A Study to Evaluate the Pharmacodynamic (PD) Effects of Once Weekly Administration of Gantenerumab in Participants With Early Alzheimer's Disease (AD)

NCT ID: NCT04592341

Last Updated: 2024-03-27

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 192 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-11-18
• Study Completion Date: 2023-03-15

Brief Summary

This is a Phase II, multicenter, open-label, single arm, PD study in participants with early (prodromal to mild) AD to evaluate the effect of a once weekly (Q1W) dosing regimen of gantenerumab on deposited amyloid as measured by change from baseline to Week 104 (primary) and Week 208 in brain amyloid positron emission tomography (PET). The administration of gantenerumab as a single injection of Q1W will be investigated in this study, to simplify the dosing regimen for participants.

Conditions

Alzheimer Disease

Study Design

• Allocation Method: NA
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Gantenerumab

Participants will receive gantenerumab by subcutaneous (SC) injection at a dose of 120 mg every 4 weeks (Q4W) for 12 weeks, followed by 255 mg Q4W for 12 weeks, and 255 mg every 2 weeks (Q2W) for another 12 weeks, followed by the target dose 255 mg once weekly (Q1W) for up to Week 103. Participants who complete Week 104 visit will be given an option to take part in 2-year extension of the study to receive gantenerumab 255 mg Q1W for up to Week 207.

Group Type: EXPERIMENTAL

Gantenerumab

Intervention Type: DRUG

Gantenerumab will be administered by SC injection at a dose of 120 mg Q4W for 12 weeks, followed by 255 mg Q4W for 12 weeks, and 255 mg Q2W for another 12 weeks, followed by the target dose 255 mg Q1W for up to Week 103 and an optional dose of 255 mg Q1W for up to Week 207.

Interventions

Gantenerumab

Gantenerumab will be administered by SC injection at a dose of 120 mg Q4W for 12 weeks, followed by 255 mg Q4W for 12 weeks, and 255 mg Q2W for another 12 weeks, followed by the target dose 255 mg Q1W for up to Week 103 and an optional dose of 255 mg Q1W for up to Week 207.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Probable Alzheimer's Disease (AD) dementia or prodromal AD.
• Availability of a reliable study partner (non-professional caregiver) who accepts to participate in study procedure throughout the study duration
• The participant should be capable of completing all aspects of study assessments including MRI, clinical genotyping, and PET imaging, either alone or with the help of the study partner (non-professional caregiver).
• Adequate visual and auditory acuitysufficient to perform the neuropsychological testing (eye glasses and hearing aids are permitted).
• Evidence of AD pathological process, as confirmed by amyloid PET scan by qualitative read by the core/central PET laboratory.
• Prodromal or mild symptomatology, as defined by a screening Mini-Mental State Examination (MMSE) score >/=22 and Clinical Dementia Rating global score (CDR-GS) of 0.5 or 1.0, as well as a clinical dementia rating (CDR) memory domain score >/=0.5.
• If the participant is receiving symptomatic AD medications, a stable dosing regimen for at least 3 months prior to screening and until start of study treatment.
• 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.
• Agreement not to participate in other research studies for the duration of this trial, unless these are related Roche-sponsored non-interventional studies.
• For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods hat result in a failure rate of < 1% per year during the treatment period and for at least 16 weeks after the final dose of study drug.

Exclusion Criteria

• Any evidence of a condition other than AD that may affect cognition.
• History or presence of clinically evident systemic vascular disease that in the opinion of the investigator has the potential to affect cognitive function.
• History or presence of clinically evident cerebrovascular disease.
• History or presence of posterior reversible encephalopathy syndrome.
• History or presence of any stroke with clinical symptoms within the past 12 months, or documented history within the last 6 months of an acute event that is consistent with a transient ischemic attack.
• History of severe, clinically significant CNS trauma.
• History or presence of intracranial mass that could potentially impair cognition.
• Presence of infections that affect brain function or history of infections that resulted in neurologic sequelae.
• History or presence of systemic autoimmune disorders that potentially cause progressive neurologic disease with associated cognitive deficits.
• History of schizophrenia, schizoaffective disorder, major depression, or bipolar disorder.
• At risk for suicide in the opinion of the investigator.
• Alcohol and/or substance abuse or dependants in past 2 years.

• Minimum Eligible Age: 50 Years
• Maximum Eligible Age: 90 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Hoffmann-La Roche

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Clinical Trials

Role: STUDY_DIRECTOR

Hoffmann-La Roche

Locations

JEM Research LLC

Atlantis, Florida, United States

ClinCloud, LLC

Maitland, Florida, United States

Renstar Medical Research

Ocala, Florida, United States

Alzheimer?s Research and Treatment Center

Wellington, Florida, United States

Center for Advanced Research & Education

Gainesville, Georgia, United States

Summit Research Network Inc.

Portland, Oregon, United States

Abington Neurological Associates Willow Grove

Willow Grove, Pennsylvania, United States

Jessa Zkh (Campus Virga Jesse)

Hasselt, , Belgium

AZ Groeninge

Kortrijk, , Belgium

UZ Leuven Gasthuisberg

Leuven, , Belgium

Groupement Hospitalier Est - Hôpital Neurologique; Neurologie A (U502)

Bron, , France

CH Pitie Salpetriere; IM2A

Paris, , France

Gerontopole; Centre de Recherche clinique

Toulouse, , France

Ambulates Gesundheitszentrum der Charité GmbH; MVZ Neurologie Campus Benjamin Franklin

Berlin, , Germany

ECRC Experimental and Clinical Research Center, Charité Campus Berlin Buch, Memory Clinic

Berlin, , Germany

Klinikum rechts der Isar der TU München; Klinik für Psychiatrie und Psychotherapie

München, , Germany

Ospedale Cardinale Panico; Dip.Ricerca Clinica in Neurologia ? UO Malattie Neurodegenerative

Tricase (LE), Apulia, Italy

Ospedale San Giovanni Calibita Fatebenefratell;Neurologia

Rome, Lazio, Italy

Fondazione San Raffaele Del Monte Tabor; Dipartimento Di Neurologia

Milan, Lombardy, Italy

NZOZ Vitamed

Bydgoszcz, , Poland

Indywidualna Praktyka Lekarska Prof. Dr Hab. N. Med. Konrad Rejdak.

Lublin, , Poland

Senior Sp. Z O.O. Poradnia Psychogeriatryczna

Sopot, , Poland

Centrum Medyczne Euromedis Sp. z o.o.

Szczecin, , Poland

Centrum Medyczne NeuroProtect

Warsaw, , Poland

NZOZ WCA

Wroc?aw, , Poland

Policlínica Guipuzcoa; Servicio de Neurología

Donostia / San Sebastian, Guipuzcoa, Spain

Hospital Quiron de Madrid; Servicio de Neurologia

Pozuelo de Alarcón, Madrid, Spain

Hospital Universitario de la Princesa; Servicio de Neurologia

Madrid, , Spain

Hospital Universitario 12 de Octubre; Servicio de Neurologia

Madrid, , Spain

Hospital Universitari i Politecnic La Fe; Servicio de Neurología

Valencia, , Spain

Re-Cognition

Birmingham, , United Kingdom

Fritchie Centre

Cheltenham, , United Kingdom

Ninewells Hospital

Dundee, , United Kingdom

Charing Cross Hospital; Imperial Memory Unit, Level 10 West

London, , United Kingdom

Countries

United States; Belgium; France; Germany; Italy; Poland; Spain; United Kingdom

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2020-001384-87

Identifier Type: REGISTRY

Identifier Source: secondary_id

WN29722

Identifier Type: -

Identifier Source: org_study_id