E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 5.1 |
E.1.2 | Level | HLT |
E.1.2 | Classification code | 10001897 |
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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 assess the safety and tolerability of multiple doses of AAB-001 in patients with mild to moderate Alzheimer’s disease (AD).
To evaluate the effect of AAB-001 on brain amyloid burden in patients with mild to moderate AD. |
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E.2.2 | Secondary objectives of the trial |
To evaluate the efficacy of AAB-001 in patients with mild to moderate AD. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Signed and dated written informed consent obtained from the patient and/or the patient’s legally acceptable representative, if applicable, in accordance with the local regulations. 2. Diagnosis of Probable Alzheimer’s disease according to National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer’s Disease and Related Disorders Association (NINCDS/ADRDA) criteria. 3. Age from 50 to 80 years, inclusive. 4. Mini-Mental State Examination (MMSE) score of 18-26. 5. Rosen Modified Hachinski Ischemic score <=4. 6. Lives at home with appropriate caregiver capable of accompanying the patient on all clinic visits, or community dwelling with caregiver capable of accompanying patient on all clinic visits and visiting with patient approximately 5 times per week for the duration of the study. 7. Screening visit MRI (magnetic resonance imaging) scan consistent with the diagnosis of AD and determined to be of sufficient quality for brain volumetric analyses. 8. Fluency in local language and evidence of adequate premorbid intellectual functioning. Patient must have adequate visual and auditory abilities to perform all aspects of the cognitive and functional assessments. 9. Receiving stable doses of medications for the treatment of non-excluded medical conditions for at least 30 days prior to screening. If a patient is taking acetylcholinesterase inhibitors and/or memantine, then these medication(s) must be maintained on a stable dose regimen for at least 120 days prior to screening evaluations. 10. Likely to be able to participate in all scheduled evaluations and complete all required tests. 11. In the opinion of the investigator, the patient and the caregiver will be compliant and have a high probability of completing the study. 12. Measurable amyloid burden on the screening PIB PET scan with PIB retention in the range expected for AD patients. Defined as 3 of the 5 target regions (anterior cingulate, posterior cingulate, frontal cortex, temporal cortex and parietal cortex) having a ratio of target region radioactivity (kBq/ml) over reference region radioactivity (cerebellar grey matter) >1.5. Patients with a previous PIB PET scan may be eligible to enter the study, subject to fulfilling the required local and/or national radiation safety exposure requirements. |
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E.4 | Principal exclusion criteria |
1. Significant neurological disease other than AD that may affect cognition. 2. Current presence of a clinically significant major psychiatric disorder (e.g., Major Depressive Disorder) according to the criteria of the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV), or any symptom (e.g., hallucinations), that could affect the patient’s ability to complete the study. 3. Current clinically significant systemic illness that is likely to result in deterioration of the patient’s condition or affect the patient’s safety during the study. 4. History of clinically evident stroke or history of clinically significant carotid or vertebrobasilar stenosis or plaque. 5. History of seizures, excluding febrile seizures in childhood. 6. Weight greater than 120 kg (264 lbs). 7. History or evidence of any significant autoimmune disease or disorder of the immune system. 8. Clinically significant infection within the last 30 days (e.g., chronic persistent or acute infection). 9. Treatment with immunosuppressive medications (e.g., systemic corticosteroids) within the last 90 days (topical and nasal corticosteroids and inhaled corticosteroids for asthma are permitted) or chemotherapeutic agents for malignancy within the last 3 years. 10. Myocardial infarction within the last 2 years. 11. History of cancer within the last 5 years, with the exception of basal cell carcinoma, and nonmetastatic squamous cell carcinoma of the skin. 12. Other clinically significant abnormality on physical, neurological, laboratory, or ECG examination (e.g., atrial fibrillation) that could compromise the study or be detrimental to the patient. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The incidence and severity of treatment-emergent adverse events (TEAEs);
Clinically important changes in safety assessment results (including, as appropriate, vital signs, weight, clinical laboratory tests, electrocardiograms [ECGs], MRIs, and physical and neurological exams);
Change from screening brain amyloid burden at Weeks 20, 45, and 78 on PET, Pittsburgh Compound B (PIB) an amyloid binding agent.
Change from screening in regional cerebral metabolic rates for glucose at Week 78 on PET using fluoro-deoxyglucose (FDG). |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | Information not present in EudraCT |
E.6.2 | Prophylaxis | Information not present in EudraCT |
E.6.3 | Therapy | Information not present in EudraCT |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | Information not present in EudraCT |
E.6.9 | Dose response | Information not present in EudraCT |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | Information not present in EudraCT |
E.6.12 | Pharmacoeconomic | Information not present in EudraCT |
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.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 3 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
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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The end of the study will be defined as the date of the last subject’s visit. The sponsor will adhere to the timeframes outlined within Directive 2001/20/EC for the notifications of study completion or early termination and provision of study reports to ECs and Competent Authorities. |
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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 | 6 |
E.8.9.1 | In the Member State concerned days | |
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 | 6 |