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

Official Summary

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.

Study Design

• Study Type: INTERVENTIONAL
• Allocation: NON_RANDOMIZED
• Model: SINGLE_GROUP
• Masking: NONE
• Enrollment: 1,382 participants

Study Arms

• Group 1 (EXPERIMENTAL)
  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).
• Group 2 (EXPERIMENTAL)
  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.

Interventions

• DRUG: Gantenerumab — 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.
• DRUG: Gantenerumab — 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

Primary Outcomes

• Number of Participants With at Least One Adverse Event (AE) and Serious Adverse Event (SAE) (From Baseline (OLE Day 1) up to 14 weeks after the last dose (up to 134 weeks))
• Number of Participants With Post-baseline Suicidal Ideation or Suicidal Behavior as Measured Using Columbia-Suicide Severity Rating Scale (C-SSRS) Score (From Baseline (OLE Day 1) up to 14 weeks after the last dose (up to 134 weeks))
• Number of Participants With at Least One Amyloid-Related Imaging Abnormalities-Edema (ARIA-E) Confirmed by MRI (From Baseline (OLE Day 1) up to 14 weeks after the last dose (up to 134 weeks))
• Number of Participants With at Least One Amyloid-Related Imaging Abnormalities-Haemosiderin Deposition (ARIA-H) Confirmed by MRI (From Baseline (OLE Day 1) up to 14 weeks after the last dose (up to 134 weeks))
• Number of Participants With Injection-Site Reactions (ISRs) (From Baseline (OLE Day 1) up to 14 weeks after the last dose (up to 134 weeks))

Secondary Outcomes

• Change From Baseline Over Time in Clinical Dementia Rating - Global Score (CDR-GS) (Baseline (OLE Day 1), Weeks 24, 36, 52, 76 and 104)
• Change From Baseline Over Time in Clinical Dementia Rating (CDR) - Sum of Boxes (SB) (Baseline (OLE Day 1), Weeks 24, 36, 52, 76 and 104)
• Change From Baseline Over Time in Mini-Mental State Examination (MMSE) Score (Baseline (OLE Day 1), Weeks 24, 36, 52, 76 and 104)
• Change From Baseline Over Time in Alzheimer Disease Assessment Scale-Cognition, Subscale 11 (ADAS-Cog11) Score (Baseline (OLE Day 1), Weeks 24, 36, 52, 76 and 104)
• Change From Baseline Over Time in Alzheimer Disease Assessment Scale-Cognition, Subscale 13 (ADAS-Cog13) Score (Baseline (OLE Day 1), Weeks 24, 36, 52, 76 and 104)

Eligibility Criteria

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

Trial Locations

• Banner Alzheimer?s Institute, Phoenix, Arizona, United States
• Barrow Neurological Institute, Phoenix, Arizona, United States
• Banner Sun Health Research Insitute, Sun City, Arizona, United States
• Health Initiatives Research, PLLC, Fayetteville, Arkansas, United States
• Fullerton Neurology and Headache Center, Fullerton, California, United States
• Neurology Center of North Orange County, Fullerton, California, United States
• Irvine Center for Clinical Research, Irvine, California, United States
• Desert Valley Research, Redlands, California, United States
• Sutter Medical Group, Neurology, Sacramento, California, United States
• Syrentis Clinical Research, Santa Ana, California, United States
• ...and 10 more locations

Study Officials

• Clinical Trials — STUDY_DIRECTOR
  Hoffmann-La Roche

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