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 |
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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 | 14.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10012271 |
E.1.2 | Term | Dementia Alzheimer's type |
E.1.2 | System Organ Class | 10029205 - Nervous system disorders |
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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 |
The primary objective of study 3133K1-3003-WW is to evaluate the long term safety and tolerability of intravenously administered bapineuzumab in subjects with Alzheimer Disease (AD) based on adverse events, scheduled vital signs, electrocardiogram parameters, clinical laboratory tests, brain MRI scans, physical and neurological examinations, and infusion site assessment. In addition, the studies will be continuously monitored by an independent safety monitoring committee. |
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E.2.2 | Secondary objectives of the trial |
In order to explore the long-term effect of bapineuzumab in subjects with AD, exploratory efficacy measures in study 3003 will include Alzheimer’s Disease Assessment Scale - Cognitive Subscale (ADAS-Cog), Disability Assessment for Dementia (DAD), Mini Mental State Examination (MMSE), Neuropsychiatric Inventory (NPI) and health outcome assessments [Dependence Scale (DS), Resource Utilization in Dementia, version 2.4 (RUD Lite v2.4), and Health Utilities Index (HUI)].
For biomarker objectives: please refer to section E.2.3. / E.2.3.1.
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
Substudies are incorporated into the main protocol, and so do not have a separate title/date/version. Four substudies are included: a cerebrospinal fluid (CSF) substudy, a volumetric MRI substudy, a PET substudy and a biochemical characterization substudy.
Objectives:
To evaluate the effect of IV administered bapineuzumab on biomarkers in subsets of subjects with AD:
• Amyloid ([11-C]-Pittsburgh Compound B [PIB]) positron emission tomography (PET) imaging.
• Brain volumetrics by magnetic resonance imaging (MRI).
• Aβ in CSF and plasma, total tau and phospho-tau levels in CSF.
• Biochemical characterization of circulating bapineuzumab antibody will also be conducted using immunoaffinity chromatography from patient sera.
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E.3 | Principal inclusion criteria |
1. Signed and dated written informed consent obtained from the subject or the subject’s legally acceptable representative (if applicable) in accordance with the local regulations. The subject’s caregiver must also consent to participate in the study.
2. Subject has completed all 6 infusions planned in protocol 3133K1-3001; or, if the subject was required to temporarily suspend investigational product (e.g., due to vasogenic edema, adverse event, study suspension), he/she continued with required visits, has completed all study visits through the Week 78 visit and his/her current status indicates that he/she resumed or is eligible to resume investigational product.
NOTE: Subjects who developed vasogenic edema during study 3133K1-3001 may be considered for study 3133K1-3003 participation if the abnormality is resolved and the subject met criteria to resume investigational product. Medical monitor approval to resume investigational product infusions is required prior to enrollment.
3. Brain MRI scan from Week 71 of study 3133K1-3001 is available for local radiology and central radiology evaluation and remains consistent with the diagnosis of AD.
4. MMSE score ≥10 at screening (Week 78 of 3133K1-3001).
5. Continues to live at home or is community dwelling with appropriate caregiver capable of accompanying the subject on all clinic visits and visiting with the subject at least 5 days per week, on average for the duration of the study.
6. In the opinion of the principal investigator, the subject and the caregiver will be compliant, and likely to participate in all scheduled evaluations.
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E.4 | Principal exclusion criteria |
1. Any medical or psychiatric contraindication (e.g., suicidal ideation/behavior) or clinically significant abnormality on physical, neurological, laboratory, vital signs or electrocardiogram (ECG) examination (e.g., atrial fibrillation) that precludes continued or initiation of treatment with bapineuzumab, participation in the study or evaluation of the subject’s response.
2. Brain MRI scan from study 3133K1-3001 week 71 visit indicative of any significant abnormality, including including but not limited to more than 4 microhemorrhages (<10 mm), history or evidence of a single prior hemorrhage > 1 cm3, multiple lacunar infarct (two or more) or evidence of a single prior infarct > 1 cm3, evidence of a cerebral contusion, encephalomalacia, aneurysms, vascular malformations, subdural hematoma, or space occupying lesions (e.g., arachnoid cysts or brain tumors such as meningioma).
3. Use of any experimental medications, other than bapineuzumab, within the last 60 days prior to screening.
4. Current use of herbal preparations containing ginkgo biloba, or use of anticoagulants.
NOTE: Platelet anti-aggregants (e.g., the use of aspirin 325 mg/day or less, clopidogrel bisulfate, dipyridamole except for stroke) are allowed.
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E.5 End points |
E.5.1 | Primary end point(s) |
Adverse events, brain MRI scans, vital signs, ECG measurements, clinical laboratory tests, physical and neurological examinations, and infusion site assessment. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
At screening and Day 1, and once every 6 weeks thereafter |
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E.5.2 | Secondary end point(s) |
ADAS-Cog, DAD, NPI, MMSE, PIB and FDG PET imaging, Brain volumetrics by MRI, Aβ in CSF and plasma, total tau and phospho-tau levels in CSF |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
At Day 1, and once every 6 weeks thereafter |
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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 | 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 | 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 | No |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
Only 1 treatment gp, but data analysed according to treatment assigned in base study |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
No comparator or placebo, but data analysed according to treatment assigned in base study |
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E.8.2.4 | Number of treatment arms in the trial | 1 |
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 | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 142 |
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 |
Argentina |
Australia |
Austria |
Belgium |
Chile |
Croatia |
Finland |
France |
Germany |
Italy |
Japan |
Mexico |
Netherlands |
New Zealand |
Poland |
Portugal |
Serbia |
Slovakia |
Spain |
Sweden |
United Kingdom |
United States |
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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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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 7 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 7 |
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 |