E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Mild to Moderate (stage 4 and 5) Alzheimer's Disease |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Nervous System Diseases [C10] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10001896 |
E.1.2 | Term | Alzheimer's disease |
E.1.2 | System Organ Class | 100000004852 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
-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 -To evaluate the safety of GV1001 in participants with mild to moderate AD |
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E.2.2 | Secondary objectives of the trial |
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: • A-IADL-Q • CDR-SB • ADAS-cog11 • NPI • MMSE • ADCS-CGIC/CIBIC Plus • QoL-AD
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Male or female participants 55 to 85 years of age (both inclusive) at the time of signing the informed consent. 2. Diagnosis of probable AD based on NINCDS-ADRDA criteria as determined by a neurologist, geriatrician, psychiatrist, or clinician approved by the Sponsor or designee. 3. Mild or moderate dementia as evidenced by MMSE score ≥13 to ≤24 at screening (Visit 1). 4. Imaging studies (MRI or CT) within 2 years prior to screening that has findings consistent with AD and without any other disease that may cause dementia. 5. An Aβ PET scan or CSF examination performed within 2 years prior to screening with results consistent with the presence of amyloid pathology. 6. If receiving an approved medication for AD (ie, donepezil, galantamine, rivastigmine, memantine, or memantine/donepezil combination product), 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. 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. Able to visit the study center and undergo cognitive, functional, and other tests specified in the protocol. 9. Has a caregiver who agrees to accompany the participant, to supervise the participant’s compliance, sees the participant sufficiently to provide meaningful assessment of changes in participant behavior and function over time and provide information on safety and tolerability. 10. A male participant must agree to use a highly effective contraception method 11. A female participant is eligible to participate if she is not pregnant, not breastfeeding, and not a WOCBP or a WOBCP who agrees to use highly effective contraception method. 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. Written informed consent provided by participant (or legal representative) and caregiver prior to any study-specific procedures. 14. Participants in France must belong to a social security scheme. |
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E.4 | Principal exclusion criteria |
1. Any other cause of dementia shown by MRI/CT findings within 2 years of screening and neurological examination at screening and Day 1 2. Concurrent or history of clinically significant psychiatric conditions (eg, schizophrenia or bipolar affective disorder) that in the Investigator’s opinion prevents the participant from participating, or is likely to confound interpretation of drug effect or affect cognitive assessments. 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. 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. 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. Known allergies, hypersensitivity, or intolerance to GV1001 or similar products or excipients. 7. History of alcohol, substance abuse or dependence as per DSM-V criteria (except nicotine dependence) within the last 2 years. 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. 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. 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. 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. Previous treatment with GV1001. 13. Received an investigational product for AD within the last 6 months. 14. Participated in another clinical study within 4 weeks prior to this study. 15. Treated with aducanumab or participated in a clinical study with aducanumab. 16. Renal impairment (creatinine clearance [CrCL] <30 mL/min). 17. Severe liver dysfunction (alanine aminotransferase [ALT] or aspartate aminotransferase [AST] >2 times the upper limit of normal [ULN]). 18. Body weight ≤35 kg. 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. Any other reason that in the opinion of the Investigator would make the participant ineligible to participate or to complete this study. 21. Patients deprived of their liberty by a judicial or administrative decision, and/or persons under psychiatric care within the meaning of Article L1121 6 of the Public Health Code. |
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E.5 End points |
E.5.1 | Primary end point(s) |
- Change from baseline in ADAS-Cog11 score at Week 52 - Adverse events (AEs), laboratory test results (hematology, serum chemistry, and urinalysis), electrocardiogram (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) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
- Week 52 - during study duration |
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E.5.2 | Secondary end point(s) |
Secondary efficacy endpoints: • Change from baseline in A-IADL-Q score at Week 52 • Change from baseline in CDR-SB score at Week 52 • Clinical worsening, defined as ≥4 points change from baseline in the ADAS-cog11 score at Week 52 • Change from baseline in NPI score at Week 52 • Change from baseline in MMSE score at Week 52 • Change from baseline in ADCS-CGIC/CIBIC-Plus score at Week 52 • Change from baseline in QoL-AD score at Week 52
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
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E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 3 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 5 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 37 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
United States |
Finland |
France |
Poland |
Netherlands |
Spain |
Italy |
Portugal |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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last visit of last patient |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 11 |
E.8.9.1 | In the Member State concerned days | 2 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |