A Phase 2b/3 Clinical Study Evaluating T3D-959 in Mild-to-Moderate Alzheimer's Disease Subjects

NCT06964230 | Not Yet Recruiting Phase 2 FDA Drug

• 1 other identifier: T3D959-301
• Study Type: interventional
• Target: 376
• Locations: 1 country
• Sites: 1

Brief Summary

This study is a Phase 2b/3 clinical trial of a new candidate drug (T3D-959) to treat patients with mild-to-moderate Alzheimer's. The aims of the trial are to affirm potential therapeutic efficacy and safety observed in earlier clinical trials and assess the potential to modify the course of disease. The drug will be compared to placebo and administered orally to patients once a day for 78 weeks.

Conditions

Alzheimer's Disease

Keywords

T3D-959; Mild-to-Moderate Alzheimer's Disease Severity; New Drug Treatment Being Tested; Once-a-day oral drug administration; Phase 2b/3 Study T3D959-301; Brain Metabolism

Outcome Measures

Primary Outcomes (1)

• Change from baseline to end of treatment in ADAS-Cog13 and ADCS-iADL

  Primary Efficacy Endpoint • Co-primary endpoints of Alzheimer's Disease Assessment Scale cognitive subscale, 13-items (ADAS-Cog13) with a score range of 0-85 (higher scores indicating greater dysfunction) and Alzheimer's Disease Cooperative Study Instrumental Activities of Daily Living (ADCS-iADL) with a score range of 0-56 (lower scores indicating worse performance), in subjects with a clinical diagnosis of mild-to-moderate AD and biological diagnosis of AD pathology. ADAS-cog 13

  78 weeks

Secondary Outcomes (4)

• Change from Baseline to End of Treatment in plasma AB42/40 ratio, in subjects with a clinical diagnosis of mild-to-moderate AD and biological diagnosis of AD pathology

  78 weeks

• Change from Baseline to End of Treatment in disease stage progression on the Clinical Dementia Rating Scale-Global (CDR-Global), in subjects with a clinical diagnosis of mild-to-moderate AD and biological diagnosis of AD pathology

  78 weeks

• Change from baseline to end of treatment in Clinical Dementia Rating Scale - Sum of Boxes (CDR-SB), in subjects with a clinical diagnosis of mild-to-moderate AD and biological diagnosis of AD pathology

  78 weeks

• Change from Baseline to End of Treatment on the integrated Alzheimer's Disease Rating Scale (iADRS), in subjects with a clinical diagnosis of mild-to-moderate AD and biological diagnosis of AD pathology

  78 weeks

Other Outcomes (1)

• Additional Endpoints (Exploratory) • Change from Baseline to End of Treatment in plasma proteomic biomarker levels (i.e. Neurogranin, GFAP, MTBR-243)

  78 weeks

Study Arms (2)

Placebo, matching T3D-959 active capsules

PLACEBO COMPARATOR

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.

Other: Placebo Comparator

30mg T3D-959

EXPERIMENTAL

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.

Drug: T3D-959

Interventions

T3D-959 DRUG

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 capsules contain 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.

30mg T3D-959

Placebo Comparator OTHER

Placebo used to compare to T3D-959 drug

Placebo, matching T3D-959 active capsules

Eligibility Criteria

• Age: 50 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female subject aged 50-90 years old inclusive at the time of Informed Consent
• Subject (or legal representative) and caregiver must sign an Informed Consent to participate in the study.
• Subject has a caregiver, an identified adult who, in the opinion of the investigator, has sufficient contact to knowledgeably report on the subject's cognition, function, behavior, safety, compliance and adherence. Same caregiver should, whenever possible, assist the subject throughout the duration of the trial
• Subject has a biological diagnosis of AD pathology, as assessed by a validated plasma biomarker (presently %p-tau217 plasma biomarker), according to the NIA-AA (National Institute of Aging - Alzheimer's Association) criteria at screening
• Subject has a clinical diagnosis of mild to moderate AD (Stage 4 or 5) according to the NIA-AA (National Institute of Aging - Alzheimer's Association) criteria at screening
• Meets criteria for mild-to-moderate cognitive impairment with Mini-Mental State Examination (MMSE) score of 14 through 26 at the screening visit.
• Modified Hachinski \< 4 at screening
• Clinical Dementia Rating is 0.5 to 2.0 at screening
• Visual and auditory acuity adequate for neuropsychological testing
• Medical stability for this study as confirmed by review of records, comprehensive physical exam, neurological exam, and laboratory tests

You may not qualify if:

• Able to swallow oral medications
• Subject has a current diagnosis of a significant psychiatric illness per the Diagnostic and Statistical Manual of Mental Disorders V (DSM-V) including but not limited to major depressive disorder, anxiety disorders and is in an acute phase/episode; or the subject has a current diagnosis or history of schizophrenia or bipolar disorder; or has current signs of suicidality or history of suicide attempt
• Subject with untreated clinical depression at screening; Geriatric Depression Scale (GDS) Short Form \> 9
• Evidence of clinically significant lesion(s) on brain MRI at Screening that could indicate a dementia diagnosis other than Alzheimer's disease
• Subject has a current diagnosis of a neurological disease other than AD, which has or could result in cognitive impairment, including, but not limited to, any of the following:
• History of clinically significant stroke or multiple strokes as ascertained by history and/or brain imaging findings, or history of TIA's within 12 months prior to baseline
• History of serious brain infection
• History of or current space occupying cerebral lesion
• History of clinically significant concussion or repeated head trauma associated with sustained cognitive impairment in the last 5 years
• Huntington's Disease
• Parkinson's Disease
• Dementia predominantly of a non-Alzheimer's type (vascular dementia, frontotemporal dementia, Parkinson's dementia, substance-induced dementia)
• Normal pressure hydrocephalus
• History of seizures (except for childhood febrile) or epilepsy
• With glycosylated hemoglobin (HbA1c) ≥ 10 at screening

Sponsors & Collaborators

• T3D Therapeutics, Inc.: lead

Study Sites (1)

T3D Therapeutics, Inc.

Durham, North Carolina, 27713, United States

Location

MeSH Terms

Conditions

Alzheimer Disease

Condition Hierarchy (Ancestors)

Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders

Study Officials

• John Didsbury, Chief Executive Officer, Ph.D

  T3D Therapeutics, Inc.

  STUDY DIRECTOR

Central Study Contacts

Blake E Swearingen, MS

CONTACT

919-622-3409; blakeswearingen@t3dtherapeutics.com

John Didsbury, Ph.D., Chief Executive Officer

CONTACT

919-237-4897; johndidsbury@t3dtherapeutics.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chief Executive Officer

Study Record Dates

• First Submitted: April 14, 2025
• First Posted: May 9, 2025
• Study Start (Estimated): October 26, 2026
• Primary Completion (Estimated): April 1, 2031
• Study Completion (Estimated): June 1, 2031
• Last Updated: May 9, 2025

Record last verified: 2025-04

Locations

US (1)