GV1001 Subcutaneous for the Treatment of Moderate to Severe Alzheimer's Disease(AD)

A Multi-Center, Randomized, Double-Blind, Placebo-Controlled, Parallel Design, Prospective, Phase III Clinical Trial to Evaluate the Efficacy and Safety of Subcutaneous Administration of GV1001 1.12 mg/Day in Patients With Moderate to Severe Alzheimer Disease

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.

Inclusion Criteria:

1. Subjects aged ≥ 55 to ≤ 85 years
2. Subjects who satisfy diagnostic criteria for dementia in DSM-IV (Diagnostic and Statistical Manual of Mental Disorders Fourth edition)
3. Subjects who are clinically diagnosed with probable Alzheimer's disease as defined in the NINCDS-ADRDA (National Institute of Neurological and Communicative Diseases and Stroke/Alzheimer's Disease and Related Disorders Association) criteria
4. Subjects with a K-MMSE (Korea Mini-Mental State Examination) score ≤ 19 at the screening visit
5. Subjects with GDS (Global Deterioration Scale) grade 5 to 6
6. Subjects who have no other diseases to cause dementia other than AD as a result of MRI or CT scan within 12 months from the screening visit
7. Subjects who are taking donepezil alone or donepezil and memantine in combination at a stable dose without a dose change over 3 months before screening
8. Subjects who are not illiterate
9. Subjects who can walk with or without assist device to visit hospitals or clinics to undergo cognitive tests and other tests
10. Subjects with caregiver who can accompany all visits with the subjects as scheduled for this trial, supervise subject's compliance for the tests and examination process and provide information about the subject's indications, and who give written consent
11. Subjects and/or legal representative who voluntarily agreed in written to participate in the clinical trial

Exclusion Criteria:

1. 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 with possible, probable or definite vascular dementia according to NINDS-AIREN (National Institute of Neurological Disorders and Stroke and the Association Internationale pour la Recherche et l'Enseignement en Neurosciences) criteria
   • Subjects with other central nervous system diseases that can cause the impairment of cognitive function (cerebrovascular disease including cerebrovascular dementia, Parkinsonism, Huntington's disease, subdural hematoma, normal pressure hydrocephalus, brain tumor, Creutzfeldt-Jakob disease, etc.)
   • Subjects with neuropathy such as delusion, delirium, epilepsy, etc.

2. 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

3. 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

4. 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

5. 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.).

6. Subjects who are hypersensitive to the components of the investigational product.

7. Subjects with a history of alcohol and drug abuse or dependence (except nicotine dependence) within the last 2 years.

8. 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)

9. Subjects with renal dysfunction (Creatinine Clearance (Clcr) < 30 mL/min)

10. Subjects with serious hepatic dysfunction (Alanine aminotransferase or Aspartate aminotransferase ≥ 2.0 normal upper limit)

11. 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.

12. Subjects with previous administration of all clinical trial vaccines for Alzheimer's disease

13. 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.)

14. 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).

15. Pregnant or lactating women

16. Subjects who participated in another clinical trial within 4 weeks before participation in this clinical trial

17. Subjects in less than 12 months after the administration of the Investigational product for this clinical trial

18. Subjects who participated in any clinical trial for Alzheimer type dementia treatment within 6 months at screening

19. Subjects who are judged by the investigator to be ineligible for participation in this clinical trial