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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04251182
Recruitment Status : Suspended (COVID-19 Panemic)
First Posted : January 31, 2020
Last Update Posted : October 22, 2020
Sponsor:
Collaborators:
National Institute on Aging (NIA)
Clinilabs, Inc.
Information provided by (Responsible Party):
T3D Therapeutics, Inc.

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.

Condition or disease Intervention/treatment Phase
Alzheimer Disease Drug: 15mg T3D-959 Drug: 30 mg T3D-959 Drug: 45 mg T3D-959 Drug: Placebos Phase 2

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)

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 256 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
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.
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description: 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.
Primary Purpose: Treatment
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
Estimated Study Start Date : February 2021
Estimated Primary Completion Date : September 2022
Estimated Study Completion Date : September 2022


Arm Intervention/treatment
Placebo Comparator: 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.
Drug: Placebos
Oral administration once daily in the morning
Other Name: T3D-959 Placebo

Experimental: 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.
Drug: 15mg T3D-959
Oral administration once daily in the morning
Other Name: T3D-959

Experimental: 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.
Drug: 30 mg T3D-959
Oral administration once daily in the morning
Other Name: T3D-959

Experimental: 45mg T3D-959
T3D-959 45 mg dose: Subjects will ingest three size 0, 15mg capsules once per day in the morning.
Drug: 45 mg T3D-959
Oral administration once daily in the morning
Other Name: T3D-959




Primary Outcome Measures :
  1. 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

  2. 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

  3. 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 Outcome Measures :
  1. Efficacy of T3D-959 on executive function [ Time Frame: 28 weeks (Subjects are on active treatment for 24 weeks followed by a 4-week follow-up) ]
    Change in executive function as assessed by the Digit Symbol Coding Test (DSCT) from baseline to end of treatment visit, compared to placebo

  2. Efficacy of T3D-959 on plasma Aβ 42/40 ratio biomarker level [ Time Frame: 28 weeks (Subjects are on active treatment for 24 weeks followed by a 4-week follow-up) ]
    Change in Aβ 42/40 ratio plasma biomarker from baseline to end of treatment visit, compared to placebo



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   50 Years to 90 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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 16 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
  • 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 <60 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04251182


Locations
Show Show 38 study locations
Sponsors and Collaborators
T3D Therapeutics, Inc.
National Institute on Aging (NIA)
Clinilabs, Inc.
Investigators
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Study Director: Hoda Gabriel, BS T3D Therapeutics, Inc.
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Responsible Party: T3D Therapeutics, Inc.
ClinicalTrials.gov Identifier: NCT04251182    
Other Study ID Numbers: T3D959-202
1R01AG061122 ( U.S. NIH Grant/Contract )
First Posted: January 31, 2020    Key Record Dates
Last Update Posted: October 22, 2020
Last Verified: June 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: A Clinical Study Report (CSR) will be generated within 9 months after database lock. Aggregate study data will be made available in this report.

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by T3D Therapeutics, Inc.:
mild-to-moderate Alzheimer Disease
Additional relevant MeSH terms:
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Alzheimer Disease
Dementia
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Tauopathies
Neurodegenerative Diseases
Neurocognitive Disorders
Mental Disorders