Moderate Alzheimer's Disease Clinical Trial
Official title:
A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel Design, Prospective, Phase IIa Clinical Trial to Evaluate the Safety and Efficacy of GV1001 Administered Subcutaneously for the Treatment of Moderate Alzheimer's Disease
The current study is being conducted by the Sponsor to evaluate the efficacy and safety of GV1001 (0.56 mg and 1.12 mg) administered subcutaneously as a treatment for moderate Alzheimer's disease (AD). GV1001 has been shown to inhibit neurotoxicity, apoptosis, and the production of reactive oxygen species induced by amyloid beta in neural stem cells by mimicking the extra-telomeric functions of human telomerase reverse transcriptase (hTERT). In nonclinical studies, using both mild (early stage) and severe (late stage) AD mouse models, GV1001 has been shown to improve cognitive function and memory, as well as significantly reduce the amount of amyloid beta and tau proteins. The multifunctional effect of GV1001 makes it a promising therapeutic option for the treatment for AD.
This is a multicenter, randomized, double-blind, placebo-controlled, dose finding, parallel-group Phase IIa study in participants with moderate AD. The study population will be comprised of male and female participants between 55 and 85 years of age, inclusive, with a diagnosis of probable AD based on National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association (NINCDS ADRDA) criteria. Participants must also meet Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-V) criteria for dementia and have an Mini-Mental State Examination (MMSE) score ≥10 to <20. Participants or their legal representative, as well as the participant's caregiver, must be able to provide written informed consent. The study will consist of a screening visit (up to 4 weeks prior to first dose), a 26-week double blind treatment period, and an end-of-study (EOS) visit. In the event a participant discontinues treatment or the study prematurely, the participant will be asked to return for an early termination (ET) visit for safety assessments. These assessments are the same as those done at the EOS visit. Prior to randomization, eligibility of potential participants will be confirmed through an adjudication process in which screening data (eg, MMSE) obtained to evaluate AD status are reviewed by a central independent adjudicator. The adjudicator will review the scoring sheet completed by the Investigator prior to randomization and provide an independent assessment of the participant's eligibility and may request exclusion of a participant from entry into the study. A central independent reader will review magnetic resonance imaging (MRI) or computed tomography (CT) scans or reports to confirm eligibility. Investigators must not randomize a participant prior to receipt of this independent confirmation of the participant's eligibility. Eligible participants will be randomized to treatment with either GV1001 0.56 mg, GV1001 1.12 mg, or placebo (normal saline) in a 1:1:1 ratio. Study treatment (GV1001 0.56 mg, GV1001 1.12 mg, or placebo) will be administered by subcutaneous (SC) injection every week for 4 weeks (4 times) followed by SC administration every 2 weeks through Week 24 (10 times) for a total of 14 SC administrations of study treatment. Efficacy evaluations will be performed at baseline, Week 12, and Week 26 using the Mini-Mental State Examination (MMSE), Alzheimer's Disease Assessment Scale-cognitive (ADAS cog), Clinician's Interview-Based Impression of Change (CIBIC)-Plus, Clinical Dementia Rating - Sum of Boxes (CDR-SB), Alzheimer's Disease Cooperative Study-Activities of Daily Living scale (ADCS-ADL), and Neuropsychiatric Inventory (NPI) scales. The efficacy evaluations are to be done in the same order at each visit. To ensure the objectivity and accuracy of the study results, efficacy evaluations must be performed by adequately trained and experienced clinicians. The raters must be certified for this study to administer the Mini-Mental State Examination (MMSE), Alzheimer's Disease Assessment Scale-cognitive (ADAS cog), Clinician's Interview-Based Impression of Change (CIBIC)-Plus, Clinical Dementia Rating - Sum of Boxes (CDR-SB), Alzheimer's Disease Cooperative Study-Activities of Daily Living scale (ADCS-ADL), and Neuropsychiatric Inventory (NPI) scales. Training, certification, and materials for rating will be provided by a rater training group. To mitigate the risk of breaking the blind, the efficacy evaluator is not to be involved in the participant's treatment or have access to the record of reported Adverse Events (AEs). Safety will be assessed throughout the study by monitoring for AEs, laboratory evaluations, electrocardiogram (ECG) findings, vital sign measurements, and suicidal ideation and behavior (C-SSRS). Pharmacodynamics will be evaluated by collecting blood and cerebrospinal fluid (CSF) for analysis of biomarkers of AD. Blood samples will also be collected for pharmacokinetic (PK) and immunogenicity analysis, including determination of GV1001 plasma concentrations (sparse PK) and antibodies to GV1001. ;
| Status | Clinical Trial | Phase | |
|---|---|---|---|
| Completed |
NCT00423228 -
Efficacy Study of a ZT-1 Implant in Patients Suffering From Alzheimer's Disease
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N/A |