E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
The most common form of dementia, i.e. the serious loss of global cognitive ability in a previously unimpaired person, beyond what might be expected from normal aging |
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E.1.1.2 | Therapeutic area | Psychiatry and Psychology [F] - Mental Disorders [F03] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 17.0 |
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 a 12-month treatment of RO4602522 versus placebo added to AChEI alone or in combination with memantine in patients with moderate severity AD (MMSE 13-20 inclusive), based on mean change in ADAS-Cog-11 scores (cognitive endpoint) from baseline over time. |
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E.2.2 | Secondary objectives of the trial |
• Effect on cognition assessed with the ADAS-Cog-11 scale
• Effect on functioning assessed with the ADCS-ADL scale
• Effect on behavioral symptoms
• Effect on the global measures assessed with the ADCS-CGIC scale and the Global Deterioration Scale (GDS).
• Assessment of safety and tolerability
• Estimating population-PK parameters and investigating the influence of various covariates on these parameters.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Probable AD, based on the National Institute of Neurological and Communicative Disorders and Stroke (NINCDS)/Alzheimer’s Disease and Related Disorders Association (ADRDA) and DSM-IV-TR criteria.
2. 50-90 years of age
3. MMSE score at screening between 13 and 20, inclusive
4. MRI supports a diagnosis of AD, with no evidence of other disease likely to account for the subject’s dementia.
5. Body mass index (BMI) between 18 and 36.
6. Modified Hachinski Ischemia Score of ≤4.
7. Patients with CSDD scores ≤13.
8. Receiving treatment with donepezil, rivastigmine, galantamine or any of these AChEIs in combination with memantine for at least 4 months, with their dose and formulation stabilized for at least 3 months prior to screening. All formulation and dosages are allowed except donezepil 23 mg (alone or in combination).
9. Generally healthy and ambulatory or ambulatory-aided (i.e., walker or cane).
10. Have a caregiver who has frequent contact with the patient, who is considered reliable, who can accompany patient to study visits and help with protocol procedures, and who is also able and willing to provide input for completing the caregiver scales and sign the caregiver consent form.
11. Females of childbearing potential must have a negative pregnancy test and must agree to use effective contraception |
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E.4 | Principal exclusion criteria |
1. Any neurological or psychiatric condition that may currently or during the course of the study impair cognition or functioning that is not associated with Alzheimer's disease
2. Background of mental retardation
3. At risk of suicide
4. Uncontrolled behavioral symptoms
5. Alcohol and/or substance abuse or dependence in the past 2 years, except nicotine use
6. Preexisting neuropathy
7. Unstable or poorly controlled hypertension and/or cardiovascular disease
8. Clinically relevant ECG abnormality
9. Bradycardia
10. Aspartate aminotransferase, alanine aminotransferase or total bilirubin ≥1.5 times the upper limit of normal
11. HIV positive, history of Hepatitis B infection within the past year, or history of Hepatitis C infection
12. Hepatitis B virus surface Antigen (HBsAg) and/or Hepatitis C antibodies (HepCAb) positive
13. Abnormal thyroid function tests
14. Poorly controlled diabetes
15. Severe renal impairment
16. Requiring nursing home care. Patients living in assisted living facilities are allowed if a reliable caregiver is available (see inclusion criteria)
17. History of cancer except if considered likely to be cured as documented by an oncologist / surgeon or in the case of non-melanoma skin cancers and prostate adenocarcinoma if there has been no significant progression over the last 2 years
18. Involvement in any other investigational trial in the last 3 months
19. Current treatment for AD other than those listed in inclusion criteria
20. Participation at any time in an active AD vaccine study
21. Participation in a passive AD immunization study less than 1 year before screening, with exceptions as per protocol
22. Recent (≤ 12 weeks) use of MAO inhibitors
23. Antidepressant treatment recently initiated (≤ 6 weeks).
24. Psychotropic medication as defined by protocol
25. Unwilling/ Unable to avoid ingesting food with high tyramine content (yeast concentrate, soy sauce, aged overripe cheese or very salty food)
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E.5 End points |
E.5.1 | Primary end point(s) |
The change from baseline in ADAS-Cog-11 over 12 months. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
following 12-month treatment (compared to baseline) |
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E.5.2 | Secondary end point(s) |
Mean ADCS-CGIC score, the mean change from baseline over time in ADCS-ADL, BEHAVE-AD-FW, AES and GDS scores, and the proportion of patients worsening over time in BEHAVE-AD-FW and ADCS-CGIC scores. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
following 12-month treatment (compared to baseline) |
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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 | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | Yes |
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
| Information not present in EudraCT |
E.8.4 | The trial involves multiple sites in the Member State concerned | Information not present in EudraCT |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 60 |
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 |
Australia |
Canada |
United States |
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E.8.7 | Trial has a data monitoring committee | No |
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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The end of the study will be considered to be the date of the last patient’s last visit (LPLV), including the last follow-up visit. |
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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 | 2 |
E.8.9.1 | In the Member State concerned months | 2 |
E.8.9.1 | In the Member State concerned days | 0 |
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 | 2 |
E.8.9.2 | In all countries concerned by the trial days | 0 |