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 |
To evaluate the long term safety and tolerability of IV administered bapineuzumab in subjects with Alzheimer's Disease.
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E.2.2 | Secondary objectives of the trial |
To demonstrate the maintenance of bapineuzumab clinical efficacy after 6 months of treatment in the extension study.
To demonstrate the effect of long-term treatment of IV administered bapineuzumab in subjects with AD on AD-related health outcomes (HO).
To evaluate the effect of bapineuzumab on three biomarkers which reflect the underlying disease pathology and pathophysiology
To assess the immunogenicity of long term treatment of IV administered bapineuzumab.
To evaluate the effect of long term treatment of IV administered bapineuzumab in subjects with
AD on AD-related health outcomes and behavioral measures.
To obtain data for potential interpretation of pharmacodynamic, efficacy, safety, and tolerability
measurements, as necessary, and to allow for the characterization of genetic factors associated
with AD in a subset of subjects. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
A subject must meet ALL of the following criteria to be considered for enrollment into this study:
1. Informed consent signed and dated by the caregiver, subject and/or by the subject’s legally acceptable representative according to local regulations.
2. Must have completed all 6 infusions unless they were required to temporarily suspend study drug (eg, due to VE or special technical or medical considerations), but continued with their required visits in either Study 301 or 302, and have completed Visit 15/Week 78. Subjects with fewer than 6 infusions in Study 301 or 302 must obtain medical monitor approval.
3. Brain MRI scan for the Radiologist to evaluate subject safety from Study 301 or 302 at Visit 14/Week71.
4. Continues to live at home or community dwelling with appropriate caregiver capable of accompanying the subject on all clinic visits and visiting with the subject approximately 5 times per week for the duration of the study.
5. In the opinion of the Principal Investigator, the risk:benefit ratio for participation in the trial is acceptable, the subject and the caregiver will be compliant, and likely to participate in all scheduled evaluations, and the caregiver will be a reliable informant.
6. CSF Participating Subjects only: Subjects must have completed a Visit 14/Week 71 lumbar puncture (LP) in the 301/302 Studies and consented to the CSF substudy in 351. |
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E.4 | Principal exclusion criteria |
ANY one of the following will exclude a subject from being enrolled into the study:
1. Any new medical contraindication or clinically significant abnormality on physical, neurological, laboratory, vital signs or electrocardiogram (ECG) examination (eg, atrial fibrillation) that precludes continued or initiation of treatment with bapineuzumab or participation in the study.
2. Screening visit brain MRI scan (ie, MRI from Study 301 or 302 Visit 14 /Week 71) indicative of any significant abnormality, including but not limited to history or evidence of a single prior hemorrhage >1 cm3, more than 4 microhemorrhages (<10 mm), or evidence of a single prior infarct >1 cm3, cerebral contusion, encephalomalacia, aneurysms, vascular malformations, subdural hematoma, or space occupying lesions (eg, brain tumors such as meningioma). NOTE: 351 Screening MRI Evaluation form is required on site prior to infusion. Subjects who have developed any of the above MRI abnormalities during Studies 301 or 302 may potentially be considered for Study 351 participation, however, approval by a medical monitor will be required prior to enrollment. An unblinded medical monitor may be used to exclude subjects with a history of any of the above MRI abnormalities or VE, if the MRI abnormalities, clinical findings or prior treatment assignment suggests potential safety concerns.
3. Current use of experimental medications for AD (other than bapineuzumab) and all other
experimental medications, and herbal preparations containing Ginkgo biloba. Current use of
anticoagulants (eg warfarin, heparin, enoxaparin, rivaroxaban, and apixaban) for any
indication. Current use of antiplatelet therapy (eg aspirin, clopidogrel, and dipyridamole) is
prohibited for stroke. Antiplatelet therapy for indications other than stroke prevention is
allowed. |
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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 vital signs,
weight, clinical laboratory tests, electrocardiograms (ECGs), brain MRI, physical and
neurological examinations, and infusion site assessments. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
End of Study or Early Termination |
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E.5.2 | Secondary end point(s) |
• Change from parent study baseline (Visit 2/Pre-Day 1) and extension study baseline (Visit
15/Week 78 of Study ELN115727-301 (Study 301) or ELN115727-302 (Study 302) over
time for the following scales: ADAS-Cog/11 and DAD
• Change from parent study baseline (Visit 2/Pre-Day 1) and extension study baseline (Visit
15/Week 78 of Study 301 or 302) over time for the following scale: DS
• Change from parent study baseline (visit 1/screening) and extension study baseline
(visit 15/week 78 of study 301 or 302) over time for the Mini-Mental State Examination
(MMSE).
• Amyloid brain amyloid burden imaged by 11C-PiB positron emission tomography (PET) in a
subset of subjects.
• Cerebrospinal Fluid (CSF) analysis to evaluate change in Aβ, total tau (t-tau) or phospho tau
(p-tau) levels over time CSF in a subset of subjects.
• Whole brain volume (WBV), whole brain boundary shift integral (BBSI), ventricular volume
(VV), ventricular boundary shift integral (VBSI), hippocampal volume (HCV), and
hippocampal BSI (HBSI) in a subset of subjects
• Serum anti-bapineuzumab antibody levels
• Change from Parent Study Baseline (Visit 2/Pre-Day 1) and Extension Study Baseline (Visit
15/Week 78 of Study 301 or 302) over time for the following scales: Abbreviated Resource Utilization in Dementia (Abbr. RUD Lite v2.4), Health Utilities Index (HUI), Neuropsychiatric Inventory (NPI)
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
End of Study or Early Termination |
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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 | Yes |
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 | No |
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 | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
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 | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 2 |
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 |
Canada |
Germany |
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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The study will last up to the time of commercial launch of bapineuzumab, or termination of the clinical trials program whichever comes first |
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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 | 3 |
E.8.9.1 | In the Member State concerned months | 3 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 4 |
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 |