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 (SC) gantenerumab at target dose in participants with AD who received gantenerumab in open-label extension (OLEs) of Studies WN25203 or WN28745 |
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E.2.2 | Secondary objectives of the trial |
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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) were eligible to participate in Part 1 of the study
- For women of childbearing potential: agreement to remain abstinent 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
- Agreement to not donate blood or blood products for transfusion for the duration of the study and for 1 year after final dose of study drug will be needed for all participants
- Availability of a person (referred to as the “caregiver” throughout this protocol) who in the investigator’s judgement, has frequent and sufficient contact with the participant |
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E.4 | Principal exclusion criteria |
- 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
- Evidence of intracerebral macrohemorrhage
Eligibility in Part 2
- All participants who have completed Week 104 visit in Part 1 of the study and have not been discontinued from Part 1 of the study can continue to participate in Part 2 of the study
- The inclusion and exclusion criteria mentioned above are also applicable for Part 2 of the study. |
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E.5 End points |
E.5.1 | Primary end point(s) |
1. Incidence, nature, severity, and timing of adverse events and serious adverse events
2. Changes from baseline in vital signs, blood tests
3. Changes from baseline in electrocardiogram
4. Changes from baseline in the Columbia-Suicide Severity Rating Scale (C SSRS)
5. Incidence, nature, severity, and timing of magnetic resonance imaging (MRI) safety findings: amyloid-related imaging abnormality–edema/effusion (ARIA E) and amyloid-related imaging abnormality–hemosiderin depositions (ARIA H)
6. Incidence, nature, severity, and timing of injection-site reaction (ISRs)
7. Number and proportion of anti-drug antibody (ADA)-positive and ADA-negative participants during both the treatment and follow-up periods
8. Incidence of treatment discontinuations for adverse events
9. Incidence of adverse events of special interest |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
1. Up to 4 weeks after the last dose of the study drug
2. Baseline (Day 1) to 4 weeks after the last dose of the study drug
3. At baseline and unscheduled visit (UV)
4-5. Baseline, Week 24, Week 52, Week 76, Week 104, Week 128, Week 156, Week 180, Week 208, follow-up (FU)/ early termination (ET) visit, UV
6. Up to 4 weeks after the last dose of the study drug
7. Day 1, Week 52, Week 104, Week 156, Week 208, FU/ET visit
8-9. Up to 4 weeks after the last dose of the study drug |
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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 | Yes |
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.8.2.4 | Number of treatment arms in the trial | 1 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 32 |
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 |
Canada |
Chile |
Japan |
Korea, Republic of |
Mexico |
Russian Federation |
Turkey |
United States |
Belgium |
Denmark |
Italy |
Poland |
United Kingdom |
Netherlands |
Spain |
Switzerland |
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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 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 | 5 |
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 | 5 |