RFP 75N95022R00041_Amendment 01.pdf

(x)

75N95022R00041 x x

NIA

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

NIDA-EXEC

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

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.

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 Items 8 and 15, and returning ______1_____ 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.

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

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)

04/12/2023

9A. AMENDMENT OF SOLICITATION NO.

CODE

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

To All Potential Offerors

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

PAGE OF PAGES

4. REQUISITION/PURCHASE REQ. NO.3. EFFECTIVE DATE

05/08/2023

2. AMENDMENT/MODIFICATION NO.

5. PROJECT NO. (If applicable)

1. CONTRACT ID CODE

AMENDMENT OF SOLICITATION/MODIFICATION OF CONTRACT

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.

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

Fred Ettehadieh, Contracting Officer

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

15C. DATE SIGNED 16B. UNITED STATES OF AMERICA

/S/

15B. CONTRACTOR/OFFEROR 16C. DATE SIGNED

05/08/2023 (Signature of person authorized to sign) (Signature of Contracting Officer)

STANDARD FORM 30 (REV. 11/2016)

Prescribed by GSA FAR (48 CFR) 53.243

Previous edition unusable

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

PURPOSE: Responses to Questions relevant to responding to this solicitation have been included in the continuation pages. Attachment 23-Additional Business Proposal Instructions-Updated

NOTE: New Offer submission deadline: 4:00 PM local time on 5/24/2023

**SEE CONTINUATION PAGES**

ALL OTHER TERMS AND CONDITIONS OF THE SOLICITATION REMAIN UNCHANGED

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 .

RFP Number: 75N95022R00041 Page 2 of 6 Amendment No. 01

NOTE: New Offer submission deadline: 4:00 PM local time on 5/24/2023

Question 1. Confirm if the $2,000,000 maximum applies to the entire IDIQ (TOs 1, 2, and 3) or whether that simply applies to TO 1.

Response 1. Confirmed. The Government anticipates an IDIQ maximum of $2,000,000. However, this is a negotiated acquisition and offerors may propose a different maximum for the entire IDIQ (to include TOs 1, 2, and 3).

Question 2. Confirm if there is a page limit for the Technical Proposal.

Response 2. Technical proposal has no page limit.

Question 3. For budgeting consistency confirm if DSMBs should be included in each TO.

Response 3. Data Safety and Monitoring Board (DSMB) is not included in these TOs. DSMB is not necessarily essential in single-center open-label Phase I and II clinical trials as the local investigator will have access to all data. In these types of trials, the investigator could appoint an independent medical monitor to evaluate adverse events and make recommendations for continuing or stopping a clinical trial.

Question 4. Confirm if offerors should provide a Technical Proposal response that addresses the IDIQ, TO 1, TO 2, and TO 3, or whether our initial Technical Proposal should solely address the IDIQ and TO 1 at this time.

Response 4. Offerors should provide a technical proposal that includes their approach to completing all activities described in the IDIQ SOW, broken down by each Task Order (Clearly marked sections).

Question 5. Confirm if offerors should assume full-service CRO support for TOs 1, 2, and 3. Full-service CRO support includes: - Regulatory support/IRB approval - Protocol design and development - Project management - Clinical site feasibility and activation - Clinical conduct and patient recruitment - Clinical site monitoring and site management - Biostatistics/Statistical Programming - Data Management - Medical Writing - Safety/Pharmacovigilance - PK/PD Statistics - Quality Assurance and Compliance - Clinical Supplies - Central and Bioanalytical Lab Support.

Response 5: Full-service CRO support is not essential; however, key aspects described (such as Regulatory support/IRB approval. Project management of the contractor clinical site(s) and monitoring, patient recruitment, data management, bioanalytical lab support (to run an AChE inhibition assay - as detailed in SOWs), etc.) are required.

Question 6. Attachment 3, TO 1 (Page 6) states that the period of performance for TO 1 is 9 months;

however, the Additional Business Proposal Instructions say to assume TO 1 has a period of performance of 12 months. Confirm which period of performance offerors should assume and provide the period of performance for TO 1.

Response 6. TO 1 relates to the Multiple Ascending Dose study - and can proceed as standalone (in AD or healthy elderly volunteers), or if undertaken with AD subjects, these could then feed into TO 2. The proposed period of performance for TO 1 is 9 months. Refer to updated Attachment 23 - Additional Business Instructions.

RFP Number: 75N95022R00041 Page 3 of 6 Amendment No. 01

Question 7. Attachment 3, TO 2 (Page 6) states that the period of performance for TO 2 is 30 months;

however, the Additional Business Proposal Instructions say to assume TO 2 has a period of performance of 12 months. Confirm which period of performance offerors should assume and provide the period of performance for TO 2.

Response 7. TO 2 period of performance is 30 months. Refer to updated Attachment 23 - Additional Business Instructions.

Question 8. Attachment 3, TO 3 (Page 5) states that the period of performance for TO 3 is 24 months;

however, the Additional Business Proposal Instructions say to assume TO 3 has a period of performance of 6 months. Confirm which period of performance offerors should assume and provide the period of performance for TO 3.

Response 8: TO 3 period of performance is 24 months. Refer to updated Attachment 23 - Additional Business Instructions.

Question 9: Attachment 23 states "as part of their business proposal, offerors are required to provide a detailed budget for costs related to TO 1 (Year 1). In addition, also include a detailed composite budget, by task order/contract year, of all costs for the entire 2.5 year ordering period. Separate proposals for TO 2 and TO 3 will be requested later." Based on the guidance above, confirm the following: With the initial proposal submission, are offerors required to submit separate, standalone cost reimbursement budgets for TO 2 and TO 3? Alternatively, are offerors expected to submit a full standalone cost reimbursement budget for TO 1 and high-level ballpark costs for TO 2 and TO 3?

Response 9. Refer to updated Attachment 23 - Additional Business Instructions.

Question 10. For purposes of timeline and budget development, should the offeror assume the full POP for the entire 2.5 years of the project is anticipated to be 12/21/2023 – 6/21/2026 (2.5 years), i.e. 12 months for MAD, 12 months for AD, and 6 months for TBI? Are these projects to be run concurrently or any overlap or all sequential? We understand that the MAD study may need to be completed and data analyzed, but are AD and TBI run concurrently?

Response 10. The different TOs can proceed concurrently and/or in series. For example, TO 1 is an initial MAD study - and, if undertaken in AD subjects, these could potentially be moved directly in to TO 2 (focused on longer term evaluation of the drug in AD subjects).

Question 11. Attachment 3, TO 3 (Page 5) states that samples (plasma) shall be collected under steady-state conditions by the Contractor, and plasma will be frozen to -80o C for later pharmacokinetic assays that shall be performed elsewhere under a separate contract. Confirm if kits and supplies for sample collection should be included in Contractor costs? How long should Contractors assume samples will be stored prior to shipping to NIA. If shipping and logistics of samples to NIA should be included in Contractor costs, provide assumptions for budget comparability.

Response 11. The resultant contractor shall be responsible for taking blood samples, for separating plasma from some of these samples, and for pipetting such samples into multiple vials (0.5 mL) for storage at -80 C. The resultant contractor shall be responsible for storage of these samples at -80 C and for shipping to NIA. Shipping samples to NIA need not be at the end of the study but can occur on a regular basis (for example, on completion of every 6 or 12 study subjects).

RFP Number: 75N95022R00041 Page 4 of 6 Amendment No. 01

Question 12. Would the Government provide a list of the FAR clauses anticipated to be included by reference in the contract?

Response 12. The solicitation includes all applicable provisions and clauses. Any clauses included in the solicitation are anticipated to be included in the resultant contract.

Question 13. This article states that the contractor should “Report any discovered or unanticipated threats or hazards by either the agency or contractor, or if existing safeguards have ceased to function immediately after discovery, within one (1) hour or less, to the government representative(s).” Confirm if the Government is willing to modify the one (1) hour requirement to a 24-hour requirement.

Response 13. There will be no change to this Article.

Question 14. This article requires the contractor to “afford the Government access to the Contractor's facilities, installations, operations, documentation, information systems, and personnel used in performance of this contract to the extent required to carry out a program of security assessment (to include vulnerability testing).” Confirm if the Government is willing to accept modification of this requirement to allow the Contractor to conduct/provide scans without requiring granting external access for vulnerability assessment/scanning to HHS?

Response 14. There will be no change to this Article.

Question 15. In multiple sections of the Task Orders, it is mentioned "blood draw for exosome and blood-based research and safety studies." We understand that there are a number of blood-based labs that will be tested at labs within NIA. - For purposes of budget development, specify what safety labs will need to be drawn and at what timepoints throughout study participation for participants in each of the 3 TOs.

Response 15. Routine safety monitoring is required to evaluate, for example markers of hepatic and renal function, clinical chemistry, level of erythrocyte AChE inhibition and other measures indicated by the independent medical monitor.

Question 16. The offeror only sees brain imaging mentioned in TOs 2 and 3 "To be undertaken by Contractor: Brain imaging (FDG PET brain imaging x2 or alike brain imaging - to be approved by NIA." - Is the assumption correct that no imaging is required for Task Order 1? Is the expectation to have a central reader for the brain imaging?

Response 16. Confirmed. No brain imaging is required for TO 1.

Question 17. The assessment table noted in TO 2 has several cognitive tests noted and there is mention in TO 3 that the same assessments are to be tested as in TO 2. However, TO 1 does not have any cognitive tests listed. Is the assumption that no cognitive testing is to be done in TO 1 / MAD study?

Response 17. Confirmed. No cognitive assessment is required in TO 1.

Question 18. In one section, TO 3 SOW states, "Dosing for TBI subjects shall be for up to 30 days (i.e., in this TBI focused study (TO 3), (-)-Phenserine dosing will be no more than 30 days). . ."; however, a different section states, "dosing of TBI subjects shall be for 26 weeks – or up to 52 weeks (depending on

RFP Number: 75N95022R00041 Page 5 of 6 Amendment No. 01 the availability of (-)-phenserine tartrate ECRT)." Confirm if dosing is expected to be 30 days, 26 weeks, or 52 weeks.

Response 18. Dosing of (-)-Phenserine tartrate in TO 3 will be for 30 days only. Thereafter, the subjects will then be followed for up to 26 weeks - specifically, they will be followed and time-dependently evaluated at the same times as in TO 2 for AD subjects (in this manner biomarkers evaluated in TO 2 can be compared to biomarkers evaluated in TO 3 - as the samples will have been collected at the same times).

Question 19. For budgeting purposes, advise whether the offeror will be responsible for site payments and participant reimbursement.

Response 19. Confirmed. The resultant contractor shall be responsible for site payments and participant reimbursement.

Question 20. Advise whether NIH will provide drug under study, (-)-Phenserine tartrate Extended Controlled Release Tablet (ECRT) formulation, directly to sites or if offeror should budget for depot services, including packaging, labeling, storage, shipment to sites, and destruction.

Response 20. (-)-Phenserine tartrate will be provided by the NIA, NIH at no cost to the resultant contractor.

Question 21. The Outcomes Measures Table noted in the RFP, TO 2 section, lists several neurocognitive tests (such as MMSE, Cambridge Cognition AD Outcome Battery, ADAS-Cog, and ADCS-ADL). Can you provide further information on the following questions: 1. Will these testing instruments be provided to the offeror in paper or electronic format by NIH? 2. If copyright permission is needed as it may be when these instruments are used in clinical trials, will NIH obtain the copyright permissions, or will the offeror be expected to obtain the copyright permissions? 3. If there is a fee associated with copyright permissions, will NIH pay these fees or expect the offeror to budget for the associated costs? 4. Will these instruments only be provided in English, or will translations be available? If only provided in English, should the offeror include high-level translation costs in the budget?

Response 21. The TOs' SOW indicates a selection of cognitive tests-some will be used as instruments to evaluate cognitive abilities-to be jointly decided by the NIA, NIH and the resultant contractor. The cost associated with use of cognitive instruments shall be the resultant contractor's responsibility.

Question 22. It is noted throughout the RFP document that there are several planned biomarker assays that are to be collected by the contractor and sent to NIH/NIA for actual testing. Confirm if the offeror should include in the budget any costing for a biorepository storage facility to act as an intermediary and receive samples from sites and then ship on to NIH/NIA at appropriate time points when testing is due to commence?

Response 22. Confirmed. The cost for storing biosamples and then shipping them to the NIA, NIH shall be the responsibility of the resultant contractor.

Question 23. Considering low or no SAEs are anticipated, offeror normally assumes the use of a fillable MedWatch/CIOMS as opposed to a safety database. Confirm this is acceptable.

RFP Number: 75N95022R00041 Page 6 of 6 Amendment No. 01

Response 23. Acceptable.

Question 24. There are 3 TOs that, combined, make up the contract. Would offeror need to provide an offer that covers all of the Task Orders (1, 2 and 3) or would we be able to combine Task Order 1 and 2 alone (i.e., without 3) – or some other combination?

Response 24. NIA, NIH is requesting proposals for the entirety of the requirement – this includes all 3 task orders.