A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel Design, Prospective, 52-Week, Phase 2 Clinical Study to Evaluate the Safety and Efficacy of GV1001 Administered Subcutaneously for the Treatment of Mild to Moderate Alzheimer’s Disease

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Gemvax & Kael Co. Ltd.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nervous System Diseases [C10]

Trial duration

8 Nov 2022 → 17 Apr 2025

Decision date (initial)

2024-05-06

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

GemVax & KAEL Co., Ltd.

External identifiers

EU CT number

2024-511610-20-00

EudraCT number

2021-004809-40

ClinicalTrials.gov

NCT05189210

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Therapy, Others, Efficacy

1. To evaluate the efficacy of GV1001 (0.56 mg and 1.12 mg) relative to placebo on cognition in participants with mild to moderate AD, as measured by ADAS-cog11
2. To evaluate the safety of GV1001 in participants with mild to moderate AD

Secondary objectives 1

1. To evaluate the efficacy of GV1001 (0.56 mg and 1.12 mg) relative to placebo on cognition and function in participants with mild to moderate AD, as measured by: •ADAS-cog11 •A-IADL-Q •NPI •MMSE •CDR-SB •ADCS-CGIC/CIBIC Plus •QoL-AD

Conditions and MedDRA coding

Alzheimer's Disease

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 13

1. 1. Male or female participants 55 to 85 years of age (both inclusive) at the time of signing the informed consent.
2. 2. Diagnosis of probable AD based on NINCDS-ADRDA criteria (a and b) as determined by a neurologist, geriatrician, psychiatrist, or clinician approved by the Sponsor or designee. a. Presence of an early and significant episodic memory impairment that includes the following features: i. Gradual and progressive change in memory function reported by patients or informants over >6 months. ii. Objective evidence of significantly impaired episodic memory on testing: this generally consists of recall deficit that does not improve significantly or does not normalize with cueing or recognition testing and after effective encoding of information has been previously controlled. iii. The episodic memory impairment can be isolated or associated with other cognitive changes at the onset of AD or as AD advances. b. One or more findings for probable AD by either MRI, Aβ PET scan, historical CSF results, or a historical genetic test in the 2 years before screening, or an MRI or Aβ PET scan at screening. The MRI must have findings consistent with AD and without any other disease that may cause dementia. The Aβ PET scan and historical CSF results must be consistent with the presence of amyloid pathology
3. 3. Mild or moderate dementia as evidenced by MMSE score ≥13 to ≤24 at screening (Visit 1).
4. 4. Not applicable.
5. 5. Not applicable.
6. 6. If receiving an approved medication for AD (except amyloid targeting drugs), must be on the medication with a stable dose for at least 12 weeks before the screening visit (dosing should remain stable throughout the study).
7. 7. If receiving an OTC supplement for cognition (eg, gingko biloba, omega-3 polyunsaturated fatty acid, vitamin E, curcumin), must not be exceeding the recommended dose for at least 12 weeks prior to screening visit.
8. 8. Able to visit the study center and undergo cognitive, functional, and other tests specified in the protocol
9. 9. Has a caregiver who: • Agrees to accompany the participant to all study visits and able to supervise the participant's compliance with the study procedures and provide detailed information about the participant. • Either lives with the participant or sees the participant on average for ≥1 hour/day ≥3 days/week, or in the Investigator's opinion, the extent of contact is sufficient to provide meaningful assessment of changes in participant behavior and function over time and provide information on safety and tolerability. • Is able to read, understand, and speak the designated language at the study center. • Caregiver must be cognitively able to fulfill the requirements of the study
10. 10. A male participant must agree to use a highly effective contraception method during the treatment period and for at least 3 months after the last dose of study treatment and refrain from donating sperm during this period.
11. 11. A female participant is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies: • Not a woman of childbearing potential (WOCBP). OR • A WOCBP who agrees to use a highly effective contraception method during the treatment period and for at least 3 months after the last dose of study treatment.
12. 12. A WOCBP must have a negative serum pregnancy test at screening (Visit 1) and a negative urine pregnancy test at Visit 2 before randomization, and must use medically accepted means of contraception throughout the study.
13. 13. Written informed consent provided by participant (or legal representative) and caregiver prior to any study-specific procedures.

Exclusion criteria 20

1. 1. Any other cause of dementia shown by MRI/CT findings within 2 years of screening (or at screening) and neurological examination at screening and Day 1. • Possible, probable, or definite vascular dementia according to the National Institute of Neurological Disorders and Stroke and Association Internationale pour la Recherché et l'Enseignement en Neurosciences (NINDS-AIREN) criteria. • Evidence of significant abnormality that would suggest another potential etiology for dementia (eg, evidence of cerebral contusion, encephalomalacia, aneurysm, vascular malformation, >5 microhemorrhages, macrohemorrhage, single infarct >1 cm3). • Other central nervous system diseases that may cause cognitive impairment (eg, cerebrovascular disease including cerebrovascular dementia, Parkinsonism, Huntington's disease, subdural hematoma, normal pressure hydrocephalus, brain tumor, Creutzfeldt-Jakob disease)
2. 2. Concurrent or history of schizophrenia or bipolar disorder; OR any other clinically significant psychiatric conditions that in the Investigator's opinion prevents the participant from participating, or is likely to confound interpretation of drug effect or affect cognitive assessments or participant safety; OR the presence or history of suicidal attempts or suicidal ideation evidenced by endorsing Items 4 or 5 of the C-SSRS at screening or Day 1, endorsing any suicidal behavior item on the C-SSRS Since Last Visit form on Day 1, or any suicide attempt within 2 years prior to screening
3. 3. Vitamin B12, folic acid, syphilis serology, and thyroid stimulating hormone (TSH) results that are thought to contribute to the severity of dementia or cause dementia. Participants may be enrolled if in the Investigator's medical judgment, the abnormal laboratory values are not the cause of the cognitive symptoms.
4. 4. History of known or suspected seizures including febrile seizures (excluding self-limited childhood febrile seizures), a history of significant head trauma with loss of consciousness or recent unconsciousness that is not explained.
5. 5. 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 the clinical study
6. 6. Known allergies, hypersensitivity, or intolerance to GV1001 or similar products or excipients
7. 7. History of alcohol, substance abuse or dependence as per DSM-V criteria (except nicotine dependence) within the last 2 years.
8. 8. Concurrent malignancies or invasive cancers diagnosed within the past 5 years except for adequately treated non-metastatic basal cell carcinoma or squamous cell carcinoma of skin, in situ carcinoma of the uterine cervix or non-metastatic prostate cancer.
9. 9. Sexually-active WOCBP or man capable of fathering a child who do not consent to using medicinally acceptable contraception (such as surgical sterilization, intrauterine contraceptive device, condom or diaphragm, an injectable or inserted contraceptive) during the study and for 3 months after the last dose of study treatment.
10. 10. Pregnant, breast feeding, or planning a pregnancy or fathering a child while enrolled in the study or for 3 months after the last dose of study treatment.
11. 11. Use of anxiolytics, narcotics, or sleep aids in a manner that would interfere with cognitive testing, in the opinion of the Investigator. Atypical antipsychotics may be used at the discretion of the Investigator. Tricyclic antidepressants and monoamine oxidase (MAO) inhibitors are prohibited.
12. 12. Previous treatment with GV1001.
13. 13. Received an investigational product for AD within the last 6 months.
14. 14. Participated in another clinical study within 4 weeks prior to this study.
15. 15. Treated with amyloid targeting drugs or participated in a clinical study with amyloid targeting drugs
16. 16. Renal impairment (creatinine clearance [CrCL] <30 mL/min)
17. 17. Severe liver dysfunction (alanine aminotransferase [ALT] or aspartate aminotransferase [AST] >2 times the upper limit of normal [ULN])
18. 18. Body weight ≤35 kg
19. 19. Resides in a moderate to high dependency continuous care facility (residence in low grade assisted living facility where there is sufficient autonomy to permit valid evaluation of activities of daily living is allowed)
20. 20. Any other reason that in the opinion of the Investigator would make the participant ineligible to participate or to complete this study

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. 1. Change from baseline in ADAS-Cog11 score at Week 52
2. 2. Adverse events (AEs), laboratory test results (hematology, serum chemistry, and urinalysis), ECG findings, and vital signs measurements (pulse rate, blood pressure, respiratory rate, body temperature). Suicidal ideation and behavior will be assessed using the Columbia-Suicide Severity Rating Scale (C-SSRS)

Secondary endpoints 7

1. Secondary efficacy endpoints: • Clinical worsening, defined as ≥4 points change from baseline in the ADAS-cog11 score at Week 12, Week 26, Week 38, and Week 52
2. • Change from baseline in A-IADL-Q score at Week 12, Week 26, Week 38 and Week 52
3. • Change from baseline in NPI score at Week 12, Week 26, Week 38, and Week 52
4. • Change from baseline in MMSE score at Week 12, Week 26, Week 38, and Week 52
5. • Change from baseline in CDR-SB score at Week 12, Week 26, Week 38, and Week 52
6. • Change from baseline in ADCS-CGIC/CIBIC-Plus score at Week 12, Week 26, Week 38, and Week 52
7. • Change from baseline in QoL-AD score at Week 26 and Week 52

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Gemvax & Kael Co. Ltd.

Sponsor organisation

Gemvax & Kael Co. Ltd.

Address

Techno 11 Ro 58

City

Yuseong-Gu

Postcode

34036

Country

Korea, Republic of

Scientific contact point

Organisation

Gemvax & Kael Co. Ltd.

Contact name

Director of Clinical Operations

Public contact point

Organisation

Gemvax & Kael Co. Ltd.

Contact name

Director of Clinical Operations

Third parties 11

Locations

7 EU/EEA countries · 25 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Summary of results Art. 37(4) CTR

Layperson summary Annex V

Documents 72 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

4 submissions — initial application plus substantial / non-substantial modifications