Condition or disease | Intervention/treatment | Phase |
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Moderate Alzheimer's Disease | Drug: GV1001 Drug: Normal saline | Phase 2 |
This is a multicenter, randomized, double-blind, placebo-controlled, dose finding, parallel-group Phase IIa study in participants with moderate AD. The study population will be comprised of male and female participants between 55 and 85 years of age, inclusive, with a diagnosis of probable AD based on National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association (NINCDS ADRDA) criteria. Participants must also meet Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-V) criteria for dementia and have an Mini-Mental State Examination (MMSE) score ≥10 to <20. Participants or their legal representative, as well as the participant's caregiver, must be able to provide written informed consent.
The study will consist of a screening visit (up to 4 weeks prior to first dose), a 26-week double blind treatment period, and an end-of-study (EOS) visit. In the event a participant discontinues treatment or the study prematurely, the participant will be asked to return for an early termination (ET) visit for safety assessments. These assessments are the same as those done at the EOS visit.
Prior to randomization, eligibility of potential participants will be confirmed through an adjudication process in which screening data (eg, MMSE) obtained to evaluate AD status are reviewed by a central independent adjudicator. The adjudicator will review the scoring sheet completed by the Investigator prior to randomization and provide an independent assessment of the participant's eligibility and may request exclusion of a participant from entry into the study. A central independent reader will review magnetic resonance imaging (MRI) or computed tomography (CT) scans or reports to confirm eligibility. Investigators must not randomize a participant prior to receipt of this independent confirmation of the participant's eligibility.
Eligible participants will be randomized to treatment with either GV1001 0.56 mg, GV1001 1.12 mg, or placebo (normal saline) in a 1:1:1 ratio. Study treatment (GV1001 0.56 mg, GV1001 1.12 mg, or placebo) will be administered by subcutaneous (SC) injection every week for 4 weeks (4 times) followed by SC administration every 2 weeks through Week 24 (10 times) for a total of 14 SC administrations of study treatment.
Efficacy evaluations will be performed at baseline, Week 12, and Week 26 using the Mini-Mental State Examination (MMSE), Alzheimer's Disease Assessment Scale-cognitive (ADAS cog), Clinician's Interview-Based Impression of Change (CIBIC)-Plus, Clinical Dementia Rating - Sum of Boxes (CDR-SB), Alzheimer's Disease Cooperative Study-Activities of Daily Living scale (ADCS-ADL), and Neuropsychiatric Inventory (NPI) scales. The efficacy evaluations are to be done in the same order at each visit. To ensure the objectivity and accuracy of the study results, efficacy evaluations must be performed by adequately trained and experienced clinicians. The raters must be certified for this study to administer the Mini-Mental State Examination (MMSE), Alzheimer's Disease Assessment Scale-cognitive (ADAS cog), Clinician's Interview-Based Impression of Change (CIBIC)-Plus, Clinical Dementia Rating - Sum of Boxes (CDR-SB), Alzheimer's Disease Cooperative Study-Activities of Daily Living scale (ADCS-ADL), and Neuropsychiatric Inventory (NPI) scales. Training, certification, and materials for rating will be provided by a rater training group. To mitigate the risk of breaking the blind, the efficacy evaluator is not to be involved in the participant's treatment or have access to the record of reported Adverse Events (AEs).
Safety will be assessed throughout the study by monitoring for AEs, laboratory evaluations, electrocardiogram (ECG) findings, vital sign measurements, and suicidal ideation and behavior (C-SSRS). Pharmacodynamics will be evaluated by collecting blood and cerebrospinal fluid (CSF) for analysis of biomarkers of AD. Blood samples will also be collected for pharmacokinetic (PK) and immunogenicity analysis, including determination of GV1001 plasma concentrations (sparse PK) and antibodies to GV1001.
Study Type : | Interventional (Clinical Trial) |
Estimated Enrollment : | 90 participants |
Allocation: | Randomized |
Intervention Model: | Parallel Assignment |
Masking: | Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor) |
Primary Purpose: | Treatment |
Official Title: | A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel Design, Prospective, Phase IIa Clinical Trial to Evaluate the Safety and Efficacy of GV1001 Administered Subcutaneously for the Treatment of Moderate Alzheimer's Disease |
Estimated Study Start Date : | September 1, 2019 |
Estimated Primary Completion Date : | August 31, 2021 |
Estimated Study Completion Date : | February 28, 2022 |
Arm | Intervention/treatment |
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Placebo Comparator: Placebo
Placebo SC injection administered once weekly for 4 weeks then every 2 weeks through Week 24
|
Drug: Normal saline
0.9% normal saline
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Experimental: GV1001 0.56 mg
GV1001 0.56 mg SC injection administered once weekly for 4 weeks then every 2 weeks through Week 24
|
Drug: GV1001
Lyophilized peptide from hTERT
Other Name: Tertomotide
|
Experimental: GV1001 1.12 mg
GV1001 1.12 mg SC injection administered once weekly for 4 weeks then every 2 weeks through Week 24
|
Drug: GV1001
Lyophilized peptide from hTERT
Other Name: Tertomotide
|
Ages Eligible for Study: | 55 Years to 85 Years (Adult, Older Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
Inclusion Criteria:
Has a caregiver who:
A female participant is eligible to participate if she is not pregnant (see Appendix 4), not breastfeeding, and at least one of the following conditions applies:
Exclusion Criteria:
Any other cause of dementia shown by MRI/CT findings and neurological examination within 12 months of randomization.
Contact: Eujin Hyun, Ph.D. | +82317085566 | clinical@gemvax.com |
Tracking Information | |||||
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First Submitted Date ICMJE | May 8, 2019 | ||||
First Posted Date ICMJE | May 22, 2019 | ||||
Last Update Posted Date | May 28, 2019 | ||||
Estimated Study Start Date ICMJE | September 1, 2019 | ||||
Estimated Primary Completion Date | August 31, 2021 (Final data collection date for primary outcome measure) | ||||
Current Primary Outcome Measures ICMJE |
Alzheimer's Disease Assessment Scale-cognitive (ADAS-cog) [ Time Frame: Week 26 ] The proportion of participants with any improvement in ADAS-cog compared to the baseline and Week 26
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Original Primary Outcome Measures ICMJE | Same as current | ||||
Change History | |||||
Current Secondary Outcome Measures ICMJE |
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Original Secondary Outcome Measures ICMJE | Same as current | ||||
Current Other Pre-specified Outcome Measures | Not Provided | ||||
Original Other Pre-specified Outcome Measures | Not Provided | ||||
Descriptive Information | |||||
Brief Title ICMJE | GV1001 Subcutaneous(SC) for the Treatment of Moderate Alzheimer's Disease (AD) | ||||
Official Title ICMJE | A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel Design, Prospective, Phase IIa Clinical Trial to Evaluate the Safety and Efficacy of GV1001 Administered Subcutaneously for the Treatment of Moderate Alzheimer's Disease | ||||
Brief Summary | The current study is being conducted by the Sponsor to evaluate the efficacy and safety of GV1001 (0.56 mg and 1.12 mg) administered subcutaneously as a treatment for moderate Alzheimer's disease (AD). GV1001 has been shown to inhibit neurotoxicity, apoptosis, and the production of reactive oxygen species induced by amyloid beta 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 has been shown to improve cognitive function and memory, as well as significantly reduce the amount of amyloid beta and tau proteins. The multifunctional effect of GV1001 makes it a promising therapeutic option for the treatment for AD. | ||||
Detailed Description |
This is a multicenter, randomized, double-blind, placebo-controlled, dose finding, parallel-group Phase IIa study in participants with moderate AD. The study population will be comprised of male and female participants between 55 and 85 years of age, inclusive, with a diagnosis of probable AD based on National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association (NINCDS ADRDA) criteria. Participants must also meet Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-V) criteria for dementia and have an Mini-Mental State Examination (MMSE) score ≥10 to <20. Participants or their legal representative, as well as the participant's caregiver, must be able to provide written informed consent. The study will consist of a screening visit (up to 4 weeks prior to first dose), a 26-week double blind treatment period, and an end-of-study (EOS) visit. In the event a participant discontinues treatment or the study prematurely, the participant will be asked to return for an early termination (ET) visit for safety assessments. These assessments are the same as those done at the EOS visit. Prior to randomization, eligibility of potential participants will be confirmed through an adjudication process in which screening data (eg, MMSE) obtained to evaluate AD status are reviewed by a central independent adjudicator. The adjudicator will review the scoring sheet completed by the Investigator prior to randomization and provide an independent assessment of the participant's eligibility and may request exclusion of a participant from entry into the study. A central independent reader will review magnetic resonance imaging (MRI) or computed tomography (CT) scans or reports to confirm eligibility. Investigators must not randomize a participant prior to receipt of this independent confirmation of the participant's eligibility. Eligible participants will be randomized to treatment with either GV1001 0.56 mg, GV1001 1.12 mg, or placebo (normal saline) in a 1:1:1 ratio. Study treatment (GV1001 0.56 mg, GV1001 1.12 mg, or placebo) will be administered by subcutaneous (SC) injection every week for 4 weeks (4 times) followed by SC administration every 2 weeks through Week 24 (10 times) for a total of 14 SC administrations of study treatment. Efficacy evaluations will be performed at baseline, Week 12, and Week 26 using the Mini-Mental State Examination (MMSE), Alzheimer's Disease Assessment Scale-cognitive (ADAS cog), Clinician's Interview-Based Impression of Change (CIBIC)-Plus, Clinical Dementia Rating - Sum of Boxes (CDR-SB), Alzheimer's Disease Cooperative Study-Activities of Daily Living scale (ADCS-ADL), and Neuropsychiatric Inventory (NPI) scales. The efficacy evaluations are to be done in the same order at each visit. To ensure the objectivity and accuracy of the study results, efficacy evaluations must be performed by adequately trained and experienced clinicians. The raters must be certified for this study to administer the Mini-Mental State Examination (MMSE), Alzheimer's Disease Assessment Scale-cognitive (ADAS cog), Clinician's Interview-Based Impression of Change (CIBIC)-Plus, Clinical Dementia Rating - Sum of Boxes (CDR-SB), Alzheimer's Disease Cooperative Study-Activities of Daily Living scale (ADCS-ADL), and Neuropsychiatric Inventory (NPI) scales. Training, certification, and materials for rating will be provided by a rater training group. To mitigate the risk of breaking the blind, the efficacy evaluator is not to be involved in the participant's treatment or have access to the record of reported Adverse Events (AEs). Safety will be assessed throughout the study by monitoring for AEs, laboratory evaluations, electrocardiogram (ECG) findings, vital sign measurements, and suicidal ideation and behavior (C-SSRS). Pharmacodynamics will be evaluated by collecting blood and cerebrospinal fluid (CSF) for analysis of biomarkers of AD. Blood samples will also be collected for pharmacokinetic (PK) and immunogenicity analysis, including determination of GV1001 plasma concentrations (sparse PK) and antibodies to GV1001. |
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Study Type ICMJE | Interventional | ||||
Study Phase ICMJE | Phase 2 | ||||
Study Design ICMJE | Allocation: Randomized Intervention Model: Parallel Assignment Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor) Primary Purpose: Treatment |
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Condition ICMJE | Moderate Alzheimer's Disease | ||||
Intervention ICMJE |
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Study Arms ICMJE |
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Publications * | Not Provided | ||||
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline. |
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Recruitment Information | |||||
Recruitment Status ICMJE | Not yet recruiting | ||||
Estimated Enrollment ICMJE |
90 | ||||
Original Estimated Enrollment ICMJE | Same as current | ||||
Estimated Study Completion Date ICMJE | February 28, 2022 | ||||
Estimated Primary Completion Date | August 31, 2021 (Final data collection date for primary outcome measure) | ||||
Eligibility Criteria ICMJE |
Inclusion Criteria:
Exclusion Criteria:
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Sex/Gender ICMJE |
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Ages ICMJE | 55 Years to 85 Years (Adult, Older Adult) | ||||
Accepts Healthy Volunteers ICMJE | No | ||||
Contacts ICMJE |
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Listed Location Countries ICMJE | Not Provided | ||||
Removed Location Countries | |||||
Administrative Information | |||||
NCT Number ICMJE | NCT03959553 | ||||
Other Study ID Numbers ICMJE | KG7/2017 | ||||
Has Data Monitoring Committee | No | ||||
U.S. FDA-regulated Product |
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IPD Sharing Statement ICMJE |
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Responsible Party | GemVax & Kael | ||||
Study Sponsor ICMJE | GemVax & Kael | ||||
Collaborators ICMJE | Not Provided | ||||
Investigators ICMJE | Not Provided | ||||
PRS Account | GemVax & Kael | ||||
Verification Date | May 2019 | ||||
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP |