Clinical Study Evaluating Efficacy and Safety of T3D-959 in Mild-to-moderate AD Subjects

NCT04251182 | Completed Phase 2 DMC FDA Drug

• 2 other identifiers: T3D959-2021R01AG061122
• Study Type: interventional
• Target: 250
• Locations: 1 country
• Sites: 1

Brief Summary

A Randomized, Double-Blind, Placebo-Controlled Multi-Center Study to Evaluate the Safety and Efficacy of Three Dose Strengths of T3D-959 in Subjects with Mild-to-Moderate Alzheimer's Disease.

Conditions

Alzheimer Disease

Keywords

mild-to-moderate Alzheimer Disease

Outcome Measures

Primary Outcomes (3)

• Efficacy of T3D-959 on cognition

  Change in cognition as assessed by The Alzheimer's Disease Assessment Scale 11-task cognitive subscale (ADAS-Cog11) from baseline to end of treatment visit, compared to placebo

  28 weeks (Subjects are on active treatment for 24 weeks followed by a 4-week follow-up)

• Efficacy of T3D-959 on function

  Change in global function as assessed by Alzheimer's Disease Cooperative Study Clinical Global Impression of Change (ADCS-CGIC) from baseline to end of treatment visit, compared to placebo

  28 weeks (Subjects are on active treatment for 24 weeks followed by a 4-week follow-up)

• Safety and tolerability of T3D-959

  Safety will be assessed by 1) AEs, clinical labs, ECG, weight, vital signs 2) Geriatric Depression Scale (GDS) 3)Columbia Suicide Severity Rating Scale (C-SSRS)

  28 weeks (Subjects are on active treatment for 24 weeks followed by a 4-week follow-up)

Secondary Outcomes (2)

• Efficacy of T3D-959 on executive function

  28 weeks (Subjects are on active treatment for 24 weeks followed by a 4-week follow-up)

• Efficacy of T3D-959 on plasma Aβ 42/40 ratio biomarker level

  28 weeks (Subjects are on active treatment for 24 weeks followed by a 4-week follow-up)

Study Arms (4)

Placebo

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 three size 0 placebo capsules once per day in the morning.

Drug: Placebos

15mg T3D-959

EXPERIMENTAL

T3D-959 15 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 one size 0, 15mg capsule and two placebo capsules once per day in the morning.

Drug: 15mg T3D-959

30mg T3D-959

EXPERIMENTAL

T3D-959 30 mg dose: Subjects will ingest two size 0, 15mg capsules and one placebo capsule once per day in the morning.

Drug: 30 mg T3D-959

45mg T3D-959

EXPERIMENTAL

T3D-959 45 mg dose: Subjects will ingest three size 0, 15mg capsules once per day in the morning.

Drug: 45 mg T3D-959

Interventions

15mg T3D-959 DRUG

Oral administration once daily in the morning

Also known as: T3D-959

15mg T3D-959

30 mg T3D-959 DRUG

Oral administration once daily in the morning

Also known as: T3D-959

30mg T3D-959

45 mg T3D-959 DRUG

Oral administration once daily in the morning

Also known as: T3D-959

45mg T3D-959

Placebos DRUG

Oral administration once daily in the morning

Also known as: T3D-959 Placebo

Placebo

Eligibility Criteria

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

You may qualify if:

• Have a reliable caregiver, an identified adult who, in the opinion of the investigator has sufficient contact to knowledgeably report on the subject's daily cognition, function, behavior, safety, compliance and adherence. Same caregiver(s) must assist the subject throughout the duration of the trial.
• Have 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
• Meet criteria for mild-to-moderate cognitive impairment with Mini-Mental State Examination (MMSE) score of 14 through 26 at the screening visit.
• Neuroimaging evidence consistent with the diagnosis of AD
• Modified Hachinski \</= 4 at screening
• Clinical Dementia Rating is 0.5 to 2.0 at screening and Clinical Dementia Rating - Sum of Boxes is ≥ 3 at screening
• Visual and auditory acuity adequate for neuropsychological testing
• No evidence of hepatic impairment or renal insufficiency

You may not qualify if:

• Have a current diagnosis of a significant psychiatric illness per the Diagnostic and Statistical Manual of Mental Disorders V (DSM-V)
• With untreated clinical depression (GDS \>/= 6 at screening and baseline)
• Have a current diagnosis of a neurological disease other than AD
• With glycosylated hemoglobin (HbA1c) \>/= 7.7 at screening
• With a diagnosis of unstable diabetes
• With clinically significant thyroid disease at screening TSH \>5
• Have any of the following values at the screening visit:
• ALT and/or AST value that is twice the upper limit of normal
• Total bilirubin value that exceeds 2 mg/dL
• Creatinine level \>1.5 mg/dL in men or \> 1.4 mg/dL in women
• Positive urinalysis (other than trace result) unless a cause other than renal impairment
• Glomerular filtration rate (GFR) values \<54 mL/min/1.73 m2
• Gamma-glutamyl transpeptidase (GGT) value that is twice the upper limit of normal
• Is positive for hepatitis B or anti-hepatitis C virus antibodies at the screening
• Have a history of moderate or severe congestive heart failure, NYHA class III or IV

Sponsors & Collaborators

• T3D Therapeutics, Inc.: lead
• National Institute on Aging (NIA): collaborator
• Clinilabs, Inc.: collaborator
• Alzheimer's Association: collaborator

Study Sites (1)

T3D Therapeutics

Durham, North Carolina, 27709, 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

• Blake Swearingen, MS

  T3D Therapeutics, Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Study drug packaging and labeling will maintain the double-blind design of the study. T3D-959 and placebo capsules will be identical in appearance. Therefore, the subject's treatment assignment will not be known to the subject or the study site personnel. None of the persons directly involved in the conduct of the study will have access to the treatment code. The DSMB and persons involved with reporting to the DSMB (as outlined within the DSMB Charter) will have access to the treatment code. The treatment code will be released to the study team after the study database has been locked.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: A randomized, double-blind, placebo-controlled design evaluating three dose levels (15 mg, 30 mg, 45 mg) of T3D-959 in subjects with mild-to-moderate Alzheimer's Disease. Subjects will be stratified by ApoE4 genotype and assigned to one of four dose groups (1:1:1:1 ratio) in a randomized fashion.

Study Record Dates

• First Submitted: January 24, 2020
• First Posted: January 31, 2020
• Study Start: March 1, 2021
• Primary Completion: January 20, 2023
• Study Completion: February 17, 2023
• Last Updated: July 19, 2024

Record last verified: 2024-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)