A Study to Evaluate the Safety and Efficacy of CT1812 in Early Alzheimer's Disease

Study Overview
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Brief Summary
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This is a multicenter randomized, double-blind, placebo-controlled Phase 2 study designed to evaluate the efficacy, safety, and tolerability of two doses of CT1812 compared to placebo in participants diagnosed with early Alzheimer's disease.

Detailed Description
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This is a multicenter randomized, double-blind, placebo-controlled Phase 2 study designed to evaluate the efficacy, safety, and tolerability of two doses of CT1812 compared to placebo for approximately 18 months (72 weeks) in approximately 540 participants diagnosed with early Alzheimer's disease Participants will be randomized 1:1:1 to receive either 100mg or 200mg of CT1812 or placebo. CT1812 or placebo will be administered as 2 capsules to be taken orally once daily.

Official Title
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Synaptic Therapy Alzheimer's Research Trial (START): A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Trial to Evaluate the Safety and Efficacy of CT1812 in Early Alzheimer's Disease Over 18 Months.

Conditions
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Early Alzheimer's Disease

Intervention / Treatment
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* Drug: CT1812
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Ages 50-85 years. Diagnosis of either MCI due to AD or mild AD dementia. MMSE 20-30 (inclusive). Amyloid PET scan of the brain or CSF biomarkers consistent with AD. Neuroimaging (MRI) obtained during screening consistent with the clinical diagnosis of Alzheimer's disease, as based on central read. Exclusion Criteria: Screening MRI of the brain indicative of significant abnormality. Clinically significant abnormalities in screening laboratory tests. Clinical or laboratory findings consistent with: Other primary degenerative dementia, (dementia with Lewy bodies, fronto-temporal dementia, Huntington's disease, Creutzfeldt-Jakob Disease, Down syndrome, etc.). Other neurodegenerative condition (Parkinson's disease, amyotrophic lateral sclerosis, etc.). Other infectious, metabolic or systemic diseases affecting the central nervous system (syphilis, present hypothyroidism, present vitamin B12, other laboratory values etc.) A participant known to be actively infected with hepatitis B or hepatitis C at screening. History of acute/chronic hepatitis B or C and/or carriers of hepatitis B (seropositive for hepatitis B surface antigen [HbsAg] or anti-hepatitis C [HCV] antibody). Participants who have evidence of resolved hepatitis infection (e.g., HCV RNA negative) may be considered following discussion with the Medical Monitor. A current DSM-V diagnosis of active major depression or GDS > 6, schizophrenia, or bipolar disorder.

Ages Eligible for Study
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Minimum Age: 50 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: CT1812 100 mg<br>CT1812 at a dose of 100 n=180 group | Drug: CT1812<br>* Study Drug<br>* Other names: Study Drug Active;|
| Active Comparator: CT1812 200 mg<br>CT1812 at a dose of 300mg, n=180 group | Drug: CT1812<br>* Study Drug<br>* Other names: Study Drug Active;|
| Placebo Comparator: Placebo<br>Placebo, n=180 group | Drug: Placebo<br>* Non-active study drug<br>* Other names: Matching Placebo;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in the Clinical Dementia Rating Scale Sum of Boxes (CDR-SB) scale. | The Clinical Dementia Rating (CDR) is a clinical scale that describes 5 levels of impairment in performance on each of 6 categories of function including memory, orientation, judgment and problem solving, community affairs, home and hobbies, and personal care. The ratings of degree of impairment obtained on each of the 6 categories of function are synthesized into 1 global rating of dementia as absent, questionable, mild, moderate, or severe (global CDR scores of 0, 0.5, 1, 2, or 3, respectively). The score is based on interviews with the participant and study partner, using a structured interview. A sum of boxes score (CDR-SB) provides an additional measure of change where each category has a maximum possible score of 3 points and the total score is a sum of the category scores giving a total possible score of 0 to 18 with higher scores indicating more impairment. | 18 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Alzheimer's Disease Assessment Scale-Cognition (ADAS-Cog 13) | Change from baseline in the Alzheimer's Disease Assessment Scale-Cognition (ADAS-Cog 13) at 18 months. | 18 months | 
| Alzheimer's Disease Cooperative Study - Activities of Daily Living Scale (ADCS - ADL) in people with Mild Cognitive Impairment (MCI) - ADCS-ADL-MCI. | Change from baseline in the Alzheimer's Disease Cooperative Study - Activities of Daily Living Scale (ADCS - ADL) in people with Mild Cognitive Impairment (MCI) - ADCS-ADL-MCI at 18 months. | 18 months | 
| Cerebrospinal fluid (CSF) concentrations of beta-amyloid (Aβ) 40 and 42, tau, phospho-tau (ptau), neurofilament light (NfL), neurogranin, and synaptotagmin. | Change from baseline at 18 months. | 18 months | 
| Plasma measures of Aβ fragments, ptau, and Neurofilament light (NfL) | Change from baseline at 18 months. | 18 months | 
| Volumetric Magnetic Resonance Imaging (MRI) including hippocampal and whole brain volume change | Change from baseline at 18 months. | 18 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Alzheimer's Disease