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

NCT04339413 | Terminated Phase 3 Results FDA Drug

• 1 other identifier: WN41874
• Study Type: interventional
• Target: 116
• Locations: 17 countries
• Sites: 56

Brief 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.

Conditions

Alzheimer Disease

Outcome Measures

Primary Outcomes (7)

• 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)

• 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

• 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)

• 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)

• Number of Participants With Anti-drug Antibody (ADA) to Gantenerumab

  Up to Week 133

• 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)

• 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)

Study Arms (2)

SCarlet RoAD

EXPERIMENTAL

Participants enrolled from the open label extension (OLE) part of parent study WN25203, received gantenerumab, up to 1200 milligram (mg), subcutaneous (SC) injection, every 4 weeks (Q4W) for up to 129 weeks.

Drug: Gantenerumab

Marguerite RoAD

EXPERIMENTAL

Participants enrolled from the OLE part of parent study WN28745, received gantenerumab, up to 1200 mg, SC injection, Q4W for up to 129 weeks.

Drug: Gantenerumab

Interventions

Gantenerumab DRUG

Gantenerumab was administered as SC injection Q4W.

Marguerite RoAD; SCarlet RoAD

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (56)

Banner Sun Health Research Insitute

Sun City, Arizona, 85351, United States

Location

California Neuroscience Research Medical Group, Inc

Sherman Oaks, California, 91403, United States

Location

Accelerated Enrollment Solutions

Orlando, Florida, 32806, United States

Location

University of South Florida

Tampa, Florida, 33612, United States

Location

Bioclinica The Villages

The Villages, Florida, 32162, United States

Location

Western Michigan University Homer Stryker M.D. School of Medicine Center for Clinical Research

Kalamazoo, Michigan, 49008, United States

Location

Richmond Behavioral Associates

Staten Island, New York, 10314, United States

Location

Alzheimer's Memory Center

Matthews, North Carolina, 28105, United States

Location

Central States Research

Tulsa, Oklahoma, 74136, United States

Location

Neurology Clinic PC

Cordova, Tennessee, 38018, United States

Location

Senior Adults Specialty Research

Austin, Texas, 78757, United States

Location

Instituto Neurologia Bs As

Ciudad Autonoma Buenos Aires, C1426ANZ, Argentina

Location

The Queen Elizabeth Hospital; Neurology

Woodville, South Australia, 5011, Australia

Location

Heidelberg Repatriation Hospital; Medical and Cognitive Research Centre

Heidelberg West, Victoria, 3081, Australia

Location

Centricity Research

Halifax, Nova Scotia, B3S 1N2, Canada

Location

True North Clinical Research-Halifax

Halifax, Nova Scotia, B3S 1N2, Canada

Location

Kawartha Centre - Redefining Healthy Aging

Peterborough, Ontario, K9H 2P4, Canada

Location

Toronto Memory Program

Toronto, Ontario, M3B 2S7, Canada

Location

Alpha Recherche Clinique

Québec, G3K 2P8, Canada

Location

Especialidades Medicas LYS

Santiago, 7560356, Chile

Location

Rigshospitalet, Hukommelsesklinikken

København Ø, 2100, Denmark

Location

Nuovo Ospedale Civile S. Agostino-Estense; Clinica Neurologica ? Dipartimento di Neuroscienze

Modena, Emilia-Romagna, 41126, Italy

Location

Azienda Ospedaliera Spedali Civili; Scienze Neurologiche

Brescia, Lombardy, 25100, Italy

Location

IRCCS ?Centro S. Giovanni di Dio? Fatebenefratelli -UO Alzheimer

Brescia, Lombardy, 25125, Italy

Location

Irccs Multimedica Santa Maria; Unita' Di Neurologia

Castellanza, Lombardy, 21053, Italy

Location

Fondazione San Raffaele Del Monte Tabor; Dipartimento Di Neurologia

Milan, Lombardy, 20132, Italy

Location

Medical Corporation Hakuyokai Kashiwado Hospital

Chiba, 260-8656, Japan

Location

Juntendo University Urayasu Hospital; Neurology

Chiba, 279-0021, Japan

Location

National Hospital Organization Hiroshima-Nishi Medical Center

Hiroshima, 739-0696, Japan

Location

Hospital Mexico Americano

Guadalajara, Mexico CITY (federal District), 44610, Mexico

Location

Hospital Universitario; Dr. Jose E. Gonzalez

Monterrey, Nuevo León, 64460, Mexico

Location

AVIX Investigación Clínica S.C

Monterrey, Nuevo León, 64710, Mexico

Location

Brain Research Center B.V

Amsterdam, 1081 GN, Netherlands

Location

NZOZ NEURO-KARD Ilkowski i Partnerzy Sp. Partn. Lek

Późna, 61-853, Poland

Location

Przychodnia Specjalistyczna PROSEN

Warsaw, 01-231, Poland

Location

Centrum Medyczne NeuroProtect

Warsaw, 01-684, Poland

Location

Saint Petersburg State Institution of Healthcare City Geriatric Medico-Social Center

Saint Petersburg, Sankt-Peterburg, 190103, Russia

Location

FSMEI HPE ?Military Medical Academy n.a. S.M.Kirov"of Minist

Saint Petersburg, Sankt-Peterburg, 194044, Russia

Location

Inha University Hospital

Incheon, 22332, South Korea

Location

Seoul St Mary's Hospital

Seoul, 06591, South Korea

Location

Ewha Womans University Hospital (Seoul)

Seoul, 07804, South Korea

Location

Hospital General Universitario de Elche; Servicio de Neurología

Elche, Alicante, 03203, Spain

Location

Hospital Mutua De Terrasa; Servicio de Neurologia

Terrassa, Barcelona, 08222, Spain

Location

Hospital del Mar; Servicio de Neurologia

Barcelona, 08003, Spain

Location

Fundación ACE; Servicio de Neurología

Barcelona, 08028, Spain

Location

Hospital Universitario 12 de Octubre; Servicio de Neurologia

Madrid, 28041, Spain

Location

Hospital Universitario Dr. Peset; Servicio de Neurologia

Valencia, 46017, Spain

Location

Hospital Universitario la Fe; Servicio de Neurologia

Valencia, 46026, Spain

Location

Felix Platter-Spital Medizin Geriatrie

Basel, 4002, Switzerland

Location

Istanbul University Istanbul School of Medicine; Neurology

Istanbul, 34093, Turkey (Türkiye)

Location

Dokuz Eylul University Medicine Faculty; Noroloji Departmani

Izmir, 35340, Turkey (Türkiye)

Location

Ondokuz Mayis University School of Medicine; Neurology

Samsun, 55139, Turkey (Türkiye)

Location

Llandough Hospital; Llandough Hospital Memory Team 3rd Floor Academic Building

Cardiff, CF64 2XX, United Kingdom

Location

Imperial Memory Unit, Charing Cross Hospital; Level 10 West, Department of Neurosciences

London, W6 8RF, United Kingdom

Location

Campus for Ageing & Vitality; Clincal Ageing Research Unit

Newcastle, NE4 5PL, United Kingdom

Location

Hollins Park Hospital

Warrington, WA2 8WA, United Kingdom

Location

MeSH Terms

Conditions

Alzheimer Disease

Interventions

gantenerumab

Condition Hierarchy (Ancestors)

Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders

Results Point of Contact

• Title: Medical Communications
• Organization: Hoffmann-La Roche

genentech@druginfo.com

800-821-8590

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 7, 2020
• First Posted: April 9, 2020
• Study Start: May 22, 2020
• Primary Completion: January 4, 2023
• Study Completion: January 4, 2023
• Last Updated: January 18, 2024
• Results First Posted: January 18, 2024

Record last verified: 2023-12

Data Sharing

• IPD Sharing: Will share

Locations

ES (7); CA (5); DK (1); TU (3); GB (4); IT (5); US (11); JP (3); PL (3); CL (1); ME (3); AU (2); RU (2); CH (1); AR (1); KR (3); NL (1)