E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
|
E.1.1.1 | Medical condition in easily understood language |
|
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 | 18.1 |
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 |
|
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 H8AMC- LZAN [LZAN], “feeder studies”) through analysis of AEs, vital signs, laboratory evaluations, electrocardiograms (ECGs), and MRIs. The mild population is defined as patients with a feeder study Visit 1 MMSE score of 20 to 26. |
|
E.2.2 | Secondary objectives of the trial |
- to test the hypothesis that solanezumab will slow decline associated with AD during OL treatment
- assess overall clinical benefit of solanezumab in AD patients during 24 months of OL treatment
- to provide supporting evidence that solanezumab attenuates the underlying pathologic progress in AD.
- to continue to assess the saftey of solanezumab in study Period 2 for patients who complete study period 1 and opt to participate in period 2.
- to continue to assess the saftey of solanezumab in study part 3 for patients who complete study period 2 and opt to participate in study period 3
- to continue to assess the saftey of solanezumab and disease progression in the moderate and overall populations. |
|
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. |
|
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). |
|
E.5 End points |
E.5.1 | Primary end point(s) |
- vital signs that are statistically different between treatment groups (LZAM and LZAN) (timeframe 104 weeks)
- laboratory values that are statistically different between treatment groups (LZAM and LZAN) (timeframe 104 weeks)
- Electrocardiograms (ECGs) that statistically different between treatment groups (LZAM and LZAN) (timeframe 104 weeks)
|
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
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 Aß 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] |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
Time Frame: Baseline, 104 weeks
Time Frame: Baseline, 52 weeks
Time Frame: Baseline, 80 weeks |
|
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 | 11 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 55 |
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 |
|
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
|
|
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 | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 8 |