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 |
AD is a chronic neurodegenerative disease that destroys memory and other important mental functions.
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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 | 20.0 |
E.1.2 | Level | HLT |
E.1.2 | Classification code | 10001897 |
E.1.2 | Term | Alzheimer's disease (incl subtypes) |
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 |
To evaluate the long-term safety and tolerability of continued treatment with Subcutaneous gantenerumab at target dose in participants with AD who received gantenerumab in Open Label Extensions (OLEs) of Studies WN25203 or WN28745. |
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E.2.2 | Secondary objectives of the trial |
Exploratory Efficacy Objective: To assess the long-term clinical effect in participants with AD. The MMSE total score will be used to assess AD progression.
Exploratory Pharmacodynamic Biomarker Objective: To evaluate the long-term effect of gantenerumab in participants with AD by assessing: - MRI-derived measurements over time, such as volumetric changes in whole brain, ventricles, hippocampus, or other structures, in all participants - Plasma pharmacodynamic biomarkers over time |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
All participants who completed the OLEs of Studies WN25203 or WN28745 (i.e., latest version of protocol in their countries, and did not discontinue study drug early) are eligible to participate in this study.
Eligible participants must provide written consent signed by them or by the participant’s legally authorized representative before his or her participation in the study
For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods that result in a failure rate of 1% per year during the treatment period and for at least 16 weeks after the last dose of study drug.
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E.4 | Principal exclusion criteria |
Participants who meet any of the following criteria will not be eligible for this study:
- Prematurely discontinued from the OLEs of Studies WN25203 or WN28745 or from study drug for any reason - Any medical condition that the investigator or Sponsor determines may jeopardize the participant’s safety if he or she continues to receive study treatment - If the participant is unlikely to benefit from gantenerumab therapy, based on disease progression or other factors, or if study participation is otherwise not in the participant’s best interest, by determination of the investigator or Sponsor - Any investigational treatment other than gantenerumab during or since completion of the OLEs of Studies WN25203 or WN28745 - Pregnancy - Evidence of disseminated leptomeningeal hemosiderosis (i.e., more than three focal leptomeningeal hemosiderosis) - Evidence of intracerebral macrohemorrhage |
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E.5 End points |
E.5.1 | Primary end point(s) |
To evaluate the long-term safety and tolerability of continued treatment with SC gantenerumab at target dose in participants with AD who received gantenerumab in OLEs of Studies WN25203 or WN28745, the corresponding endpoints will be evaluated:
- Nature, frequency, severity, and timing of AEs and SAEs - Physical examinations (including neurological systems), vital signs, blood tests, ECGs, and C-SSRS - Nature, frequency, severity, and timing of MRI findings: ARIA-E and ARIA-H Nature, frequency, severity, and timing of injection-site reactions - Immunogenicity of long-term treatment with gantenerumab through the measurements of ADAs - Incidence of treatment discontinuations for AEs - Incidence of AEs of special interest
There will be no formal confirmatory efficacy analyses for this study. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
The safety analysis will be evaluated when the last participant, last visit (LPLV) occurs or the date on which the last data point required for safety follow-up is received from the last participant in the study. |
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E.5.2 | Secondary end point(s) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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 | No |
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 | 4 |
E.8.5 | The trial involves multiple Member States | No |
E.8.5.1 | Number of sites anticipated in the EEA | 24 |
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 |
Belgium |
Canada |
Chile |
Denmark |
Italy |
Japan |
Korea, Republic of |
Mexico |
Netherlands |
Poland |
Russian Federation |
Spain |
Switzerland |
Turkey |
United Kingdom |
United States |
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E.8.7 | Trial has a data monitoring committee | No |
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 study is defined as the date when the last participant, last visit (LPLV) occurs or the date on which the last data point required for safety follow-up is received from the last participant in the study. |
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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 | 3 |
E.8.9.1 | In the Member State concerned days | 31 |
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 | 7 |
E.8.9.2 | In all countries concerned by the trial days | 25 |