Clinical evaluation of Phenserine tartrate Extended Controlled Release Tablet (ECRT) formulation in early mild Alzheimer’s disease and mild to moderate traumatic brain injury   4

BACKGROUND AND INTRODUCTION

There is a significant unmet need for Alzheimer's disease therapeutics as well as drugs that favorably impact the consequences of brain injury as it can initiate cascades of biological events that may lead to long-term neurodegenerative disorders such as Alzheimer's disease.

One of the goals of the National Institute on Aging (NIA) is to conduct research to better understand the effects and effectiveness of pharmaceuticals on neurodegenerative disorders and, in particular, AD and traumatic brain injury (TBI). This acquisition shall ensure that NIA is able to evaluate the potential of the candidate AD drug (-)-Phenserine tartrate ECRT formulation in relation to pharmacokinetic and pharmacodynamic measures with regard to achieving steady-state drug concentrations of the agent, and measures of drug/target engagement and efficacy when optimally dosed. Plasma samples obtained from the contract shall be evaluated both at NIA and by other organizations to quantify drug concentrations as well as markers of drug action (such assays will be outside this contract) but shall be undertaken on samples obtained from this contract. Results from these assays will be related to tolerability and/or cognitive/imaging measures obtained within this requirement.

Specifically, this acquisition is to evaluate pharmacokinetic and pharmacodynamic measures of (-)- Phenserine tartrate ECRT formulation in subjects with early mild Alzheimer's disease (AD) in a phase 1/2 clinical trial and in mild to moderate traumatic brain injury (TBI) subjects in a phase 1/2 clinical study. Specifically, the acquisition is to provide clinical services for the approved administration of the drug to two well-characterized patient populations, and to obtain blood and other sample/measures from them under rigorously safe conditions for later evaluation of pharmacokinetic and pharmacodynamic measures associated with drug plasma concentrations, blood markers of drug action, tolerability and brain/blood markers of efficacy.

OBJECTIVE

The objective of this acquisition is to first obtain regulatory and Institutional Review Board (IRB) approvals for, and then to undertake a multiple ascending dose (MAD) clinical study to evaluate the safety, tolerability, and time-dependent pharmacokinetics/pharmacodynamics (particularly acetylcholinesterase (AChE) inhibition) of phenserine tartrate ECRT (Task Order 1). This will involve a classical Multiple Ascending Dose (MAD) study over a duration of approx. 30 days. Thereafter, with an understanding of the optimal dose achieved in the MAD study, to then safely and rapidly titrate up to this optimal dose and evaluate this optimal dose of phenserine tartrate ECRT over an extended time in two patient populations: in AD (Task Order 2) and in TBI subjects (Task Order 3). Dosing for TBI subjects will be for up to 30 days and, thereafter, the subjects will be followed alongside a matching group of placebo' subjects that will be provided best non-pharmacological care (i.e., without phenserine tartrate ECRT). Dosing of AD subjects will be for up to 52 weeks (depending on the availability of phenserine tartrate ECRT) alongside a matching group of placebo subjects that can be administered a standard dose of the drug donepezil (instead of Phenserine tartrate ECRT).

ANTICIPATED CONTRACT TYPE AND PERIOD OF PERFORMANCE

An Indefinite-Delivery-Indefinite-Quantity (IDIQ) contract with 30-month ordering period. Task orders may be issued in accordance with availability of the National Institutes of Health appropriations.

OTHER PERTINENT INOFORMATION

The proposed acquisition was previously posted on SAM.Gov under small business sources sought notice 75N95022R00041.

This is not a Solicitation, and the Government is not committed to award a contract pursuant to this announcement.

The solicitation is anticipated to be posted on SAM.Gov on or about April 12, 2023, and proposals will be tentatively due approximately 30 days after the solicitation release date.