A Study to Evaluate the Safety, Tolerability, and Efficacy of Long-Term Gantenerumab Administration in Participants With Alzheimer's Disease (AD)

Study Overview
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Brief Summary
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This is an open-label, multicenter, rollover study to evaluate the safety, tolerability, and efficacy of long-term administration of open-label gantenerumab in participants with AD who completed Study WN29922 or WN39658, either the double-blind or open-label extension (OLE) part.

Detailed Description
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Participants who were in the active arm in the double blind part and those who have completed OLE part in the parent study, will continue receive open-label gantenerumab 510 mg sub-cutaneously (SC) every 2 weeks (Q2W). Participants who are naive to gantenerumab treatment will be required to undergo the 3 step uptitration scheme as in the parent study before receiving target dose of open label gantenerumab.

Official Title
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An Open-Label, Multicenter, Rollover Study to Evaluate the Safety, Tolerability, and Efficacy of Long-Term Gantenerumab Administration in Participants With Alzheimer's Disease

Conditions
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Alzheimer Disease

Intervention / Treatment
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* Drug: Gantenerumab
* Drug: Gantenerumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Completed Study WN29922 or WN39658, either its double-blind part or OLE part, and did not discontinue study drug early The participant should be capable of completing assessments either alone or with the help of the caregiver Availability of a person (referred to as the caregiver) For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraception methods with a failure rate of <1% per year (bilateral tubal ligation, male sterilization, hormonal contraceptives that inhibit ovulation, hormone-releasing intrauterine devices, and copper intrauterine devices) 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 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 Any medical condition that 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 Evidence of disseminated 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
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group 1<br>Participants, who completed the double-blind part and did not enter the OLE part of Study WN29922 or WN39658, will be enrolled and receive open-label gantenerumab approximately 2 weeks after the Week 116 visit of Study WN29922 or WN39658. This will be considered the OLE baseline visit (OLE Day 1). | Drug: Gantenerumab<br>* Group 1 participants who were in the active arm in the double blind part in the parent study (WN29922 or WN39658), will continue to receive open-label gantenerumab 510 mg SC, Q2W. Participants who are naive to gantenerumab treatment will be required to undergo the 3 step uptitration scheme before receiving target dose of open label gantenerumab, 510 mg SC, Q2W.<br>|
| Experimental: Group 2<br>Participants, who completed the double-blind part and the OLE part of Study WN29922 or WN39658, will be enrolled and receive open-label gantenerumab approximately 2 weeks after the OLE Week 34 visit or the final dose visit in the Study WN29922 or WN39658 OLE. | Drug: Gantenerumab<br>* Group 2 participants who have completed OLE part in the parent study (WN29922 or WN39658), will continue to receive open-label gantenerumab 510 mg SC, Q2W<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs) |  | From Baseline (OLE Day 1) to Week 208 | 
| Change in Columbia-Suicide Severity Rating Scale (C-SSRS) Score |  | From Baseline (OLE Day 1) to Week 208 | 
| Percentage of Participants with Amyloid-Related Imaging Abnormalities-Edema (ARIA-E) Confirmed by Magnetic Resonance Imaging (MRI) |  | From Baseline (OLE Day 1) to Week 208 | 
| Percentage of Participants with Amyloid-Related Imaging Abnormalities-Haemosiderin deposition (ARIA-H) Confirmed by MRI |  | From Baseline (OLE Day 1) to Week 208 | 
| Percentage of Participants with Injection-Site Reactions (ISRs) |  | From Baseline (OLE Day 1) to Week 208 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Clinical Dementia Rating (CDR) Score |  | From Baseline (OLE Day 1) to Week 208 | 
| Change in Mini-Mental State Examination (MMSE) Score |  | From Baseline (OLE Day 1) to Week 208 | 
| Change in Alzheimer Disease Assessment Scale-Cognition, Subscale 11 (ADAS-Cog11) Score |  | From Baseline (OLE Day 1) to Week 208 | 
| Change in Alzheimer Disease Assessment Scale-Cognition, Subscale 13 (ADAS-Cog13) Score |  | From Baseline (OLE Day 1) to Week 208 | 
| Change in Verbal Fluency Task Score |  | From Baseline (OLE Day 1) to Week 208 | 
| Change in Coding |  | From Baseline (OLE Day 1) to Week 208 | 
| Change in Functional Activities Questionnaire (FAQ) Score |  | From Baseline (OLE Day 1) to Week 208 | 
| Change in Alzheimer Disease Cooperative Study Group-Activities of Daily Living (ADCS-ADL) Score |  | From Baseline (OLE Day 1) to Week 208 | 
| Percentage of Participants with Anti-drug Antibody (ADA) to Gantenerumab |  | From Baseline (OLE Day 1) to Week 208 |