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

Alzheimer Disease Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04251182
• Other study ID #: T3D959-202
• Secondary ID: 1R01AG061122
• Status: Completed
• Phase: Phase 2
• Start date: March 1, 2021
• Est. completion date: February 17, 2023

Study information

• Verified date: February 2023
• Source: T3D Therapeutics, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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)

Recruitment information / eligibility

• Status: Completed
• Enrollment: 250
• Est. completion date: February 17, 2023
• Est. primary completion date: January 20, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 50 Years to 90 Years

Eligibility

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

Related Conditions & MeSH terms

• Alzheimer Disease

Intervention

Drug:
• 15mg T3D-959
Oral administration once daily in the morning
• 30 mg T3D-959
Oral administration once daily in the morning
• 45 mg T3D-959
Oral administration once daily in the morning
• Placebos
Oral administration once daily in the morning

Locations

Country	Name	City	State
United States	Dent Neurologic Institute	Amherst	New York
United States	Community Hospital of Anderson and Madison County Inc.	Anderson	Indiana
United States	American health Network-Avon	Avon	Indiana
United States	PharmaSite Research	Baltimore	Maryland
United States	Integrative Clinical Trials, LLC	Brooklyn	New York
United States	ANI Neurology, PLLC dba Alzheimer's Memory Center	Charlotte	North Carolina
United States	New Hope Clinical Research	Charlotte	North Carolina
United States	iResearch Atlanta	Decatur	Georgia
United States	Mile High Research Center	Denver	Colorado
United States	Clarity Clinical Research	East Syracuse	New York
United States	Center for Advanced Research & Education	Gainesville	Georgia
United States	Indago Research and Health Center	Hialeah	Florida
United States	Infinity Clinical Research	Hollywood	Florida
United States	Hawaii Pacific Neuroscience	Honolulu	Hawaii
United States	Clinical Trial Network	Houston	Texas
United States	Charter Research - Lady Lake	Lady Lake	Florida
United States	Neurology Center of Las Vegas	Las Vegas	Nevada
United States	ClinCloud, LLC	Maitland	Florida
United States	Merritt Island Medical Research, LLC	Merritt Island	Florida
United States	Allied Biomedical Research Institute	Miami	Florida
United States	CCM Clinical Research Group	Miami	Florida
United States	Elite Clinical Research	Miami	Florida
United States	Global Life Research	Miami	Florida
United States	Health Care Family Rehab and Research Center	Miami	Florida
United States	Miami Dade Medical Research Institute, LLC	Miami	Florida
United States	Miami Jewish Health	Miami	Florida
United States	Premier Clinical Research Institute, Inc.	Miami	Florida
United States	The Neurology Research Group	Miami	Florida
United States	Visionary Investigators Network	Miami	Florida
United States	Suncoast Clinical Research	New Port Richey	Florida
United States	Manhattan Behavioral Medicine	New York	New York
United States	Research Center for Clinical Studies	Norwalk	Connecticut
United States	Headlands Research Orlando	Orlando	Florida
United States	Advanced Research Consultants	Palm Beach Gardens	Florida
United States	IMIC Research	Palmetto Bay	Florida
United States	National Research Institute	Panorama City	California
United States	Visionary Investigators Network	Pembroke Pines	Florida
United States	Cognitive Clinical Trials, LLC	Phoenix	Arizona
United States	Pacific Research Network	San Diego	California
United States	CITrials	Santa Ana	California
United States	Syrentis Clinical Research	Santa Ana	California
United States	Imaging Endpoints	Scottsdale	Arizona
United States	Richmond Behavioral Associates	Staten Island	New York
United States	Mercury Clinical Research	Sugar Land	Texas
United States	Palmetto Clinical Research	Summerville	South Carolina
United States	Santos Research Center	Tampa	Florida
United States	Central States Research, LLC	Tulsa	Oklahoma
United States	ClinCloud Clinical Research	Viera	Florida

Sponsors (4)

Lead Sponsor	Collaborator
T3D Therapeutics, Inc.	Alzheimer's Association, Clinilabs, Inc., National Institute on Aging (NIA)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)
Primary	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)
Primary	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	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)
Secondary	Efficacy of T3D-959 on plasma Aß 42/40 ratio biomarker level	Change in Aß 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)