imaging of head, and CT of head

Should Offerors provide a cost per collection or will NINDS provide number of subjects and timepoints for full study costing?

As this is a sample task order SOW, the requested details are not currently available. But please clearly state any assumptions that were made for costing/pricing purposes. NINDS will provide the number of subjects for any clinical study TORFPs issued after award of the parent contracts.

16. Attachment

TORFP 2, Page

CSF PK collection and analysis

If NINDS requires study costing for CSF collections, should Offeror assume 2 punctures per subject?

As this is a sample task order SOW, the requested details are not currently available. For pricing purposes, please assume 1 puncture per participant.

Additionally, please discuss your organization’s related capabilities in its’ technical proposal. Future clinical study TORFPs could have different requirements, which would be fully described in the corresponding task order SOWs.

17. Attachment

TORFP 2, Page

“Consistent with NINDS policies, efforts should be made to enroll males and females and include diverse races and ethnicity.”

For subject recruitment purposes, are there any set standards the clinic must follow during recruitment of the participant population, such as exactly a 50/50 split of Male to Female or attempting to exactly match the study population to the racial makeup of the clinic’s location?

Vendors are expected to make every effort to support the goals of the NIH inclusion policies and should discuss their related capabilities within their technical proposals. However, it is not expected that exact numbers would be required for sex, gender, race, ethnicity or age distribution unless there’s an unusual/special circumstance.

18. Attachment

A7, IDIQ

Contract Statement of Work, Section Base: vi.b. Page

“Ensure all requisite regulatory approvals are in place (e.g., IRB and FDA submissions) including that the investigational agent has appropriate FDA clearance (i.e., IND) confirming the agent’s

Please confirm if NINDS require regulatory support in preparing the initial IND submission?

No, the trial Sponsor would be responsible for this.

suitability for testing in humans prior to initiating recruitment in compliance with all NIH policies, FDA regulations and International Conference on Harmonization (ICH) Good Clinical Practices (GCP) guidelines.”

19. Attachment

Contract Statement of Work, Section Base: vi.f. Page

“additionally, the IND report for annual filing requirements to the IND application, as needed”

What level of support is required for IND report for annual filing?

The trial Sponsor will be responsible for reporting to the FDA, but please assume they will need support with gathering the necessary information and preparing the documentation. Also please note that individual clinical trial requirements may vary.

20. Attachment

Contract Statement of Work, Section Base: vi.f. Page

“Prepare a complete clinical study report in submission ready format for FDA unless otherwise specified.”

Please confirm pricing of the clinical study report will be included in the Option as noted on Page 12 and not the Base as mentioned on Page 8.

Yes, this is part of the option.

21. Attachment

A7, IDIQ

Contract Statement of Work, Section Base: iii, Page 5 and Quantity Option: A.ii, Prepare protocol amendments and modifications as required

For pricing of Sample Task Orders 2 and 3, should the Offerors assume one substantial protocol amendment during the Option?

This assumption appears reasonable. Please clearly state any assumptions that were made for costing/pricing purposes.

Additionally, please discuss your organization’s related capabilities in its’ technical proposal.

Questions and Answers

22. Attachment A7, IDIQ Contract Statement of Work, Section D.iv., Page 13

Provide Clinical Imaging Facility

Is a central repository needed to collection and store images?

Please discuss your organization’s related capabilities in its’ technical proposal and specify any assumptions that have been made for costing/pricing purposes.

Future clinical study TORFPs could have different requirements, corresponding SOWs.

23. Attachment A7, IDIQ Contract Statement of Work, Section D.vi.c, Page 14

“Clinical data warehousing capabilities/facilities in order to provide a centralized, integrated system for data storage, analysis, reporting and ad hoc query of clinical data”

Will NINDS please confirm if a single data warehouse for all projects is required or if each awardee will have its own data warehouse?

Please see above response.

24. Attachment A7, IDIQ Contract Statement of Work, Section D.vi.e, Page 14

“Provide other facilities and equipment, as may be specified by the task order protocols (e.g., biosafety laboratory facilities in compliance with Federal and state regulations)”

Will NINDS please confirm if a biosafety laboratory facility is required for this contract and clarify its connection to the Data Management Center?

Please see above response.

25. Attachment A22, PHS Human Subjects and Clinical Trials Information

Will NINDS please confirm if this attachment must be completed for Sample Task Orders 2 and 3?

If this form is to be completed and included in the appendices, will it be included in the maximum 50 page limit?

This attachment was included as a reference document and will only need to be completed as part of responses to clinical study TORFPs that are issued after award of the parent contract vehicle.

26. Attachment A23, Protection of Human Subjects

Will NINDS please confirm if this attachment must be completed for Sample Task Orders 2 and 3?

If this form is to be completed and included in the appendices, will it be included in the maximum 50 page limit?

Please see above response.

27. When task orders are released and the scope of work is known, may additional subcontractors be added as appropriate, or must they be preapproved within the response to this solicitation at the IDIQ level?

It is not necessary for every subcontractor that an offeror could potentially utilize in performance of this requirement to be pre-approved prior to award of the IDIQ contract vehicle. If an offeror is awarded an IDIQ contract, they may propose additional subcontractors, if appropriate, in their responses to individual clinical study TORFPs.

However, offerors are required to discuss their organizational capabilities within their technical proposals for this RFP and to clearly state which of the specific requirements (both within the parent contract SOW and the sample task order SOWs) it can perform in-house and which would potentially require the use of a subcontractor.

28. Given that the receipt of the questions by the Government to proposal submission is only four weeks and Offerors will need to modify their proposals and costs based on the answers to the questions, would the Government consider an extension of submission to four weeks after publication of the answers?

After consideration, the Government has decided to extend the proposal submission deadline to October 11, 2024, at 5 pm ET.

We believe this will provide sufficient time for offerors to review the Government’s responses and modify their proposals, if necessary. However, the Government reserves the right to extend the submission deadline at a future date if it determines it to be in its’ best interest.

29. RFP, Page 10, Section C,

1. Reporting Requirements

“In addition, one hardcopy of each report shall be submitted to the Contracting Officer”

Where is the one hard copy to the COR to be delivered?

The reference text was inadvertently included in the RFP and has now been deleted. Any reports/deliverables prepared for this requirement should only be submitted electronically.

30. RFP, Page 18, Section F 2.

Deliveries

Is it anticipated that review of the protocol prior to delivery of final in 3 weeks (15 days) of the TO award by the client and Sponsor will be required? If so, what is the turnaround time to facilitate this timeline?

Yes, it is anticipated that Sponsor review of the protocol will be required. Turnaround time will vary by individual task order.

Please state any related assumptions that have been made for costing/pricing purposes.

31. RFP, Page 18, Section F 2.

Deliveries

What is the expected turnaround time for client/Sponsor review of the Draft CSR?

Turnaround time will vary by individual task order. Please state any related assumptions that have been made for costing/pricing purposes.

32. Enhancing Reproducibility Through Rigor and Transparency on pages 124 and 125 of the solicitation

“Specifically, the offeror shall describe in its technical proposal the information described below”

There is no information below to indicate what to include. Please provide the information to be included in the technical proposal and whether it is to be included in the “Other Considerations” section.

Details on the NIH policy can be found here:

https://grants.nih.gov/policy/repr oducibility/index.htm

This is a general NIH requirement but many of the details of this policy might not be applicable since NIH will be providing details on the design and supporting data to the vendor with each TORFP. As a result, the Government has removed the solicitation reference text; offerors are simply required to address how they will comply with the overall policy.

Offerors are free to determine where to provide this information so long as it’s included within a clearly marked section of their technical proposals.

33. RFP Non-Scored Factors, pg. 152

Should the following items included in “Other Non-scored Factors” be included in the “Other Considerations” section of the technical proposal?

(Authentication of Key Biological and/or Chemical Resources, Electronic and Information Technology Accessibility – Section 508, Obtaining and Disseminating Biomedical Research Resources)

Offerors are free to determine where to provide information related to the non-scored factors so long as it’s included within a clearly marked section of their technical proposals.

https://grants.nih.gov/policy/reproducibility/index.htm https://grants.nih.gov/policy/reproducibility/index.htm

34. RFP Mandatory Evaluation Criteria, pg. 149

Are the Mandatory Qualification Criteria A through D, pages 149 and 150, to be included in the “Other Support Information” section of the technical proposal?

Offerors are free to determine where to provide information related to the mandatory qualification criteria so long as it’s included within a clearly marked section of their technical proposals.

35. Summary of Related Activities and Tech Proposal Cost Summary

Are the Summary of Related Activities and the Technical Proposal Cost Summary to be in the “Other Support Information” section of the technical proposal or in the Attachments?

Offerors are free to determine the placement of the completed Summary of Related Activities and Technical Proposal Cost Summary so long as they are included within a clearly marked section of their technical proposals.

36. A8 - Sample

TORFP #1 SOW

Please define the key personnel role for Senior Research Scientist and qualifications expected.

The labor categories included in the Key Personnel table should be regarded as suggestions. Offerors are free to determine which key personnel they believe are needed to perform the requirements described in the SOW.

37. A9 - Sample

TORFP #2 SOW

How many samples should be included in the pricing per cohort or study?

For costing/pricing purposes, please use the information provided in table 2 (accounting for any errors that have been noted).

38. A10 - Sample

TORFP #3 SOW

Is there a developed assay for protein X that can be transferred or an assay commercially available?

Protein X is a placeholder for an unknown future pharmacodynamic maker. We do not know what will be available.

Typically, data/methods are available from preclinical work.

Please assume this is the case for costing/pricing purposes but please also discuss any related capabilities within your organization’s technical proposal as specific requirements will vary for individual trials.

39. A10 - Sample

Will there be a previously validated method available for transfer the PK assay?

There will be preclinical methods available.

40. A10 - Sample

Tables 3 & 5 indicate plasma sample collection on Days 6, 8 and 12 for the MAD study, but Table 4 and 6 do not indicate time point collection. What time points will be collected on these days?

TORFPs issued after award of the parent contract will include trial-level details but that information is not currently available. Please clearly state any assumptions that have been made for costing/pricing purposes.

41. A10 - Sample

Table 3, day 1 samples show sample collection up to 4 hours, but no collections for 6-hour to 16-hour. Also, there is a study Day 5 indicated in the table;

should this be “15 (MAD Only)”. Is this table accurate?

The column in question should read “14 (MAD Only).” The remaining information is accurate.

42. A9 and A10 - Sample TORFP #2 and 3 SOWs

Will a SMC be appointed to review dose escalation criteria if the data reviewed by the SRC indicate that dose escalation criteria were not met?

At this time, NINDS does not have plans to do that.

43. Can it be assumed that the product sponsor will provide product indemnification which will flow down to the clinical site(s) conducting the trials?

Yes, but the vendor will be responsible for malpractice insurance and indemnification for trial related injuries to volunteers.

44. Should offerors assume that the NINDS will provide reference standards for PK testing?

Yes, this information will be provided for any clinical study TORFPs issued after award of the parent contract vehicle.

45. For sample TO 2 and 3 and all subsequent TO issued on IDIQ, can it be assumed that the product will be available at award with all the required documentation for Phase 1 use and IND established?

Will the Investigator Brochure be provided?

Since the first part of a task order will be protocol development and then IND submission, no, the IND will not be in hand at the start of the TO award. In some cases, the IB will be available at start of award, but not always. The IB and IND will be provided before the trial execution option. Drug product will be available.

46. Is it intended that the client/sponsor will review all development of clinical documents and plans or just final deliverables? If reviewing, what is the assumed turnaround time?

Yes, the trial Sponsor will want to review all documents. Turnaround time will vary. Please state any related assumptions that have been made for costing/pricing purposes.

47. Will a prefinal protocol be submitted to enable finalization in 3 weeks? If not, the timeline is short based on our experience.

If an offeror believes that any of the timelines provided by the Government are unrealistic or unreasonable, they are encouraged to state this within their proposal.

48. Is NINDS interested in long term storage of clinical samples for future testing for the duration of the IDIQ or does NINDS anticipate samples will be discarded during close out of each TO Clinical Trial?

For costing/pricing purpose, please assume that long term storage will not be required.

49. For each awarded clinical trial, who is responsible party for registering and submitting results to clinicaltrials.gov, the Contractor or the Sponsor, assuming the Sponsor is NIDA/NINDS?

NIH will not be the Sponsor. The Sponsor will be a contributor grantee. Included below is a link to the NIH policy regarding who is responsible for reporting clinical trial results:

https://grants.nih.gov/policy/clini cal-trials/reporting/understanding/ni h-policy.htm

From that policy: “If the NIH-funded clinical trial is an applicable clinical trial under the regulation but the awardee or investigator is not the responsible party, the awardee or investigator will coordinate with the responsible party to ensure that all regulatory requirements are met.”

https://grants.nih.gov/policy/clinical-trials/reporting/understanding/nih-policy.htm

50. CSF collection Option – Please provide, if available, additional information for the frequency/collection timepoints?

TORFPs issued after award of the parent contract will include trial-level details but that information is not available at this time. But please discuss your organization’s related capabilities in its’ technical proposal and clearly state any related costing/pricing assumptions that have been made.

51. MRI of Head and CT of Head – Please provide, if available, additional information for the timing and frequency of these scans? Is the MRI/CT with or without contrast? Of note, specific magnetic strength will need to be detailed in the final protocol.

52. Automated visual fields – Please specify type(s) of automated visual field testing needed? Will automated visual field tests be required across all SAD and MAD cohorts? Currently, automated visual field tests are only required for SAD Cohorts 1 – 3.

53. Electroretinography (ERG) – Please confirm if these will be full-field or multifocal ERGs?

54. Please clarify as there appears to be an ERG timepoint point discrepancies noted between the MAD SOA and Detailed Visit Schedule for Days in Research Unit (examples below). Please confirm whether ERGs will occur at Screening, Day -1, Day 1, Day 8, Day 16, and Day 22 or at Screening, Day -1, Day 1, Day 5, Day 16, and Day 17.

55. RFP, page 96 “The substudy proposal section of the Technical Plan (included within the 30 page limit) shall not exceed 8 single-sided or 4 double-sided pages.”

Can NINDS please clarify whether proposals may include 8 single-sided pages for each sample TORFP (within the 30 page limit) substudy response, or only 8 pages in total for all 3 sample TORFP responses?

Please see the Government’s response to Question #1.

56. A9 - Sample

Is there a Table 1 of the SoA? The schedule starts with Table 2. Are we missing Table 1 or is it a typo?

If by “SoA” you are referring to the Sample TO, table 1 is the synopsis.

57. A9 - Sample

TORFP #2 SOW

The last page of the synopsis (Table 3), under the heading “Day 4”, lists (Cohorts 4-6 only), however, in the rest of the synopsis, Cohorts 4-6 are not singled out for Day 4 assessments.

Can NINDS clarify if all participants receive the same assessments on Day 4, not just Cohorts 4-6?

For costing/pricing purposes, yes, please assume all participants will receive the same assessments on day 4. However, please note that actual clinical study details will only be provided for TORFPs issued after award of the parent contract vehicle.

58. A9 - Sample

Table 3 mentions unique activities for Cohorts 4-6, but the rest of the synopsis suggests that all cohorts are treated the same. Page 2 of the synopsis (under “study Design and Duration”) state “All cohorts will reside in the research unit from Day -1 through Day 3. On Day -1 baseline safety data will be obtained.

Subjects will receive a single oral dose on the morning of Day 1.

Safety and PK will be obtained through Day 3, and then subjects will be discharged from the unit. Subjects return for an outpatient visit on Day 4.” Table 3 suggests that cohorts

Can NINDS clarify what day will participants stop residing in the research unit for each Cohort?

For costing/pricing purposes, please assume all 6 cohorts will be treated the same. However, please note that actual clinical study details will only be provided for TORFPs issued after award of the parent contract vehicle.

4-6 will remain “in the research unit” through Day 4.

59. A9 - Sample

Can NINDS provide what the preclinical tox study (GLP) species plasma BioA method extraction technique is i.e. Protein Crash, Liquid/Liquid, SPE/SLE?

TORFPs issued after award of the parent contract will include trial-level details but that information is not available at this time. As specific requirements will vary for individual trials, please discuss any related capabilities within your organization’s technical proposal.

60. A9 - Sample

Can NINDS provide what the preclinical tox study (GLP) species plasma BioA method extraction technique is i.e. Protein Crash, Liquid/Liquid, SPE/SLE?

61. A9 - Sample

TORFP #2 SOW

There is limited information on the expected CNS penetration for the BPN-xxx asset. Can we assume there is a need to confirm CNS penetration in the SAD/MAD HV studies through CSF sampling or imaging methods?

No, this is not always going to be required. But it could be and, if so, this information would be specified in the actual clinical study TORFP. As specific requirements will vary for individual trials, please discuss any related capabilities within your organization’s technical proposal.

Additionally, NINDS requests that offerors separately price out CSF and imaging since they can have a large impact on cost.

62. A10 - Sample

Offerors should “provide cost estimates for each of these additional studies performed as part of this protocol 1) CSF PK Collection and Analysis;

2) MRI Imaging and Head; and 3) CT of Heat”

It’s not clear in the Synopsis or Schedule of Assessments when these collections should occur.

Can NINDS confirm when each of these collections should occur for each cohort?

For costing/pricing purposes, please assume 1 puncture/scan per participant. However, as specific requirements will vary for individual trials, please discuss any related capabilities within your organization’s technical proposal.

Additionally, NINDS requests that offerors separately price out CSF and imaging since they can have a large impact on cost.

63. A10 - Sample

Can NINDS provide clarification on which Protein X bidder’s should assume for costing purposes?

TORFPs issued after award of the parent contract will include trial-level details but that information is not currently available. As specific requirements will vary for individual trials, please discuss any related capabilities within your organization’s technical proposal and clearly state any related assumptions that have been made for costing/pricing purposes.

64. A10 - Sample

In the SoA for Cohorts 1 – 3 Table 3, Study Day 1, the single dose plasma PK sample times appear to be abbreviated and do not match to ECG or Protein X. Can NINDS clarify if this sampling time is correct?

65. A10 - Sample

TORFP #3 SOW

The scope of work indicates that “Significant safety issues were identified at doses 10-fold above the No-Observed-Adverse-Effect Level (NOAEL) in each of these studies”. Can NINDS please clarify if additional allometric scaling (different species) to determine NOAEL (or MABEL) and FIH starting dose will be needed for confirmation of the dose?

66. Page 5 of 7 within Attachment 9 (Sample Task Order #2 – Statement of Work)

Offerors should “provide cost estimates for each of these additional studies performed as part of this protocol,” including

(1) CSF PK collection and analysis; (2) MRI Imaging of Head; and

(3) CT of Head

Can the timing of these assessments and the expected endpoints to be derived from them be provided?

Also, should offerors also provide similar cost estimates for (1) CSF PK collection and analysis; (2) MRI Imaging of Head; and (3) CT of Head for Sample Task Order #3 provided in Attachment 10?

response to Question #16.

67. Page 96 of the

RFP

The substudy proposal section of the Technical Plan (including within

Does this mean that the three (3) TORFPs have 8 pages each or 8 pages in total?

response to Question #1.

the 30 page limit) shall not exceed 8 single-sided or 4 double-sided pages.

68. Please confirm if there is a page limit for each CV/resume provided for Key Personnel and Other Scientific and Technical Personnel.

There are no page limits for CVs/resumes; however, Offerors are encouraged to limit the overall size of the technical proposal, inclusive of appendices, attachments, etc.

69. A8 – Sample

What does NINDS envision as the day to day responsibilities of the Senior Research Scientist?

response to Question #36.

70. Our interpretation of the statement of work and sample task orders is that the task order awardees will prepare study data for inclusion in the U.S. FDA IND Annual Reports. However, the awardee will not prepare or submit the IND original submission or any IND amendments.

Further, it is our understanding that regulatory affairs review support is only required to ensure suitability of clinical study documentation, including the transfer of regulatory obligations, and address ad hoc regulatory questions concerning study conduct. Would you kindly confirm this interpretation or clarify further?

Yes, that is correct.

71. Pg 19 of Attachment 7 – IDIQ Contract

SOW

Final Statistical Analysis Report

Are the components of this report expected to be different from the statistical methods and results that would be included in the final clinical study report?

Most likely not; however, this could vary for individual trials.

72. Does NINDS have a preference on the approaches to clinical monitoring (e.g., 100% SDV or risk-based)?

Please propose what you recommend based on your organization’s experience and expertise.

73. A10 - Sample Task Order #3 SOW, pg. 2, “Study Design and Duration”

The multiple ascending dose cohorts will start enrollment after completion of the last dose cohort in the single ascending dose portion

Does this mean that 1) the MAD dose cohorts will not begin enrollment until ALL SAD cohorts are completed, or 2) that MAD dose cohort 1 would begin following the completion of SAD dose cohort 1?

For costing/pricing purposes, please assume option 2.

TORFPs issued after award of the parent contract will include trial-level details but that information is not currently available. As specific requirements will vary for individual trials, please discuss any related capabilities within your organization’s technical proposal.

74. Attachment 11 “Additional Technical Proposal Instructions

References a number of sample documents (i.e., sample ICF, sample CRFs).

Please confirm whether these sample documents are expected with the proposal or if the government is looking for a description of the process to develop these documents. If actual sample documents are required, please confirm these are excluded from the page limit.

Sample documents are not required. A description of the process to develop these documents is sufficient.

75. Does NINDS have a specific central biorepository where all specimens need to be sent eventually?

Not at this time.

76. RFP Mandatory Qualification Criteria, pg. 149, C. Compliance with Good Laboratory (GLP) Guidelines

If we propose a bioanalytical lab with OECD-GLP certification, does that meet mandatory qualification criteria C?

We unfortunately cannot provide any technical assessments prior to receipt of proposals. Please propose what you believe is appropriate based on your organization’s experience and expertise.

77. Pg 90, 95, and 137 of the RFP

Pgs. 90 and 95 suggest there may be two contract types but pg. 137 seems to suggest there will only be one contract type. Please clarify.

Offerors are permitted to submit responses for sample task order SOWs 2 and 3 on a firm-fixed-price or cost-reimbursement basis or as a hybrid of the two contract types.

However, as it is not anticipated that all of the work described in the contract SOW can be performed on a firm-fixed-price basis, offerors are required to certify that they possess an adequate accounting system.

78. A7 - IDIQ

Contract SOW

I came across a directory of contractors and CROs associated with the URGENT network. Could you clarify whether one of these entities is expected to serve as the primary contractor, with Phase I studies potentially being subcontracted?

These contracts were awarded specifically for biologics manufacturing and nonclinical services and biologics subject matter expert consulting services.

Any new contract vehicle awarded for Phase I clinical trials would be entirely independent from these contracts and would not necessarily be issued to the same organizations.

79. Could you confirm if prior government contract experience is a prerequisite?

Prior Government experience is not a pre-requisite to responding to the RFP.

80. A7 - IDIQ

“It is anticipated that these task orders will be awarded through a competitive, Task Order Requests for Proposals (TORFP) process, will be cost reimbursement/ completion, fixed price, OR a combination of both, and will have variable periods of performance.”

Do you anticipate that an IDIQ contract will be awarded for overall Project Management, Protocol Development and Trial Preparation and then multiple TORFP’s will be issued yearly for trial implementation and the incumbent awarded the IDIQ can choose whether or not to submit a proposal for trial execution of each individual clinical project? In other words – is the intent to issue an IDIQ for study start up and to support vendor contracting and the TORFPs to be separate and competitive for the Phase 1 centers trial execution?

Please note that funding will only be obligated at the task order level. The Government anticipates issuing multiple IDIQ contracts as a result of this RFP. Concurrent with contract award, the Government intends to issue a task order to each contract awardee for a kickoff meeting and project management plan, the SOW for which was included as RFP Attachment #8.

All subsequent task orders will be awarded as the result of competitive TORFPs that are issued to all contract holders, unless there are exceptional circumstances. These task orders will include a base requirement for “protocol development and trial preparation” and a quantity option for “trial implementation,” which may be exercised at the Government’s discretion.

81. A7 - IDIQ

Will FISMA standards apply to the data management in the sample task orders?

No, FISMA standards are not applicable to either the parent contract vehicle or any resulting task orders.

82. A8 - Sample

For the Sample Task Order #1, the essential Senior Research Scientist would be proposed as a subject matter expert from the Duke Department of Neurology or Psychiatry. We are including key scientific experts in our proposal, but the specific scientist will be dependent upon the task order subject area and product-specific dossier. Are biosketches required at this time for all proposed scientific experts?

Offerors are required to include biosketches for all proposed key personnel. However, the only individuals that the Government intends to list as key personnel at award are those proposed for performance of the parent contract and Sample Task Order #1.

83. A9 and A10 - Sample TORFP #2 and 3 SOWs

Will the statistical analysis proposed for the Sample #2 and Sample #3 Task Orders require CDISC standards?

TORFPs issued after award of the parent contract will include trial-level details but that information is not currently available. As specific requirements will vary for individual trials, please discuss any related capabilities within your organization’s technical proposal.

Additionally, please clearly state any assumptions that have been made for costing/pricing purposes.

84. A9 and A10 - Sample TORFP #2 and 3 SOWs

Will interim PK analysis be performed between cohorts in Sample #2 or Sample #3?

Yes

85. A9 - Sample

For the proposed CT and MRI imaging of the head, will contrast agent be needed? If contrast is needed, should the facility’s SOC agent be utilized?

TORFPs issued after award of the parent contract will include trial-level details but that information is not currently available. As specific requirements will vary for individual trials, please discuss any related capabilities within your organization’s technical proposal.

Additionally, please clearly state

86. A9 - Sample

For the proposed CT and MRI imaging of the head, will clinical interpretation be needed?

If imagining is requested, yes, clinical interpretation would be needed.

87. A9 - Sample

For the proposed CT and MRI imaging of the head, will deidentified images need to be submitted to a third party?

Data would need to be shared with the trial Sponsor.

88. A9 and A10 - Sample TORFP #2 and 3 SOWs

Are female subjects enrolled in the Sample Study #2 and #3 required to be either postmenopausal or surgically sterile to enroll, as the concomitant medications states that hormonal contraceptives are permitted?

TORFPs issued after award of the parent contract will include trial-level details but that information is not currently available. As specific requirements will vary for individual trials, please discuss any related capabilities within your organization’s technical proposal.

Additionally, please clearly state

89. A9 - Sample

Sample #2 is a SAD design study, but shows IP administration on Days 1, 2, and 3, along with issuing drug for home use on D3?

response to Question #12 and 13.

90. A10 - Sample

Within Table 3 of Sample #3, many of the PK timepoints occur at the same time as the ERG. Is there a priority for performance at that time?

TORFPs issued after award of the parent contract will include trial-level details but that information is not currently available. As specific requirements will vary for individual trials, please discuss any related capabilities within your organization’s technical proposal.

Additionally, please clearly state

91. A9 - Sample

In Table 2 of Sample #2, there is a PK collection at Day -1, in addition to a pre-dose collection on Day 1.

Is this correct?

response to Question #8.

92. A10 - Sample

TORFP #3 SOW

In Table 3 and 6 of sample #3, there is a PK collection at Day-1, in addition to pre-dose collection on Day 1. Is this correct?

response to Question #9.

93. A9 and A10 – Sample TORFP #2 and 3 SOWs

Is there information on the stability and storage for the investigational products for A9 and A10 once packaged into

TORFPs issued after award of the parent contract will include trial-level details but that information is not currently available. As specific

Questions and Answers capsules? This determines the frequency of preparation for the capsules as we would plan to batch the doses for a cohort together at a minimum.

requirements will vary for individual trials, please discuss any related capabilities within your organization’s technical proposal.

Additionally, please clearly state any assumptions that have been made for costing/pricing purposes.

94. A10 - Sample

TORFP #3 SOW

In Sample #3, which specific type of ERG is anticipated (full field, pattern or multifocal)?

Please see above response.

95. A9 and A10 – Sample TORFP #2 and 3 SOWs

In the Exclusion Criteria of Sample #1 and #2, a lower limit for systolic and diastolic blood pressure is specified. Should the Grade 2 CTCAEv5 be utilized as the upper limit for inclusion? I.e.

systolic blood pressure between 90-140 mmHg (inclusive) and diastolic blood pressure between 50-90 mmHg (inclusive).

Please see above response.

96. A9 and A10 – Sample TORFP #2 and 3 SOWs

Both Sample #2 and Sample #3 have stipulated consumption of tobacco should be avoided, however, no testing is required to confirm absence of nicotine derivatives. Should we include the addition of a urine cotinine test to confirm compliance at screening and Day –1?

Please note that trial-level details will only be provided with TORFPs issued after award of the parent contract vehicle. However, Offerors are encouraged to include any testing in their sample TO responses that they would recommend based on the information that’s been provided.

97. A22 - PHS Human Subjects and Clinical Trials Information Form

Should a separate Human Subjects Form be completed for each Sample Task Order and attached to the Technical Proposal, or a single Human Subjects form submitted in eCPS?

Please see the Government’s response to Question #25.

98. A23 - Protection of Human Subjects Assurance Identification

Does an IRB representative need to complete the Protection of Human Subjects Assurance Identification form for this proposal and for future task orders?

response to Question #26.

Sample Task Order #2 - Statement of Work

NOTE: The following sample Task Orders indicated in this attachment are provided to assess the offeror’s capabilities to conduct and fulfill the requirements of the Statement of Work for clinical trials of similar scope and size to be issued under Task Orders awarded in response to this solicitation. These sample Task Orders will NOT be executed nor will awards be issued for the sample work. Offerors are to include in their proposals a response that specifies the methods by which each sample Task Order will be fulfilled with associated costs.

Single Ascending Dose (SAD) Study

1. Scope

The scope of activities includes all tasks and activities associated with the execution of the requested Phase I trial described herein. The development and finalization for the clinical protocol entitled: A Phase I randomized double-blind placebo-controlled study to assess the safety, tolerability, and pharmacokinetics of BPN-XXXXX following single ascending dose administration to healthy volunteers including but not limited to the development and finalization of study design elements, safety assessments, PK assessments and other protocol requirements performed by the Contractor.

Note: The offerors are to provide a technical proposal including timelines and cost estimate for the execution of above referenced protocol. For the purposes of proposal preparations, assume that the Contractor is tasked with designing a Phase I single ascending dose clinical trial to evaluate the safety profile and PK of BPN-XXXXX, a novel neurotherapeutic in healthy adult volunteers. Objectives of the protocol are a) characterize the systemic safety profile of BPN-XXXXX in a single ascending dose trial and b) characterize the PK of BPN-XXXXX across the range of doses.