T3D-959 for Alzheimer's Disease

Overseen By John Didsbury, Ph.D., Chief Executive Officer

Age: 18+

Sex: Any

Trial Phase: Phase 2 & 3

Sponsor: T3D Therapeutics, Inc.

Must not be taking: Antidepressants, Antipsychotics

Disqualifiers: Psychiatric illness, Stroke, Diabetes, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 78 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new drug, T3D-959, to determine if it can help individuals with mild-to-moderate Alzheimer's disease by improving symptoms and potentially slowing disease progression. Participants will receive either the drug once a day or a placebo (a pill with no active ingredients) for about 78 weeks. The study aims to confirm the drug's safety and effectiveness. Individuals diagnosed with mild-to-moderate Alzheimer's who have a caregiver to assist in reporting their condition might be suitable for this trial. As a combined Phase 2 and Phase 3 trial, this study measures the treatment's effectiveness in an initial group and represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking Alzheimer's research.

Will I have to stop taking my current medications?

The trial requires a washout period (time without taking certain medications) and stability of all concurrent medications according to the exclusion criteria. You may need to stop taking some medications, but the specific details are not provided in the protocol.

Is there any evidence suggesting that T3D-959 is likely to be safe for humans?

Research shows that T3D-959 has been tested in people with mild-to-moderate Alzheimer's disease. Most patients tolerate T3D-959 well. Some studies have examined its safety with regular use, reporting that T3D-959 does not cause major side effects for most people. However, like many new treatments, some individuals might experience minor issues, such as stomach upset or headaches, which are common with many medications. Ongoing research aims to confirm these findings over the long term. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for Alzheimer's?

Most treatments for Alzheimer's disease aim to manage symptoms by targeting neurotransmitters, like donepezil or memantine, which boost brain chemicals involved in memory and judgment. But T3D-959 works differently, targeting nuclear receptors called PPAR delta and PPAR gamma, which are involved in the body's energy and lipid metabolism. This dual-action approach might help tackle the metabolic dysfunctions believed to contribute to Alzheimer's progression. Researchers are excited because this new mechanism could offer a fresh avenue for treating Alzheimer's, potentially improving cognitive functions by addressing these underlying metabolic issues.

What evidence suggests that T3D-959 might be an effective treatment for Alzheimer's?

Research has shown that T3D-959, which participants in this trial may receive, may help treat Alzheimer's disease. In earlier studies, T3D-959 improved certain biological markers, such as the plasma Aβ42/40 ratio and plasma neurogranin, which are linked to Alzheimer's. The drug also showed potential to slow both the symptoms and progression of the disease in patients. Additionally, animal studies have demonstrated that T3D-959 can reduce Alzheimer's symptoms. These findings suggest that T3D-959 might help manage Alzheimer's symptoms and possibly slow the disease's progression. ^{1 2 6 7 8}

Who Is on the Research Team?

John Didsbury, Chief Executive Officer, Ph.D

Principal Investigator

T3D Therapeutics, Inc.

Are You a Good Fit for This Trial?

This trial is for individuals with mild-to-moderate Alzheimer's Disease. Specific eligibility criteria are not provided, but typically participants must meet certain health standards and may be required to have a caregiver or family member who can assist them throughout the study.

Inclusion Criteria

Subject (or legal representative) and caregiver must sign an Informed Consent to participate in the study

Subject has a caregiver who can report on the subject's cognition, function, behavior, safety, compliance, and adherence

Meets criteria for mild-to-moderate cognitive impairment with MMSE score of 14 through 26

Exclusion Criteria

Subject has a current diagnosis of a significant psychiatric illness per DSM-V

Other significant pathological findings on brain MRI

With glycosylated hemoglobin (HbA1c) ≥ 10 at screening

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive T3D-959 or placebo orally once a day

78 weeks

Regular visits for assessments

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• T3D-959

Trial Overview The trial is testing T3D-959, an oral medication that might help treat Alzheimer's. It will be given daily for 78 weeks and compared to a placebo to see if it's effective and safe, and whether it can alter the disease's progression.

How Is the Trial Designed?

Group I: 30mg T3D-959 Experimental Treatment 1 Intervention

Experimental: 30mg T3D-959 Arm Description: Experimental: T3D-959 30 mg dose: T3D-959 is a small molecule dual nuclear receptor agonist that regulates transcription of genes, in particular those involved in glucose energy and lipid metabolism. T3D-959 is 15-times more potent for PPAR delta than for the secondary target of the drug, PPAR gamma. The 15 mg strength contains 15mg T3D-959, pregelatinized starch NF, magnesium stearate NF, and size 0, hard gelatin, white/white, opaque, unmarked capsules. Subjects will ingest two size 0, 15mg capsules once per day in the morning.

Group II: Placebo, matching T3D-959 active capsules Placebo Group 1 Intervention

Placebo Comparator: Placebo, matching T3D-959 active capsules, is pregelatinized starch NF, magnesium stearate NF, and size 0, hard gelatin, white/white, opaque, unmarked capsules. Subjects randomized to placebo will ingest two size 0 placebo capsules once per day in the morning.

Who Is Running the Clinical Trial?

T3D Therapeutics, Inc.

Lead Sponsor

Trials

2

Recruited

290+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11713541/

Phase 2 PIONEER Trial of Oral T3D‐959 for the Treatment ... T3D‐959 demonstrated significant improvement over placebo in plasma Aβ42/40 ratio and in plasma neurogranin. Biomarkers of all three AD diagnostic criteria, ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT06964230

A Phase 2b/3 Clinical Study Evaluating T3D-959 in Mild-to- ... This study is a randomized, double-blind, placebo-controlled study of T3D-959 30mg in subjects with clinical mild-to-moderate Alzheimer's Disease and a ...

3. neurologylive.com neurologylive.com/view/alzheimer-agent-t3d-959-demonstrates-disease-modifying-effects-phase-2-pioneer-trial

Alzheimer Agent T3D-959 Demonstrates Disease ... The drug showed a strong safety profile and met primary endpoints, showing efficacy in slowing clinical and biological decline and supporting further ...

4. t3dtherapeutics.com t3dtherapeutics.com/lead-product-candidate-t3d-959/

Lead Product Candidate T3D-959 Preclinical studies in an experimental rat model of sporadic Alzheimer's disease, demonstrated that T3D-959 abrogated or reduced most of the AD ...

5. alzdiscovery.org alzdiscovery.org/uploads/cognitive_vitality_media/T3D-959.pdf

T3D-959 Alzheimer's disease T3D-959 has primarily been tested in a metabolic model of AD, where, as a metabolic modulator, it would be expected to be most efficacious.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5577391/

T3D-959: A Multi-Faceted Disease Remedial Drug Candidate ... T3D-959, a dual PPAR-δ/PPAR γ nuclear receptor agonist and former diabetes drug candidate, has been repositioned as an Alzheimer's disease (AD)-modifying ...

7. alz-journals.onlinelibrary.wiley.com alz-journals.onlinelibrary.wiley.com/doi/abs/10.1002/alz.064647

The PIONEER Study: A Multi‐center, Randomized, Double ... PIONEER is designed to evaluate the efficacy and safety of multiple dose strengths of T3D-959 in patients with mild to moderate severity AD.

8. t3dtherapeutics.com t3dtherapeutics.com/wp-content/uploads/2024/07/AAIC24_Poster_Final-1.pdf

Phase 2 PIONEER Trial of Oral T3D-959 for the Treatment ... multi-center trial evaluating efficacy and safety of the dual. PPARδ/γ agonist T3D-959 in patients with mild-to-moderate. Alzheimer's disease (AD). 250 ...