Clinical Trial to Evaluate the Efficacy and Safety of GV1001 in Alzheimer Patients

Study Overview
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Brief Summary
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This clinical study is designed as a multi-center, randomized, double-blind, placebo-controlled, parallel design, prospective, phase II clinical trial. An eligible subject who meets inclusion and exclusion criteria is randomly assigned to three groups: study group 1 (GV1001 0.56 mg), study group 2 (GV1001 1.12 mg) or placebo group. A randomized subject is administered either GV1001 or placebo in a total of 14 times and will be evaluated for the efficacy and safety at week of 24.

Detailed Description
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GV1001 0.56 mg, 1.12 mg or placebo is subcutaneously administered once weekly schedule for 4 weeks (4 times) followed by every two weeks until week 24 (10 times). A total number of administration is 14 times. Control group (placebo): 30 subjects Study group 1 (GV1001 0.56 mg): 30 subjects Study group 2 (GV1001 1.12 mg): 30 subjects.

Official Title
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A Multi-center, Randomized, Double-blind, Placebo-controlled, Parallel Design, Prospective, Phase II Clinical Trial to Evaluate the Efficacy and Safety of Donepezil and Combined With GV1001 in Alzheimer Patients

Conditions
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Alzheimer Disease

Intervention / Treatment
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* Drug: Normal Saline 0.9%
* Drug: GV1001 0.56 mg
* Drug: GV1001 1.12 mg


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 55 to 85 years of age A patient who satisfies diagnostic criteria for dementia in DSM-IV Probable Alzheimer's disease in NINCDS-ADRDA K-MMSE ≤ 19 at screening and randomization visit GDS 5 6 stage MRI or CT scan within 12 months prior to screening visit that proves Alzheimer's disease without any other disease that may cause dementia A patient taking stable doses of donepezil for more than 3 months before screening visit A patient who are able to visit a hospital (including inpatient and outpatient based) and receive cognitive and other tests A patient with a caregiver who can accompany all visits and supervise the subject's compliance with the procedures and study drug prescribed in the protocol, and provide detailed information about the patient Written informed consent by a patient or legal representative Exclusion Criteria: Any other cause of dementia shown by CT / MRI findings and neurological examination within 12 months of screening visit Possible, probable or definite vascular dementia according to the NINDS-AIREN Other central nervous system diseases that may cause cognitive impairment (cerebrovascular disease including cerebrovascular dementia, Parkinsonism, Huntington's disease, subdural hematoma, normal pressure hydrocephalus, brain tumor, Creutzfeldt-Jakob disease, etc.) Neurological deficits such as delusions, delirium, epilepsy Vitamin B12, folic acid, syphilis serology, and thyroid stimulating hormone (TSH) results are thought to contribute to the severity of dementia or cause dementia A patient who are considered ineligible for this study by investigator due to concurrent or history of significant psychiatric conditions (eg. schizophrenia or bipolar affective disorder) A patient with a history of known or suspected seizures including febrile seizures, a history of significant head trauma with loss of consciousness or recent unconsciousness that is not explained A patient with acute or unstable cardiovascular disease, active peptic ulcer, uncontrolled hypertension, uncontrolled diabetes or insulin dependent patients or any medical condition that may interfere with the completion of clinical trials Hypersensitivity to investigational medicinal products History of alcohol, substance abuse or dependence (except nicotine dependence) within the last 2 years Concurrent malignancies or invasive cancers diagnosed within the past 5 years except for non-metastatic basal cell carcinoma or squamous cell carcinoma of skin, in situ carcinoma of the uterine cervix or non-metastatic prostate cancer Renal impairment (creatinine clearance (CLcr) <30 mL / min) Severe liver dysfunction (ALT or AST> 2 times the upper limit of normal) A patient taking other drugs other than donepezil to treat Alzheimer's disease or other cognitive impairment A patient taking other drugs other than anticholinergic drugs, cholinergic drugs (local usages are allowable, such as pilocarpine eye drops), antidepressants (tricyclic antidepressant, MAO inhibitor) antipsychotics, donepezil to treat Alzheimer's disease Women at childbearing age who do not consent using medicinally acceptable contraception (such as surgical sterilization, intrauterine contraceptive device, condom or diaphragm, an injectable or inserted contraceptive) during the study Pregnancy or breast feeding A patient who participated in other clinical trials within 4 weeks prior to this study 35 kg weight or below A patient who had experienced this study drug A patient who had participated in a clinical trial for Alzheimer dementia vaccine within last 6 months Any other patients who are considered to be ineligible for this study by an investigator

Ages Eligible for Study
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Minimum Age: 55 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 |
| --- | --- |
| Placebo Comparator: Control group<br>Normal saline 0.9% | Drug: Normal Saline 0.9%<br>* Normal saline 0.9% is subcutaneously administered once weekly schedule for 4 weeks (4 times) followed by every two weeks until week 24 (10 times). A total number of administration is 14 times.<br>* Other names: NS 0.9%;|
| Experimental: Study group 1<br>GV1001 0.56 mg | Drug: GV1001 0.56 mg<br>* GV1001 0.56 mg is subcutaneously administered once weekly schedule for 4 weeks (4 times) followed by every two weeks until week 24 (10 times). A total number of administration is 14 times.<br>* Other names: Tertomotide;|
| Experimental: Study group 2<br>GV1001 1.12 mg | Drug: GV1001 1.12 mg<br>* GV1001 1.12 mg is subcutaneously administered once weekly schedule for 4 weeks (4 times) followed by every two weeks until week 24 (10 times). A total number of administration is 14 times.<br>* Other names: Tertomotide;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| SIB (Severe Impairment Battery) | Change in SIB compared to the baseline and week 24 | week 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| K-MMSE (Korean-Mini-Mental State Examination) | Change in K-MMSE compared to the baseline and week 24 | week 24 | 
| CDR-SOB (Clinical Dementia Rating-Sum of Box) | Change in CDR-SOB compared to the baseline and week 24 | week 24 | 
| NPI (Neuropsychiatric Inventory) | Change in NPI compared to the baseline and week 24 | week 24 | 
| GDS (Global Deterioration Scale) | Change in GDS compared to the baseline and week 24 | week 24 | 
| ADCS-ADL-severe (Alzheimer's Disease Cooperative Study-Activities of Daily Living scale-severe) | Change in ADCS-ADL-severe compared to the baseline and week 24 | week 24 | 
| CIBIC-plus (Clinician Interview-Based Impression of Change-Plus) | Change in CIBIC-plus compared to the baseline and week 24 | week 24 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Alzheimer Disease, GV1001