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

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

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 Overview

• Status: Completed
• Conditions: Alzheimer Disease
• Intervention / Treatment: Drug: Placebos; Drug: 15mg T3D-959; Drug: 30 mg T3D-959; Drug: 45 mg T3D-959

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)

• Study Type: Interventional
• Enrollment (Actual): 250
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Phoenix, Arizona, United States, 85048
      • Cognitive Clinical Trials, LLC
    • Scottsdale, Arizona, United States, 85258
      • Imaging Endpoints
  • California
    • Panorama City, California, United States, 91402
      • National Research Institute
    • San Diego, California, United States, 92065
      • Pacific Research Network
    • Santa Ana, California, United States, 92705
      • Syrentis Clinical Research
    • Santa Ana, California, United States, 92705
      • CITrials
  • Colorado
    • Denver, Colorado, United States, 80218
      • Mile High Research Center
  • Connecticut
    • Norwalk, Connecticut, United States, 06851
      • Research Center for Clinical Studies
  • Florida
    • Hialeah, Florida, United States, 33012
      • Indago Research and Health Center
    • Hollywood, Florida, United States, 33024
      • Infinity Clinical Research
    • Lady Lake, Florida, United States, 32159
      • Charter Research - Lady Lake
    • Maitland, Florida, United States, 32751
      • ClinCloud, LLC
    • Merritt Island, Florida, United States, 32952
      • Merritt Island Medical Research, LLC
    • Miami, Florida, United States, 33144
      • Elite Clinical Research
    • Miami, Florida, United States, 33133
      • Visionary Investigators Network
    • Miami, Florida, United States, 33133
      • CCM Clinical Research Group
    • Miami, Florida, United States, 33155
      • Allied Biomedical Research Institute
    • Miami, Florida, United States, 33176
      • Miami Dade Medical Research Institute, LLC
    • Miami, Florida, United States, 33122
      • Premier Clinical Research Institute, Inc.
    • Miami, Florida, United States, 33137
      • Miami Jewish Health
    • Miami, Florida, United States, 33176
      • The Neurology Research Group
    • Miami, Florida, United States, 33015
      • Health Care Family Rehab and Research Center
    • Miami, Florida, United States, 33155
      • Global Life Research
    • New Port Richey, Florida, United States, 34652
      • Suncoast Clinical Research
    • Orlando, Florida, United States, 32819
      • Headlands Research Orlando
    • Palm Beach Gardens, Florida, United States, 33410
      • Advanced Research Consultants
    • Palmetto Bay, Florida, United States, 33157
      • IMIC Research
    • Pembroke Pines, Florida, United States, 33026
      • Visionary Investigators Network
    • Tampa, Florida, United States, 33615
      • Santos Research Center
    • Viera, Florida, United States, 32940
      • ClinCloud Clinical Research
  • Georgia
    • Decatur, Georgia, United States, 30030
      • iResearch Atlanta
    • Gainesville, Georgia, United States, 30501
      • Center for Advanced Research & Education
  • Hawaii
    • Honolulu, Hawaii, United States, 96817
      • Hawaii Pacific Neuroscience
  • Indiana
    • Anderson, Indiana, United States, 46011
      • Community Hospital of Anderson and Madison County Inc.
    • Avon, Indiana, United States, 46123
      • American health Network-Avon
  • Maryland
    • Baltimore, Maryland, United States, 21208
      • PharmaSite Research
  • Nevada
    • Las Vegas, Nevada, United States, 89128
      • Neurology Center of Las Vegas
  • New York
    • Amherst, New York, United States, 14226
      • Dent Neurologic Institute
    • Brooklyn, New York, United States, 11229
      • Integrative Clinical Trials, LLC
    • East Syracuse, New York, United States, 13057
      • Clarity Clinical Research
    • New York, New York, United States, 10036
      • Manhattan Behavioral Medicine
    • Staten Island, New York, United States, 10314
      • Richmond Behavioral Associates
  • North Carolina
    • Charlotte, North Carolina, United States, 28270
      • ANI Neurology, PLLC dba Alzheimer's Memory Center
    • Charlotte, North Carolina, United States, 28211
      • New Hope Clinical Research
  • Oklahoma
    • Tulsa, Oklahoma, United States, 74136
      • Central States Research, LLC
  • South Carolina
    • Summerville, South Carolina, United States, 29485
      • Palmetto Clinical Research
  • Texas
    • Houston, Texas, United States, 77074
      • Clinical Trial Network
    • Sugar Land, Texas, United States, 77478
      • Mercury Clinical Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years to 90 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / 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 Names: 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 Names: 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 Names: 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 Names: T3D-959

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Efficacy of T3D-959 on executive function	Change in executive function as assessed by the Digit Symbol Coding Test (DSCT) 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 plasma Aβ 42/40 ratio biomarker level	Change in Aβ 42/40 ratio plasma biomarker 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)

Collaborators and Investigators

• Sponsor: T3D Therapeutics, Inc.
• Collaborators: National Institute on Aging (NIA); Alzheimer's Association; Clinilabs, Inc.
• Investigators: Study Director: Blake Swearingen, MS, T3D Therapeutics, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2021
• Primary Completion (Actual): January 20, 2023
• Study Completion (Actual): February 17, 2023

Study Registration Dates

• First Submitted: January 24, 2020
• First Submitted That Met QC Criteria: January 29, 2020
• First Posted (Actual): January 31, 2020

Study Record Updates

• Last Update Posted (Estimate): February 21, 2023
• Last Update Submitted That Met QC Criteria: February 17, 2023
• Last Verified: February 1, 2023

More Information

Terms related to this study

• Keywords: mild-to-moderate Alzheimer Disease
• Additional Relevant MeSH Terms: Mental Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Neurodegenerative Diseases; Dementia; Tauopathies; Alzheimer Disease
• Other Study ID Numbers: T3D959-202; 1R01AG061122 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD 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.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No