# Phase 2 Randomized, Double-Blind, Placebo-Controlled Clinical Trial of T3D-959 in Mild to Moderate Alzheimer's Disease Subjects

> **NIH NIH R01** · T3D THERAPEUTICS, INC. · 2022 · $5,526,538

## Abstract

T3D-959 is a novel (non-amyloid/non-tau-directed) new chemical entity aimed at improving dysfunctional brain
glucose energy and lipid metabolism in Alzheimer’s disease (AD). T3D-959 is an orally delivered small
molecule dual nuclear receptor agonist that works to restore and maintain metabolic homeostasis, which when
altered in AD, leads to protein misfolding which causes plaque formation, tangle formation and inflammation.
Exploratory human clinical test results (Phase 2a study) of T3D-959 in mild to moderate severity AD patients
have shown multiple efficacy signals indicating a potential to slow, stop or reverse the course of disease. The
next stage in clinical development of this drug is to validate these observed efficacy signals in a larger and
longer Phase 2 clinical trial statistically powered to measure significant differences versus placebo in outcome
measures of cognition, function, and biomarkers of disease. The Phase 2 randomized, placebo-controlled
‘PIONEER’ Study (Prospective therapy to Inhibit and Overcome Alzheimer’s Disease Neurodegeneration via
Brain EnErgetics and Metabolism Restoration) is assessing multiple T3D-959 dose strengths vs. placebo
(15mg, 30mg & 45mg QD and placebo in a 1:1:1:1 ratio) to identify the most safe and effective dose or doses
to use in subsequent Phase 3 testing. The multi-center trial involves 256 mild to moderate AD patients
(MMSE=14-26) dosed orally once-a-day for 24-weeks. Co-primary outcome measures include the ADAS-
cog11 cognition and ADCS-CGIC global function measures. Secondary outcome measures include executive
function as measured by DSCT and change from baseline in plasma Aβ 42/40 ratio. PIONEER began
enrollment in February 2020. Six weeks later, amid a growing Covid-19 pandemic, all screening and
randomization of new subjects was discontinued with 33 already-randomized subjects continuing their dosing
(“Covid Cohort”). In early April, due to the insurmountable barriers to study conduct posed by the COVID-19
pandemic, the trial was halted with cessation of study medication dosing for all randomized subjects. After two
attempted resumptions of the study, each thwarted by pandemic surges, PIONEER successfully re-started on
March 1, 2021, under an amended protocol with trial adaptations in response to the pandemic (DSMB, NIA,
IRB and FDA approved). A new CRO has been contracted and new U.S. clinical trial sites have been added to
replace those lost due to the pandemic. The pandemic-elicited delay of ca. 13 months resulted in significant
unpredicted ‘sunk’ costs . The requested Administrative Supplement (AS) funding will be utilized to ensure that
PIONEER can be completed in its totality and within the original proposed timeline, despite the pandemic-
related delay. Pandemic-related adaptations to the study have been implemented including Covid-19 testing of
all subjects, new inclusion criteria (e.g., CDR-SOB >3.0 and expanding MMSE range from 16-26 to 14-26), all
electronic data management (CRIO...

## Key facts

- **NIH application ID:** 10444130
- **Project number:** 3R01AG061122-03S1
- **Recipient organization:** T3D THERAPEUTICS, INC.
- **Principal Investigator:** John Didsbury
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $5,526,538
- **Award type:** 3
- **Project period:** 2019-05-01 → 2023-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10444130

## Citation

> US National Institutes of Health, RePORTER application 10444130, Phase 2 Randomized, Double-Blind, Placebo-Controlled Clinical Trial of T3D-959 in Mild to Moderate Alzheimer's Disease Subjects (3R01AG061122-03S1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10444130. Licensed CC0.

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