Clinical trial NCT04251182: Clinical Study Evaluating Efficacy and Safety of T3D-959 in Mild-to-moderate AD Subjects
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Alzheimer Disease
Keywords: mild-to-moderate Alzheimer Disease
Lead sponsor: T3D Therapeutics, Inc.
Sponsor class: INDUSTRY
Collaborators: name: National Institute on Aging (NIA)
name: Clinilabs, Inc.
name: Alzheimer's Association
First posted: 2020-01-31
Enrollment: 250
Sex: ALL
Minimum age (years): 50
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: 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.
Primary purpose: TREATMENT

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)

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
  * 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

Primary outcomes:
measure: Efficacy of T3D-959 on cognition
timeFrame: 28 weeks (Subjects are on active treatment for 24 weeks followed by a 4-week follow-up)
measure: Efficacy of T3D-959 on function
timeFrame: 28 weeks (Subjects are on active treatment for 24 weeks followed by a 4-week follow-up)
measure: Safety and tolerability of T3D-959
timeFrame: 28 weeks (Subjects are on active treatment for 24 weeks followed by a 4-week follow-up)
Secondary outcomes:
measure: Efficacy of T3D-959 on executive function
timeFrame: 28 weeks (Subjects are on active treatment for 24 weeks followed by a 4-week follow-up)
measure: Efficacy of T3D-959 on plasma Aβ 42/40 ratio biomarker level
timeFrame: 28 weeks (Subjects are on active treatment for 24 weeks followed by a 4-week follow-up)
Other outcomes:
Locations:
city: Durham
country: United States
facility: T3D Therapeutics
state: North Carolina
Study officials:
affiliation: T3D Therapeutics, Inc.
name: Blake Swearingen, MS
role: STUDY_DIRECTOR
References: