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

T3D Therapeutics

Status and phase

Completed

Phase 2

Conditions

Alzheimer Disease

Treatments

Drug: 15mg T3D-959

Drug: 30 mg T3D-959

Drug: Placebos

Drug: 45 mg T3D-959

Study type

Interventional

Funder types

Other

Industry

NIH

Identifiers

NCT04251182

1R01AG061122 (U.S. NIH Grant/Contract)

T3D959-202

Details and patient eligibility

About

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.

Full 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)

Enrollment

250 patients

Sex

All

Ages

50 to 90 years old

Volunteers

No Healthy Volunteers

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
- 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
Have experienced a previous cardiovascular event (myocardial infarct, by-pass surgery, or PTCA) within the past 12 months prior to the baseline
Have blood pressure reading at screening that is greater than 160/100 mmHg
Have a clinically significant unstable illness
Have a history of HIV infection
Have a history of alcohol, drug abuse or dependence
Have a history of cancer within 5 years of the screening
Have any surgical or medical condition which may significantly alter the absorption of any drug substance
Females who are pregnant, nursing or of childbearing potential and not practicing effective contraception
Is required to take excluded medications as specified protocol
Have a known or suspected intolerance or hypersensitivity to the study drug, closely related compounds
Resides in hospital or moderate to high dependency continuous care facility
Are non-ambulatory, or wheelchair-bound
Have evidence of clinically relevant pathology that in the investigator's opinion could interfere with the study results or put the subject's safety at risk
History of swallowing difficulties

Trial design

Primary purpose

Treatment

Allocation

Randomized

Interventional model

Parallel Assignment

Masking

Quadruple Blind

250 participants in 4 patient groups, including a placebo group

Placebo

Placebo Comparator group

Description:

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.

Treatment:

Drug: Placebos

15mg T3D-959

Experimental group

Description:

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.

Treatment:

Drug: 15mg T3D-959

30mg T3D-959

Experimental group

Description:

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

Treatment:

Drug: 30 mg T3D-959

45mg T3D-959

Experimental group

Description:

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