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 |
Alzheimer's disease is a progressive disease beginning with mild memory loss possibly leading to loss of the ability to carry on a conversation and respond to the environment |
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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 | 10029205 - Nervous system disorders |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10074616 |
E.1.2 | Term | Prodromal Alzheimer's disease |
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 safety and tolerability of long-term gantenerumab administered by SC injection |
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E.2.2 | Secondary objectives of the trial |
• To evaluate the efficacy of long-term gantenerumab administered by SC injection
• To evaluate the immune response to gantenerumab administered by SC injection |
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
The substudies associated with Study WN42171 will be described in separate protocols, and patients consenting to enroll in these substudies
will be asked to sign the associated Informed Consent Forms.
- WN42171 Longitudinal Amyloid PET Substudy, version 1 dated 7-Mar-2020: LONGITUDINAL AMYLOID PET IMAGING SUBSTUDY ASSOCIATED WITH AN OPEN-LABEL, MULTICENTER, ROLLOVER STUDY TO EVALUATE THE SAFETY, TOLERABILITY, AND EFFICACY OF LONG-TERM GANTENERUMAB ADMINISTRATION IN PARTICIPANTS WITH ALZHEIMER'S DISEASE
- WN42171 Longitudinal Tau PET Substudy, version 1 dated 7-Mar-2020: EXPLORATORY LONGITUDINAL TAU PET IMAGING SUBSTUDY ASSOCIATED WITH AN OPEN LABEL, MULTICENTER, ROLLOVER STUDY TO EVALUATE THE SAFETY, TOLERABILITY, AND EFFICACY OF LONG-TERM GANTENERUMAB ADMINISTRATION IN PARTICIPANTS WITH ALZHEIMER'S DISEASE
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E.3 | Principal inclusion criteria |
• Completed Study WN29922 or WN39658, either its double-blind part (participants have reached the 510 mg Q2W dose schedule by the time of completion) or OLE part (participants have received at least 3 doses of 510 mg Q4W), and did not discontinue study drug early
• Ability to comply with the study protocol
• Willingness and ability to complete all aspects of the study (including MRI).
• Availability of a caregiver
• The participant should be capable of completing assessments either alone or with the help of the caregiver
• For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraception during the treatment period and for at least 16 weeks after the
final dose of gantenerumab
• Agreement not to donate blood or blood products for transfusion for the duration of the study and for 1 year after final dose of study drug |
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E.4 | Principal exclusion criteria |
• Pregnant or breastfeeding, or intending to become pregnant during the study or within at least 16 weeks after the final dose of study drug
• Prematurely discontinued from Study WN29922 or WN39658, either its double-blind or OLE part, as applicable, 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
• Received any investigational treatment other than gantenerumab during or since completion of Study WN29922 or WN39658, either its double-blind or OLE part, as applicable
• Evidence of disseminated leptomeningeal hemosiderosis (i.e., more than three focal leptomeningeal hemosiderosis)
• Evidence of intracerebral macrohemorrhage
• Use of prohibited medication
• Evidence of ARIA-E on the last MRI scan report in Study WN29922 or WN39658, either its double-blind or OLE part
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E.5 End points |
E.5.1 | Primary end point(s) |
1. Nature, frequency, severity, timing, and outcomes of adverse events and serious adverse events
2. Physical examinations (including neurologic systems), vital signs, ECG, laboratory tests, and Columbia-Suicide Severity Rating Scale (C-SSRS)
3. Nature, frequency, severity, and timing of ARIA-E and ARIA-H
4. Nature, frequency, severity, timing, and outcomes of ISRs
5. Incidence of treatment discontinuations for adverse events
6. Incidence of adverse events of special interest |
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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) |
Efficacy
1. Change over time in Clinical Dementia Rating (CDR)
2. Change over time in Mini-Mental State Examination (MMSE)
3. Change over time in Alzheimer Disease Assessment Scale-Cognition, Subscale 13 (ADASCog13) and Subscale 11 (ADAS-Cog11)
4. Change over time in Verbal Fluency Task
5. Change over time in Coding
6 Change over time in Functional Activities Questionnaire (FAQ)
7. Change over time in Alzheimer Disease Cooperative Study Group-Activities of Daily Living (ADCS-ADL)
Immunogenicity
8. Prevalence of anti-drug antibodies (ADAs) at baseline and incidence of ADAs during the study
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1-7. Baseline to Week 104
8. Up to Week 116
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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 | 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 | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
Immunogenicity, Biomarker, Health Status Utility |
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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 | Yes |
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 | Yes |
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.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 108 |
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 |
Australia |
Chile |
Mexico |
Peru |
Singapore |
Turkey |
Argentina |
Belgium |
Brazil |
Canada |
China |
Croatia |
Denmark |
Finland |
Germany |
Hungary |
Italy |
Japan |
Korea, Republic of |
Lithuania |
Netherlands |
Poland |
Portugal |
Russian Federation |
Spain |
Sweden |
Taiwan |
United Kingdom |
United States |
France |
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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 end of this study is defined as the date when the last participant, last visit, occurs or the date at which the last data point required for statistical analysis or safety follow-up is received from the last participant, whichever occurs later. The end of the study is expected to occur by the end of 2024. |
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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 | |
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 | 4 |
E.8.9.2 | In all countries concerned by the trial months | 5 |