| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Mild to moderate Alzheimer disease |
|
| MedDRA Classification |
| 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 |
The primary objectives of this study are to assess the safety and efficacy of VP4896 in the treatment of mild-to-moderate Alzheimer's disease (AD) as measured by:
- Difference from placebo in the scores on the ADAS-Cog and the ADCS-CGIC at 50 weeks compared to baseline.
- The incidence of AEs and clinically significant changes in laboratory values, ECGs, vital signs, and physical examinations over 56 weeks. |
|
| E.2.2 | Secondary objectives of the trial |
The secondary objectives of this study are:
- To assess the efficacy of VP4896 compared to placebo as measured by change from baseline in NPI, ADCS-CGIS, and ADCS-ADL at 50 weeks |
|
| E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
| E.3 | Principal inclusion criteria |
Male and female subjects will be considered eligible if:
1. they give their consent by signing the IRB/EC-approved Informed Consent Form/Patient Information Form and the responsible caregiver also signs the consent form; or, if the subject is judged by the Investigator to be unable to give consent, but the legally authorized representative gives consent by signing the consent form and the subject gives assent, in accord with local regulations;
2. they are 65 years of age or older;
3. they have a diagnosis of probable AD according to the National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA) criteria;
4. they have been on a stable dose of an acetylcholinesterase inhibitor (including, but not limited to: donepezil, galantamine, rivastigmine and tacrine) for at least 120 days prior to baseline and, in the Investigator's opinion, the dosage will likely remain stable throughout the trial;
5. they are taking other medications for the treatment of Alzheimer's Disease such as memantine; however, they must be on a stable dose for at least 120 days prior to baseline and, in the Investigator's opinion, the dosage will likely remain stable throughout the trial;
6. they are taking other drugs or substances that have purported cognition enhancing properties, such as ginkgo biloba or Vitamin E, and they began taking it at least 60 days prior to baseline and, in the Investigator's opinion, the dosage will likely remain stable throughout the trial;
7. their score on the MMSE is 12 to 24, inclusive, at the screening visit;
8. they have had brain imaging after the onset of dementia consistent with a diagnosis of AD and not of vascular origin;
9. their Rosen Modified Hachinski score was 4 or lower at the screening visit, supporting the Investigator's clinical judgment that the subject's dementia is probable AD and not of vascular origin;
10. they have completed at least 6 years of education;
11. they live at home or in a congregate living facility for requirements other than skilled nursing care, and have a caregiver who sees the subject at least three times a week for a total of at least 10 hours and who can sign the consent form, provide information pertinent to the subject's cognitive status, accompany the subject on clinic visits and participate in the evaluations for the duration of the study;
12. their score on the Cornell Scale for Depression in the Dementia (CSDD) is less than 12 at the screening visit;
13. values on their screening laboratory tests do not indicate significant medical conditions that would interfere with their participation in and completion of the study.
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|
| E.4 | Principal exclusion criteria |
Subjects will be declared ineligible if:
1. they have significant neurological disease affecting the brain or psychiatric disease other than AD, such as current untreated major depression, schizophrenia, epilepsy, Parkinson's disease, Creutzfeldt-Jacob's disease, or clinical episode stroke;
2. the screening ECG shows evidence of a serious and/or unstable condition as determined by the Investigator;
3. they have laboratory or clinical signs of untreated, clinically significant abnormal thyroid function, in the Investigator's opinion;
4. they have clinically significant folic acid or B12 abnormalities detected within 1 year of study entry. History of such laboratory abnormalities will require additional assessments to determine eligibility.
5. they have current evidence of pernicious anemia, history or current evidence of luetic brain disease (established by serology and other procedures), or other chronic infections of the central nervous system. Positive VDRL and/or FTA-ABS acceptable if luetic brain disease excluded by documented studies and/or treatment;
6. they started or changed within 60 days prior to the baseline visit, the dosage of any drug (including OTC) that affects cognitive function, such as antipsychotics, antidepressants, anxiolytics, sedatives, hypnotics, anti-convulsants, centrally acting hypersensitive agents such as clonidine and Aldomet; or other medications that have been shown to have possible effects on cognition such as Vitamin E, non-steroidal anti-inflammatory drugs, and statins, or if, in the Investigator’s opinion, the dosage of such medication is likely to be changed during the course of this trial. Such medications may be taken providing they were started greater than 60 days prior to baseline and the dose is likely to remain stable.
7. they are receiving coumadin or anti-Parkinsonian medications;
8. they have received other investigational drugs within 30 days or 5 half-lives prior to baseline, whichever is longer;
9. they have a known hypersensitivity to leuprolide or drugs similar to leuprolide;
10. with the exception of estrogen, they are taking other medications known to affect serum gonadotropin (Gn) concentrations, including, but not limited to gosorelin, danazol or leuprolide;
11. their abuse of or dependence on alcohol or other substances satisfy criteria for DSM-IV categories 303.9 or 305 within the past year;
12. they have donated blood within 30 days of baseline or are likely to do so during the course of the trial;
13. they have an history of cancer within the last 5 years, except for basal cell or squamous cell cancer of the skin;
14. they have participated in a previous clinical trial of leuprolide for AD or have had an extended course of leuprolide treatment for other conditions;
15. they are male and have clinically significant bladder outlet obstruction, unless, in the opinion of the Investigator, the condition is effectively managed with Hytrin®, Flomax®, or other medication.
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| E.5 End points |
| E.5.1 | Primary end point(s) |
| Primary efficacy parameters are the change form baseline in the ADAS-Cog score at Week 50 and the change form baseline in global severity of illeness as reflected in the ADCS-CGIC score at Week 50 |
|
| 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 | Information not present in EudraCT |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| 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) | No |
| E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
| 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.8.3 |
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.8.5 | The trial involves multiple Member States | Yes |
| 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 | Information not present in EudraCT |
| 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 |
|
| E.8.7 | Trial has a data monitoring committee | Information not present in EudraCT |
| 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
|
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 4 |
| E.8.9.1 | In the Member State concerned months | |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial years | 4 |
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