Evaluation of the Safety and Efficacy of Subcutaneous Tertomotide (GV1001) in Mild to Moderate Alzheimer's Disease: A Randomized, Double-Blind, Placebo-Controlled Study

Trial ID: 2024-511610-20-00
Protocol: GV1001-AD-CL2-007
Sponsor: Gemvax & Kael Co. Ltd.

Trial statistics

science

test molecules

location_city

research sites

public

countries

medical_information

disease

person_search

investigators

handshake

vendors

Diseases & Conditions

Dementia Alzheimer's type

Objectives

The primary objective of this study is to evaluate the **efficacy** of GV1001, administered at doses of 0.56 mg and 1.12 mg, compared to placebo, on cognition in participants with mild to moderate **Alzheimer's Disease** (AD). This is measured using the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-cog11). Additionally, the study aims to assess the safety of GV1001 in this patient population. The clinical relevance of this objective lies in the potential to improve cognitive function in individuals with AD, a condition characterized by progressive cognitive decline.

Secondary objectives include evaluating the efficacy of GV1001 relative to placebo on both cognition and function in participants with mild to moderate AD. This is assessed through various measures: ADAS-cog11, Amsterdam Instrumental Activities of Daily Living Questionnaire (A-IADL-Q), Neuropsychiatric Inventory (NPI), Mini-Mental State Examination (MMSE), Clinical Dementia Rating-Sum of Boxes (CDR-SB), Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change/Clinician's Interview-Based Impression of Change Plus (ADCS-CGIC/CIBIC Plus), and Quality of Life in Alzheimer's Disease (QoL-AD). These assessments provide a comprehensive evaluation of the impact of GV1001 on both cognitive and functional aspects of AD, which are critical for understanding the overall therapeutic potential of the treatment.

Participants

The clinical trial involves a total of **77 participants** diagnosed with **Alzheimer's Disease**. The study population comprises both male and female subjects, aged between 55 and 85 years. Participants were selected based on a diagnosis of probable Alzheimer's Disease, confirmed by criteria such as the NINCDS-ADRDA and supported by findings from MRI or Aβ PET scans. The trial includes individuals with mild to moderate dementia, as indicated by a Mini-Mental State Examination (MMSE) score ranging from 13 to 24. Participants are required to have a caregiver who can accompany them to study visits and assist with compliance to study procedures. The trial population is characterized by a stable health status, with any approved medication for Alzheimer's Disease maintained at a stable dose for at least 12 weeks prior to screening. Additionally, participants may be using over-the-counter supplements for cognition, provided they do not exceed recommended doses. The study includes a vulnerable population, necessitating careful monitoring and support throughout the trial duration.

Plans and Procedures

The clinical trial is a **randomized**, **double-blind**, **placebo-controlled** study designed to evaluate the safety and efficacy of GV1001, administered subcutaneously, for the treatment of mild to moderate **Alzheimer's Disease**. The trial follows a parallel design and is conducted over a period of 52 weeks. Participants are randomly assigned to receive either GV1001 at doses of 0.56 mg or 1.12 mg, or a placebo, with the primary objective of assessing changes in cognitive function as measured by the ADAS-Cog11 score. The trial also aims to monitor safety through adverse events, laboratory tests, ECG findings, and vital signs.

The study involves several key visits, beginning with an inclusion (screening) visit where eligibility is confirmed based on criteria such as age, diagnosis of probable Alzheimer's Disease, and cognitive function scores. Participants must provide written informed consent, and women of childbearing potential must have a negative pregnancy test. Following randomization, participants attend regular follow-up visits at Weeks 12, 26, 38, and 52 to assess both primary and secondary endpoints, including changes in various cognitive and functional scores. The end-of-study visit occurs at Week 52, marking the conclusion of the participant's involvement in the trial.

Participant involvement is expected to last approximately 52 weeks, with conditions for early termination including significant adverse events or withdrawal of consent. The trial is structured to ensure rigorous monitoring and assessment of both efficacy and safety, with the ultimate goal of advancing treatment options for individuals with mild to moderate Alzheimer's Disease.

Treatment

The clinical trial involves the administration of **GV1001**, an experimental medication containing the active substance **tertomotide**. This medication is provided in the form of an **injection** and is intended for **subcutaneous use**. The trial includes two dosage regimens of GV1001: 1.12 mg and 0.56 mg. The maximum daily dose for the 1.12 mg regimen is 1.12 mg, with a total maximum dose of 30.24 mg over a treatment period of 50 weeks. For the 0.56 mg regimen, the maximum daily dose is 0.56 mg, with a total maximum dose of 15.12 mg over the same treatment period. The administration schedule is designed to ensure consistent dosing throughout the trial duration. Participant compliance with the dosing schedule will be monitored to ensure adherence to the protocol.

In addition to the experimental treatment, the study employs a **placebo** control, which is a solution for injection with no active substance. The placebo is used to maintain the double-blind nature of the trial, ensuring that neither the participants nor the investigators are aware of the treatment assignments. The placebo is administered in the same manner as the experimental medication, via subcutaneous injection, to maintain consistency in the administration process. This approach allows for a rigorous evaluation of the efficacy and safety of GV1001 in comparison to the placebo in participants with mild to moderate Alzheimer's disease.

Efficacy

The efficacy of GV1001 in the treatment of mild to moderate **Alzheimer's Disease** will be assessed through a series of primary and secondary endpoints. The primary efficacy endpoint is the change from baseline in the ADAS-Cog11 score at Week 52. This endpoint will evaluate the cognitive function of participants, providing a quantitative measure of the drug's impact on cognitive decline associated with Alzheimer's Disease.

Secondary efficacy endpoints include several measures to capture a broader spectrum of clinical outcomes. These include clinical worsening, defined as a change of ≥4 points from baseline in the ADAS-Cog11 score at Weeks 12, 26, 38, and 52. Additional secondary endpoints involve changes from baseline in the A-IADL-Q, NPI, MMSE, CDR-SB, and ADCS-CGIC/CIBIC-Plus scores at specified intervals (Weeks 12, 26, 38, and 52), as well as changes in the QoL-AD score at Weeks 26 and 52. These assessments will provide insights into the functional, behavioral, and quality of life aspects of the participants.

The efficacy parameters will be measured using validated scales and instruments at predetermined timepoints throughout the 52-week study period. Data collection will occur at baseline and at subsequent intervals, allowing for a comprehensive analysis of the treatment's impact over time. The analysis will focus on comparing the changes in these scores between the treatment and placebo groups to determine the efficacy of GV1001 in this patient population.

Inclusion and Exclusion Criteria

check_circle

Inclusion Criteria

Male or female participants 55 to 85 years of age (both inclusive) at the time of signing the informed consent.
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
Mild or moderate dementia as evidenced by MMSE score ≥13 to ≤24 at screening (Visit 1).
Not applicable.
Not applicable.
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).
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.
Able to visit the study center and undergo cognitive, functional, and other tests specified in the protocol
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
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.
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.
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.
Written informed consent provided by participant (or legal representative) and caregiver prior to any study-specific procedures.

cancel

Exclusion Criteria

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)
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
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.
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.
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
Known allergies, hypersensitivity, or intolerance to GV1001 or similar products or excipients
History of alcohol, substance abuse or dependence as per DSM-V criteria (except nicotine dependence) within the last 2 years.
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.
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.
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.
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.
Previous treatment with GV1001.
Received an investigational product for AD within the last 6 months.
Participated in another clinical study within 4 weeks prior to this study.
Treated with amyloid targeting drugs or participated in a clinical study with amyloid targeting drugs
Renal impairment (creatinine clearance [CrCL] <30 mL/min)
Severe liver dysfunction (alanine aminotransferase [ALT] or aspartate aminotransferase [AST] >2 times the upper limit of normal [ULN])
Body weight ≤35 kg
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)
Any other reason that in the opinion of the Investigator would make the participant ineligible to participate or to complete this study

Trial Status by Country

Country	Status	Start of Recruitment	Planned Patients
Finland	Not Recruiting	12 Dec 2022	2
France	Not Recruiting	12 Dec 2022	5
Italy	Not Recruiting	12 Dec 2022	1
The Netherlands	Not Recruiting	12 Dec 2022	—
Poland	Not Recruiting	12 Dec 2022	21
Portugal	Not Recruiting	12 Dec 2022	15
Spain	Not Recruiting	12 Dec 2022	54
Netherlands	—	—	5