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The objective of this study is to evaluate the safety and efficacy of GV1001 administered subcutaneously in patients with moderate to severe Alzheimer's disease (AD).
Studies using in vivo and in vitro Alzheimer's Disease (AD) models have shown that GV1001 inhibits neurotoxicity, apoptosis, and the production of reactive oxygen species induced by amyloid beta (Aβ) 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 was shown to improve cognitive function and memory, as well as significantly reduce the amount of Aβ and tau proteins. The multifunctional effect of GV1001 makes it a promising therapeutic option for the treatment for AD. In a completed Phase 2 study (NCT03184467) conducted in Korea, GV1001 showed significant improvement in change from baseline of Severe Impairment Battery score at Week 24 and demonstrated a clinically acceptable safety profile in patients with moderate to severe AD.
This is a multi-center, randomized, double-blinded, placebo-controlled, parallel design, prospective phase 3 study in participants with moderate to severe AD. The study consists of 24 weeks of Double-blind phase and 25 weeks of open-label phase.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| GV1001 Placebo | Placebo Comparator | GV1001 placebo (0.9% saline) subcutaneous injection will be administered once a week for 4 weeks and then administered every 2 weeks for 20 weeks in a double-blind phase. During the open-label extension phase, patients assigned to the GV1001 Placebo arm in the double-blind phase will receive a placebo in the first week, followed by 1.12 mg of GV1001 weekly for 4 weeks and then every 2 weeks until EOT (End of Treatment). |
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| GV1001 1.12 mg | Experimental | GV1001 1.12 mg subcutaneous injection will be administered once a week for 4 weeks and then administered every 2 weeks for 20 weeks in a double blind phase. During the open-label extension phase, patients will alternate between 1.12 mg of GV1001 and placebo weekly for the first 5 weeks to maintain double blindness, and then 1.12mg of GV1001 every 2 weeks until EOT. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| GV1001 Placebo | Drug | 0.9% normal saline |
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| Measure | Description | Time Frame |
|---|---|---|
| Change from baseline in SIB(Severe Impairment Battery) score after GV1001 administration for 24 weeks | SIB includes 51 questions to assess cognition in an individual. SIB consists of nine symptom domains such as attention, language, orientation, memory, praxis, visuospatial perception, construction, social skills and orientating head to name. The possible total scores range from 0 to 100 with a higher score indicating greater cognitive function. | Baseline, Week 26 |
| CIBIC-plus (Clinician Interview-Based Impression of Change-Plus) score after GV1001 administration for 24 weeks | CIBIC-plus consists of 4 items: "Overall," "Mental and Cognitive Function," "Behavior," and "Daily Function." CIBIS, a 7-point severity assessment, is administered at baseline. CIBIC-plus is implemented at follow-up visits to evaluate the degree of change in overall functional status in 7 levels by referring to the CIBIS results evaluated at baseline. The overall clinical condition of the dementia patient is assessed based on information obtained from semi-structured interviews of patients and caregivers. The rater is independent, has clinical experience, and will evaluate the subjects after completing the training required for this study. | Baseline, Week 26 |
| Measure | Description | Time Frame |
|---|---|---|
| Change from baseline in SIB(Severe Impairment Battery) score | SIB includes 51 questions to assess cognition in an individual. SIB consists of nine symptom domains such as attention, language, orientation, memory, praxis, visuospatial perception, construction, social skills and orientating head to name. The possible total scores range from 0 to 100 with a higher score indicating greater cognitive function. |
| Measure | Description | Time Frame |
|---|---|---|
| Exploratory Assessment | [Long-term administration] Change in Severe Impairment Battery (SIB) score at 28, 36, and 48 weeks after administration of the investigational drug compared to baseline /Unit of Measure: Severe Impairment Battery (SIB) scale (values range from 0 to 100; higher scores indicate a better outcome / less cognitive impairment) | 28, 36, and 48 weeks after administration of IP |
Inclusion Criteria:
Exclusion Criteria:
Subjects who have other causes of dementia as listed below according to CT/MRI test and neurologic examination within 12 months of screening or at the time of screening.
Subjects who have abnormal test results which are considered to contribute to the severity of their dementia or be the cause of dementia in the vitamin B12, folic acid, syphilis serology, and the thyroid stimulating hormone (TSH) tests
Subjects who have a history of significant psychiatric illness such as schizophrenia or bipolar affective disorders which may interfere with the participation of this clinical trial according to the investigator's judgment or who are suffering from depression
Subjects with a history of known or suspected seizures including febrile seizure, recent loss of consciousness which is not explained or history of significant head trauma accompanied by loss of consciousness
Subjects in any medical condition that may interfere with the evaluation and progression of the clinical trial according to the investigator's judgment (acute or unstable cardiovascular disease, uncontrolled hypertension (>160/100 mmHg) at Visit 1 and Visit 2, insulin-dependent or uncontrolled diabetes at Visit 1 (HbA1c> 8% on screening test), etc.).
Subjects who are hypersensitive to the components of the investigational product.
Subjects with a history of alcohol and drug abuse or dependence (except nicotine dependence) within the last 2 years.
Subjects with a history of cancer within the past 5 years (however, non-metastatic skin basal cell carcinoma and/or skin squamous cell carcinoma, carcinoma in suit of uterine cervix or non-progressive prostate cancer may be acceptable and If cancer is considered to have been treated at the judgement of the investigator, if subjects are not taking anticancer or radiation therapy and are considered that treatment is not required for the next 5 years at the discretion of the investigator, enrollment is possible)
Subjects with renal dysfunction (Creatinine Clearance (Clcr) < 30 mL/min)
Subjects with serious hepatic dysfunction (Alanine aminotransferase or Aspartate aminotransferase ≥ 2.0 normal upper limit)
Subjects currently receiving or expected to receive medications prohibited in this clinical trial during the trial period
• Donepezil, memantine, or other medications for the treatment of Alzheimer's disease (acetylcholinesterase inhibitors (rivastigmine, galantamine), anti-amyloid antibodies (lecanemab, donanemab), etc.) or other medications for the treatment of cognitive impairment.
Subjects with previous administration of all clinical trial vaccines for Alzheimer's disease
Among subjects who consented to lumbar puncture (LP) for cerebrospinal fluid (CSF) collection, patients meeting the following criteria
- Patients with contraindications for lumbar puncture (e.g., platelet count <100,000/μL, lumbar deformity, etc.) (However, even if a subject has contraindications for lumbar puncture, they may still participate in this clinical trial.)
Female subjects with childbearing potential who do not agree to contraception using a medically accepted method (complete celibacy; hormonal contraceptives: Levonorgestrel, Intrauterine system of Mirena, and Medroxyprogesterone; and surgical sterilizations: vasectomy, double tubectomy, double tubal ligation) during the clinical trial period and until 90 days after clinical trial end (stop).
Pregnant or lactating women
Subjects who participated in another clinical trial within 4 weeks before participation in this clinical trial
Subjects in less than 12 months after the administration of the Investigational product for this clinical trial
Subjects who participated in any clinical trial for Alzheimer type dementia treatment within 6 months at screening
Subjects who are judged by the investigator to be ineligible for participation in this clinical trial
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Kyounghee Seo | Contact | +82 31 353 6681 | khseo@sspharm.co.kr | |
| Soyoung Park | Contact | +82 70 4840 9243 | soyoung@sspharm.co.kr |
| Name | Affiliation | Role |
|---|---|---|
| Kyounghee Seo | Samsung Pharmaceutical Co., Ltd. | Study Director |
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| ID | Term |
|---|---|
| D000544 | Alzheimer Disease |
| ID | Term |
|---|---|
| D003704 | Dementia |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
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| ID | Term |
|---|---|
| D000077330 | Saline Solution |
| ID | Term |
|---|---|
| D000077324 | Crystalloid Solutions |
| D007552 | Isotonic Solutions |
| D012996 | Solutions |
| D004364 | Pharmaceutical Preparations |
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| GV1001 1.12mg | Drug | Lyophilized peptide from hTERT |
|
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| Baseline, Week 6, and Week 14 |
| CIBIC-plus (Clinician Interview-Based Impression of Change-Plus) score after GV1001 administration | CIBIC-plus consists of 4 items: "Overall," "Mental and Cognitive Function," "Behavior," and "Daily Function." CIBIS, a 7-point severity assessment, is administered at baseline. And CIBIC-plus is implemented at follow-up visits to evaluate the degree of change in overall functional status in 7 levels by referring to the CIBIS results evaluated at baseline. The overall clinical condition of the dementia patient is assessed based on information obtained from semi-structured interviews of patients and caregivers. The rater is independent, has clinical experience, and will evaluate the subjects after completing the training required for this study. | Baseline, Week 6, and Week 14 |
| Change from baseline in K-MMSE(Korea Mini-Mental State Examination) score after GV1001 administration | K-MMSE assesses an individual's cognitive function by asking questions about time orientation, spatial orientation, memory registration, attention and calculation, memory recall, language, and space-time configuration. It creates the possible total score from 0 to 30, with a lower total score indicating greater severity in cognitive impairment. | Baseline, Week 6 week, Week 14, and Week 26 |
| Change from baseline in ADCS-ADL-severe(Alzheimer's Disease Cooperative Study-Activities of Daily Living scale-severe) score after GV1001 administration | ADCS-ADL-severe consists of 19 items that can access the competence of individuals with AD in activities of daily living. The maximum possible total score is 54, with a higher score indicating lesser severity in AD. | Baseline, Week 6 week, Week 14, and Week 26 |
| Change from baseline in CDR-SOB(Clinical Dementia Rating Scale Sum of Boxes) score after GV1001 administration | CDR-SOB evaluates cognitive and functional performance in six domains related to AD including memory, orientation, judgment and problem solving, community affairs, home and hobbies, and personal care. Each domain is rated from 0 to 5 points (0, 0.5, 1, 2, 3, 4, and 5) with a lower total score indicating severely impaired cognitive function. | Baseline, Week 6 week, Week 14, and Week 26 |
| Change from baseline in GDS(Global Deterioration Scale) score after GV1001 administration | GDS provides the stages for the severity of cognitive function of the individual with AD. It is brown down into seven stages (stage1=no cognitive decline and 7=very severe cognitive decline). | Baseline, Week 6 week, Week 14, and Week 26 |
| Change from baseline in NPI-Q(Neuropsychiatric Inventory Questionnaire) score after GV1001 administration | NPI-Q consists of questions to evaluate degrees of behavioral disturbance in 12 domains. It includes delusions, hallucinations, agitation/aggression, depression/dysphoria, anxiety, elation/euphoria, apathy/indifference, disinhibition, irritability/lability, motor disturbance, nighttime behaviors, and appetite/eating. The severity scale has scores ranging from 1 to 3 points (1=mild and 3=severe) and the scale for assessing caregiver distress has scores ranging from 0 to 5 points (0=no distress and 5=extreme distress). The higher sum of the NPI-Q severity score represents greater severity of the individual's symptoms, and the higher sum of the NPI-Q distress score indicates greater severity of caregiver's distress associated with the symptoms. | Baseline, Week 6 week, Week 14, and Week 26 |
| Exploratory Assessment | [Long-term administration] Change in Clinical Dementia Rating-Sum of Boxes (CDR-SOB) score at 28, 36, and 48 weeks after administration of the investigational drug compared to baseline / Unit of Measure: Clinical Dementia Rating-Sum of Boxes (CDR-SOB) scale (total scores range from 0 to 18; higher scores indicate a worse outcome / greater cognitive and functional impairment) | 28, 36, and 48 weeks after administration of IP |
| Exploratory Assessment | [Long-term administration] Change in Korean Mini-Mental State Examination (K-MMSE) score at 28, 36, and 48 weeks after administration of the investigational drug compared to baseline / Unit of Measure: Korean Mini-Mental State Examination (K-MMSE) scale (values range from 0 to 30; higher scores indicate a better outcome / better cognitive function) | 28, 36, and 48 weeks after administration of IP |
| Exploratory Assessment | [Long-term administration] Change in Alzheimer's Disease Cooperative Study - Activities of Daily Living - Severe (ADCS-ADL-severe) score at 28, 36, and 48 weeks after administration of the investigational drug compared to baseline / Unit of Measure: Alzheimer's Disease Cooperative Study - Activities of Daily Living - Severe (ADCS-ADL-severe) scale (values range from 0 to 18; higher scores indicate a better outcome / better functional ability) | 28, 36, and 48 weeks after administration of IP |
| Exploratory Assessment | [Long-term administration] Change in Global Deterioration Scale (GDS) score at 28, 36, and 48 weeks after administration of the investigational drug compared to baseline / Unit of Measure: Global Deterioration Scale (GDS) (stages range from 1 to 7; higher scores indicate a worse outcome / greater cognitive decline) | 28, 36, and 48 weeks after administration of IP |
| Exploratory Assessment | [Long-term administration] Change in Neuropsychiatric Inventory Questionnaire (NPI-Q) score at 28, 36, and 48 weeks after administration of the investigational drug compared to baseline / Unit of Measure: Neuropsychiatric Inventory Questionnaire (NPI-Q) scale (total severity scores range from 0 to 36; higher scores indicate a worse outcome / more severe neuropsychiatric symptoms) | 28, 36, and 48 weeks after administration of IP |
| Exploratory Assessment | [Long-term administration] Change in Clinician's Interview-Based Impression of Change Plus Caregiver Input (CIBIC-plus) score at 28, 36, and 48 weeks after administration of the investigational drug compared to baseline / Unit of Measure: Clinician's Interview-Based Impression of Change Plus Caregiver Input (CIBIC-plus) scale (values range from 1 to 7; higher scores indicate a worse outcome / clinical worsening) | 28, 36, and 48 weeks after administration of IP |
| Exploratory Assessment | [Biomarker Test] - Plasma: Change from baseline (Visit 1) to Week 24 and Week 48 of Investigational Product (IP) administration in Amyloid Beta Peptide 1-42 (Aβ1-42), Aβ1-40, total Tau (t-Tau), phosphorylated Tau (p-Tau), p-Tau 181, p-Tau 217, p-Tau 231, Neurofilament Light Chain (NfL), Glial Fibrillary Acidic Protein (GFAP) change / Unit of Measure: pg/mL | Change from baseline to Week 24 and Week 48 of IP administration |
| Exploratory Assessment | [Biomarker Test] - Cerebrospinal Fluid (CSF): Change from baseline (Visit 2) to Week 24 and Week 48 of Investigational Product (IP) administration in Aβ1-42, Aβ1-40, t-Tau, p-Tau, p-Tau 181, p-Tau 217, p-Tau 231, NfL, GFAP, Brain-Derived Neurotrophic Factor (BDNF), YKL-40, Neurogranin, Neuron-Specific Enolase (NSE), S100B change / Unit of Measure: pg/mL or ng/mL | Change from baseline to Week 24 and and Week 48 of IP administration |
| D024801 |
| Tauopathies |
| D019636 | Neurodegenerative Diseases |
| D019965 | Neurocognitive Disorders |
| D001523 | Mental Disorders |