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

Alzheimer Disease Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT04339413
• Other study ID #: WN41874
• Status: Terminated
• Phase: Phase 3
• Start date: May 22, 2020
• Est. completion date: January 4, 2023

Study information

• Verified date: December 2023
• Source: Hoffmann-La Roche
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The main purpose of the study was to evaluate the safety and tolerability of long-term administration of gantenerumab in participants with AD. All participants who have completed the open-label extensions (OLEs) of studies WN25203 or WN28745 were enrolled in Part 1 of this study. Of these, participants who completed Week 104 visit in Part 1. Participants received open-label gantenerumab by subcutaneous (SC) injection every four weeks (Q4W) at the same dose as administered in the parent studies (part 1)/ Week 104 visit.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 116
• Est. completion date: January 4, 2023
• Est. primary completion date: January 4, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A and older

Eligibility

Inclusion Criteria:

• Part 1: Participants who completed the open-label extensions (OLEs) of studies WN25203 or WN28745 will be eligible to participate in Part 1 of the study

• Part 2: All participants who have completed Week 104 visit in Part 1 will be eligible for Part 2 of the study

• For Part 1 and Part 2:

• 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

• 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

• Availability of a person ('caregiver') who in the investigator's judgement, has frequent and sufficient contact with the participant

Exclusion Criteria:

• Prematurely discontinued from the OLEs of studies WN25203 or WN28745 or from study drug for any reason

• Any medical condition that 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

• 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

• Part 2: Participants who have been discontinued from Part 1 of the study

Related Conditions & MeSH terms

• Alzheimer Disease

Intervention

Drug:
• Gantenerumab
Gantenerumab was administered as SC injection Q4W.

Locations

Country	Name	City	State
Argentina	Instituto Neurologia Bs As	Ciudad Autonoma Buenos Aires
Australia	Heidelberg Repatriation Hospital; Medical and Cognitive Research Centre	Heidelberg West	Victoria
Australia	The Queen Elizabeth Hospital; Neurology	Woodville	South Australia
Canada	Centricity Research	Halifax	Nova Scotia
Canada	True North Clinical Research-Halifax	Halifax	Nova Scotia
Canada	Kawartha Centre - Redefining Healthy Aging	Peterborough	Ontario
Canada	Alpha Recherche Clinique	Quebec
Canada	Toronto Memory Program	Toronto	Ontario
Chile	Especialidades Medicas LYS	Santiago
Denmark	Rigshospitalet, Hukommelsesklinikken	København Ø
Italy	Azienda Ospedaliera Spedali Civili; Scienze Neurologiche	Brescia	Lombardia
Italy	IRCCS ?Centro S. Giovanni di Dio? Fatebenefratelli -UO Alzheimer	Brescia	Lombardia
Italy	Irccs Multimedica Santa Maria; Unita' Di Neurologia	Castellanza	Lombardia
Italy	Fondazione San Raffaele Del Monte Tabor; Dipartimento Di Neurologia	Milano	Lombardia
Italy	Nuovo Ospedale Civile S. Agostino-Estense; Clinica Neurologica ? Dipartimento di Neuroscienze	Modena	Emilia-Romagna
Japan	Juntendo University Urayasu Hospital; Neurology	Chiba
Japan	Medical Corporation Hakuyokai Kashiwado Hospital	Chiba
Japan	National Hospital Organization Hiroshima-Nishi Medical Center	Hiroshima
Korea, Republic of	Inha University Hospital	Incheon
Korea, Republic of	Ewha Womans University Hospital (Seoul)	Seoul
Korea, Republic of	Seoul St Mary's Hospital	Seoul
Mexico	Hospital Mexico Americano	Guadalajara	Mexico CITY (federal District)
Mexico	AVIX Investigación Clínica S.C	Monterrey	Nuevo LEON
Mexico	Hospital Universitario; Dr. Jose E. Gonzalez	Monterrey	Nuevo LEON
Netherlands	Brain Research Center B.V	Amsterdam
Poland	NZOZ NEURO-KARD Ilkowski i Partnerzy Sp. Partn. Lek	Pozna?
Poland	Centrum Medyczne NeuroProtect	Warszawa
Poland	Przychodnia Specjalistyczna PROSEN	Warszawa
Russian Federation	Saint Petersburg State Institution of Healthcare City Geriatric Medico-Social Center	Saint Petersburg	Sankt Petersburg
Russian Federation	FSMEI HPE ?Military Medical Academy n.a. S.M.Kirov"of Minist	Sankt-peterburg	Sankt Petersburg
Spain	Fundación ACE; Servicio de Neurología	Barcelona
Spain	Hospital del Mar; Servicio de Neurologia	Barcelona
Spain	Hospital General Universitario de Elche; Servicio de Neurología	Elche	Alicante
Spain	Hospital Universitario 12 de Octubre; Servicio de Neurologia	Madrid
Spain	Hospital Mutua De Terrasa; Servicio de Neurologia	Terrassa	Barcelona
Spain	Hospital Universitario Dr. Peset; Servicio de Neurologia	Valencia
Spain	Hospital Universitario la Fe; Servicio de Neurologia	Valencia
Switzerland	Felix Platter-Spital Medizin Geriatrie	Basel
Turkey	Istanbul University Istanbul School of Medicine; Neurology	Istanbul
Turkey	Dokuz Eylul University Medicine Faculty; Noroloji Departmani	Izmir
Turkey	Ondokuz Mayis University School of Medicine; Neurology	Samsun
United Kingdom	Llandough Hospital; Llandough Hospital Memory Team 3rd Floor Academic Building	Cardiff
United Kingdom	Imperial Memory Unit, Charing Cross Hospital; Level 10 West, Department of Neurosciences	London
United Kingdom	Campus for Ageing & Vitality; Clincal Ageing Research Unit	Newcastle
United Kingdom	Hollins Park Hospital	Warrington
United States	Senior Adults Specialty Research	Austin	Texas
United States	Neurology Clinic PC	Cordova	Tennessee
United States	Western Michigan University Homer Stryker M.D. School of Medicine Center for Clinical Research	Kalamazoo	Michigan
United States	Alzheimer's Memory Center	Matthews	North Carolina
United States	Accelerated Enrollment Solutions	Orlando	Florida
United States	California Neuroscience Research Medical Group, Inc	Sherman Oaks	California
United States	Richmond Behavioral Associates	Staten Island	New York
United States	Banner Sun Health Research Insitute	Sun City	Arizona
United States	University of South Florida	Tampa	Florida
United States	Bioclinica The Villages	The Villages	Florida
United States	Central States Research	Tulsa	Oklahoma

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Canada,  Chile,  Denmark,  Italy,  Japan,  Korea, Republic of,  Mexico,  Netherlands,  Poland,  Russian Federation,  Spain,  Switzerland,  Turkey,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)	An AE was defined as any untoward medical occurrence in a participant administered with gantenerumab and which does not necessarily have a causal relationship with gantenerumab. A Serious Adverse Event (SAE) is any significant hazard, contraindication, side effect that is fatal or life threatening; requires in-patient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; is medically significant or requires intervention to prevent one or other of the outcomes listed above, and which does not necessarily have a causal relationship with gantenerumab.	Baseline [Day 1] up to 4 weeks after the last dose of study drug (Up to Week 133)
Primary	Number of Participants With Change in Any Suicidal Ideation or Behavior as Assessed by Columbia-Suicide Severity Rating Scale (C-SSRS)	C-SSRS=assessment tool used to assess lifetime suicidality of a participant (at baseline) as well as any new instances of suicidality (C-SSRS since last visit). Structured interview prompts recollection of suicidal ideation, including intensity of ideation, behavior, & attempts with actual/potential lethality. Categories have binary responses (yes/no) & include Wish to be Dead; Non-specific Active Suicidal Thoughts; Active Suicidal Ideation with Any Methods (Not Plan) without Intent to Act; Active Suicidal Ideation with Some Intent to Act, without Specific Plan; Active Suicidal Ideation with Specific Plan and Intent, Preparatory Acts and Behavior; Aborted Attempt; Interrupted Attempt; Actual Attempt (non-fatal); Completed Suicide. Suicidal ideation/behavior is indicated by a "yes" answer to any of the listed categories. Score of 0= no suicide risk present. Score of 1 or higher= suicidal ideation/behavior. Number of participants with any suicidal ideation/behavior were reported.	Baseline (Day 1), up to Week 104
Primary	Number of Participants With Amyloid-Related Imaging Abnormalities-Edema (ARIA-E) AEs		Baseline [Day 1] up to 4 weeks after the last dose of study drug (Up to Week 133)
Primary	Number of Participants With Amyloid-Related Imaging Abnormalities-Haemosiderin Deposition (ARIA-H) AEs		Baseline [Day 1] up to 4 weeks after the last dose of study drug (Up to Week 133)
Primary	Number of Participants With Anti-drug Antibody (ADA) to Gantenerumab		Up to Week 133
Primary	Number of Participants With Injection-Site Reactions		Baseline [Day 1] up to 4 weeks after the last dose of study drug (Up to Week 133)
Primary	Number of Participants Who Discontinued Treatment Due to AEs	An AE was defined as any untoward medical occurrence in a participant administered with gantenerumab and which does not necessarily have a causal relationship with gantenerumab. SAE is any significant hazard, contraindication, side effect that is fatal or life threatening; requires in-patient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; is medically significant or requires intervention to prevent one or other of the outcomes listed above, and which does not necessarily have a causal relationship with gantenerumab.	Baseline [Day 1] up to 4 weeks after the last dose of study drug (Up to Week 133)