Att-SOW-75N95024Q00371.pdf

FAR Part 11—Describing Agency Needs

STATEMENT OF WORK (SOW)

GENERAL INFORMATION

Title of Project:

Testing associations between whole blood hydroxychloroquine (HCQ) levels and blood biomarkers of neurodegeneration Statement of Need and Purpose:

There is currently a pressing need to identify effective treatments for Alzheimer’s disease (AD).

With the repeated failures of multiple pivotal phase-III clinical trials in patients with AD, it is critical to test novel methods of discovering disease-modifying AD treatments. As part of one completed study called the Drug Repurposing for Effective Alzheimer’s Medicines (DREAM) study, and an ongoing study called the Experimental Validation of candidate Alzheimer’s disease treatments identified by multi-omics analyses (PREVENT-AD) study, the NIA IRP is testing the utility of commonly prescribed, FDA-approved drugs that may be repurposed as `candidate AD treatments.’ These studies have identified the immune-modulator drug hydroxychloroquine (HCQ) to be a promising AD therapeutic. The proposed acquisition will build on this work to test whether levels of whole blood HCQ in patients with systemic lupus erythematosus (SLE; lupus) are related to blood biomarkers of neurodegeneration.

Background Information and Objective:

Research in the NIA IRP has identified several FDA approved drugs through the DREAM study that may target metabolic abnormalities associated with AD and be of utility as effective disease-modifying AD treatments. Repurposing of approved drugs is a promising approach that can accelerate the development of novel AD treatments.

Through the Drug Repurposing for Effective Alzheimer’s Medicines (DREAM) study, the NIA IRP identified that the HCQ administered to patients with rheumatoid arthritis (RA) lowers the risk of incident AD. Further experimental validation of these findings has been completed in cell culture-based phenotypic assays as well as in studies of long-term potentiation (LTP) in the APP/PS1 transgenic mouse model. In results from the Experimental Validation of candidate Alzheimer’s disease treatments identified by multi-omics analyses (PREVENT-AD) study, we have shown that HCQ may reduce levels of plasma neurofilament-light (NfL), a peripheral biomarker of neurodegeneration. In patients administered HCQ, whole blood levels of the drug vary widely and it is unclear whether alterations in blood HCQ concentrations are associated with blood biomarkers of neurodegeneration in humans.

This acquisition has the following objective: 1) To test whether changes in whole blood levels of hydroxychloroquine (HCQ) are associated with alterations in plasma concentrations of blood biomarkers of neurodegeneration in a well-characterized cohort of patients with systemic lupus erythematosus SLE.

Anticipated Period of Performance (POP):

September 30, 2024 – September 29, 2025

SCOPE OF WORK

General Requirements:

Independently and not as an agent of the Government, the Contractor shall furnish all the necessary services, qualified personnel, material, equipment, and facilities, not otherwise provided by the Government as needed to perform the Statement of Work below:

Testing associations between whole blood hydroxychloroquine (HCQ) levels and blood biomarkers of neurodegeneration

Perform assays on plasma samples provided by the NIA IRP using the NULISASeq CNS disease panel to measure 120 biomarkers related to neurodegeneration. 150 microliters each of banked plasma will be provided from 163 unique lupus patients from the Johns Hopkins Lupus cohort (PI; Dr. Michelle Petri). A total of 460 plasma samples will be provided.

Specific Requirements:

LEVEL OF EFFORT:

- Senior researcher 100 labor hours

GOVERNMENT RESPONSIBILITIES

Provide 150 microliters each of banked plasma from 163 unique lupus patients from the Johns Hopkins Lupus cohort (PI; Dr. Michelle Petri). A total of 460 plasma samples will be provided.

DELIVERY OR DELIVERABLES

Electronic copy of excel spreadsheet with results of assays on plasma samples provided by the NIA IRP using the NULISASeq CNS Disease panel within 364 calendar days of receipt of the plasma samples. The timely submission of this deliverable is essential to successful completing this requirement.

REPORTING REQUIREMENTS

The contractor is required to provide written progress reports every 3 months for the contract period 09/30/24 through 09/29/25 with annual reports at the end of each year. The progress report shall cover all work completed and shall present the work to be accomplished. This report shall also identify any problems that arose and a statement explaining how the problem was resolved. This report shall also identify any problems that have arisen but have not been completely resolved and provide an explanation.

Reports shall be as follows:

1. WORD/ PDF document and summary XLS tables detailing all the technical aspects of the experimental methodology used and results of assays on plasma samples provided by the NIA IRP using the NULISASeq CNS Disease panel.

OTHER CONSIDERATIONS

Travel: NA Key Personnel: Senior researcher with expertise in multiplex biomarker assays using sequential immunocomplex and release technology

Information System Security Plan: NA

Data Rights:

The National Institute on Aging shall have unlimited rights to and ownership of all deliverables provided under this contract including reports, recommendations, briefings, work plans and all other deliverables. This includes the deliverables provided under the basic contract and any optional task deliverables exercised by the contracting officer. In addition, it includes any additional deliverables required by contract change. The definition of “unlimited rights” is contained in Federal Acquisition Regulation (FAR) 27.401, “Definitions.” FAR clause 52.227-14, “Rights in Data-General, ” is hereby incorporated by reference and made a part of this contract/order.

Section 508—Electronic and Information Technology Standards:

The contractor is not required to develop, procure, maintain, or use Electronic and Information Technology (EIT) in the performance of the SOW.

Publications and Publicity:

It is expected that the successful completion of the project and receipt of the deliverables specified above will allow investigators in the NIA IRP led by Dr. Madhav Thambisetty to include them in peer-reviewed scientific publications describing their original research carried out in the NIA IRP. At the time of drafting these scientific manuscripts, it is anticipated that Dr.

Thambisetty will consult with the contractor(s) and consider their participation as co-authors on publication(s) arising from the project.

Confidentiality of Information:

The Government will not provide to the contractor any information or data of a personal nature about individual(s) or proprietary information or data pertaining to an institution or organization which is confidential.