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 | 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 |
The primary objective of the study is to assess the safety of solanezumab in patients with mild Alzheimer's disease (AD) patients during 24 months of open-label treatment (Study Period 1) following completion of 18 months of treatment with solanezumab or placebo in a double-blind registration study (H8A-MC-LZAM [LZAM] or H8A-MC-LZAN [LZAN], "feeder studies") through analysis of AEs, vital signs, laboratory evaluations, electrocardio grams (ECGs), and MRIs. The mild population is defined as patients with a feeder study Visit 1 MMSE score of 20 to 26.Is. |
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E.2.2 | Secondary objectives of the trial |
To test the hypothesis that solanezumab will slow the decline associated with AD during 24 mths of Period 1, comparing subjects randomized to solanezumab with subjects randomized to placebo in the feeder studies using ADAS-Cog14 & the MMSE. To assess the overall clinical benefit of treatment with solanezumab in AD pts during Period 1 of open-label treatment comparing pts randomized to solanezumab with pts randomized to placebo in feeder studies. Overall clinical benefit will be assessed through including the ADCS-ADL, the ADAS-Cog11, the CDR-SB, the NPI, RUD-Lite, the EQ-5D Proxy & the QoL–AD. To provide supporting evidence that solanezumab attenuates the underlying pathologic process in AD, as measured by changes in plasma Aβ levels & by using vMRI to assess the rate of decline in brain volumes during Period 1. To continue to assess the safety of solanezumab in Period 2. To assess the safety of solanezumab and disease progression in the moderate and overall populations. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
A patient included in the study must meet all of the following inclusion criteria. [1] Meets National Institute of Neurological and Communicative Disorders and Stroke/Alzheimer’s Disease and Related Disorders Association (NINCDS/ADRDA) criteria for probable AD (McKhann et al. 1984). [2] Has completed Study LZAM or Study LZAN through Visit 23. [3] Must continue to have a reliable caregiver who is in frequent contact with the patient (defined as at least 10 hours per week) and will accompany the patient to the office and/or be available by telephone at designated times. Note: The caregiver must be able to communicate with site personnel and be willing to comply with protocol requirements, and in the investigator’s opinion must have adequate literacy to complete the protocol-specified questionnaires. Participants living in an assisted-living facility may be included if regular contact with a caregiver who accompanies the patient is maintained. [4] Must have good venous access, such that intravenous drug delivery and multiple blood draws would be possible. [5] Agrees not to participate in studies of any other investigational compounds for the duration of Study LZAO. |
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E.4 | Principal exclusion criteria |
Patients will be excluded from the study if they meet any of the following criteria: [6] Are investigator site personnel directly affiliated with this study and/or their immediate families. Immediate family is defined as a spouse, parent, child, or sibling, whether biological or legally adopted. [7] Are Eli Lilly and Company (Lilly) employees. [8] Are currently enrolled in, or discontinued within the last 30 days from, a clinical trial involving an investigational drug or device or off-label use of a drug or device (other than the study drug/device used in this study), or concurrently enrolled in any other type of medical research judged not to be scientifically or medically compatible with this study. [9] Meets feeder study discontinuation criteria at the last visit of the feeder study (Study LZAO Visit 1). |
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E.5 End points |
E.5.1 | Primary end point(s) |
•Vital signs that are statistically different between treatment groups (LZAM and LZAN) [ Time Frame: 104 weeks ]
•Laboratory values that are statistically different between treatment groups (LZAM and LZAN)
•Electrocardiograms (ECGs) that are statistically different between treatment groups (LZAM and LZAN) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
•Change from baseline to 104 week endpoint in Alzheimer's Disease Assessment Scale—Cognitive subscore (ADAS-Cog) [Time Frame: Baseline, 104 weeks]
•Change from baseline to 104 week endpoint in Alzheimer's Disease Cooperative Study—Activities of Daily Living Inventory (ADCS-ADL) [Time Frame: Baseline, 104 weeks]
•Change from baseline to 104 week endpoint in Clinical Dementia Rating—Sum of Boxes (CDR-SB) [Time Frame: Baseline, 104 weeks]
•Change from baseline to 104 week endpoint in Neuropsychiatric Inventory (NPI) [ Time Frame: Baseline, 104 weeks]
•Change from baseline to 104 week endpoint in Resource Utilization in Dementia—Lite (RUD-Lite) [Time Frame: Baseline, 104 weeks]
•Change from baseline to 104 week endpoint in EuroQol 5-Dimensional Health-Related Quality of Life Scale Proxy version (EQ-5D Proxy) [Time Frame: Baseline, 104 weeks]
•Change from baseline to 104 week endpoint in Quality of Life in Alzheimer's Disease (QoL-AD) [Time Frame: Baseline, 104 weeks ]
•Change from baseline to 104 week endpoint in Mini-Mental State Examination (MMSE) [ Time Frame: Baseline, 104 weeks ]
•Change from baseline to 52 week endpoint in plasma Aβ levels [ Time Frame: Baseline, 52 weeks ]
•Change from baseline to 104 week endpoint in volumetric magnetic resonance imaging (vMRI) [Time Frame: Baseline, 104 weeks]
•Change from baseline to 80 week endpoint in amyloid plaque burden in the brain using positron emission tomography (PET) imaging [Time Frame: Baseline, 80 weeks] |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Time Frame: Basseline, 104 weeks Time Frame: Basseline, 52 weeks Time Frame: Basseline, 80 weeks |
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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 | No |
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 | No |
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 | 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.8.3 |
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 | 7 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 54 |
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 |
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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 | 4 |
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 | 5 |
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 |