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
Overview
- Phase
- Phase 2
- Intervention
- Placebos
- Conditions
- Alzheimer Disease
- Sponsor
- T3D Therapeutics, Inc.
- Enrollment
- 250
- Locations
- 1
- Primary Endpoint
- Efficacy of T3D-959 on cognition
- Status
- Completed
- Last Updated
- last year
Overview
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.
Detailed Description
Study Design \& Methods: Phase 2 multi-center, randomized, double blind, placebo-controlled study of T3D959 15 mg, 30 mg, 45 mg, or matching placebo administered orally once daily for 24 weeks. There will be equal allocation of subject numbers across the four groups. Stratified randomization will be conducted on the basis of ApoE4 genotype so that subjects are randomized into one of the four dose groups within each stratum of ApoE4 status: ApoE4-positive (at least one E4 allele) vs ApoE4-negative (no E4 alleles). Following informed consent, subjects will enter the screening phase of the study. Once eligibility is confirmed and before the start of the first dose of study drug, subjects will be randomized on a 1:1:1:1 basis to placebo or T3D959 treatment (15mg, 30mg, 45mg) for the 24-week treatment period. Investigators, subjects, and caregivers will be blinded to the treatment assignment. Study schedule visits: screening, baseline, weeks 4, 8, 16, 24 and 28 (F/U visit)
Investigators
Eligibility Criteria
Inclusion Criteria
- •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
Exclusion Criteria
- •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
Arms & Interventions
Placebo
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.
Intervention: Placebos
15mg T3D-959
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.
Intervention: 15mg T3D-959
30mg T3D-959
T3D-959 30 mg dose: Subjects will ingest two size 0, 15mg capsules and one placebo capsule once per day in the morning.
Intervention: 30 mg T3D-959
45mg T3D-959
T3D-959 45 mg dose: Subjects will ingest three size 0, 15mg capsules once per day in the morning.
Intervention: 45 mg T3D-959
Outcomes
Primary Outcomes
Efficacy of T3D-959 on cognition
Time Frame: 28 weeks (Subjects are on active treatment for 24 weeks followed by a 4-week follow-up)
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
Efficacy of T3D-959 on function
Time Frame: 28 weeks (Subjects are on active treatment for 24 weeks followed by a 4-week follow-up)
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
Safety and tolerability of T3D-959
Time Frame: 28 weeks (Subjects are on active treatment for 24 weeks followed by a 4-week follow-up)
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)
Secondary Outcomes
- 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))