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

• ClinicalTrials.gov Identifier: NCT04592341
• Recruitment Status: Active, not recruiting
• First Posted: October 19, 2020
• Last Update Posted: April 15, 2022
• Sponsor: Hoffmann-La Roche
• Information provided by (Responsible Party): Hoffmann-La Roche

Tracking Information

• First Submitted Date: October 2, 2020
• First Posted Date: October 19, 2020
• Last Update Posted Date: April 15, 2022
• Actual Study Start Date: November 18, 2020
• Estimated Primary Completion Date: July 27, 2023 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: October 14, 2020): Change from Baseline in Deposited Amyloid as Measured by Brain Amyloid PET Centiloid (CL) Levels [ Time Frame: Up to Week 104 ]
• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: October 14, 2020)

• Responses to home administration questionnaire [ Time Frame: Up to Week 104 ]
  The home administration questionnaire will capture confidence, ease of use, convenience, and overall satisfaction.
• Percentage of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs) [ Time Frame: Up to Week 104 ]
• Change in the Columbia-Suicide Severity Rating Scale (C-SSRS) Score [ Time Frame: Up to Week 104 ]
• Percentage of Participants with Amyloid-Related Imaging Abnormalities-Edema (ARIA-E) Confirmed by Magnetic Resonance Imaging (MRI) [ Time Frame: Up to Week 104 ]
• Percentage of Participants with Amyloid-Related Imaging Abnormalities-Haemosiderin deposition (ARIA-H) Confirmed by Magnetic Resonance Imaging (MRI) [ Time Frame: Up to Week 104 ]
• Percentage of Participants with Injection-Site Reactions (IRS) [ Time Frame: 24 hours after study drug administration, up to Week 104 ]
  Injection reactions (local and systemic) are defined as adverse events that occur during or within 24 hours after study drug administration that are judged to be related to the study drug injection.
• Percentage of Participants with Anti-Drug Antibodies to Gantenerumab [ Time Frame: Up to Week 104 ]
• Plasma Concentration of SC Gantenerumab at specified timepoints [ Time Frame: Up to Week 104 ]
• Change in Brain Amyloid Based on Different Dosing Frequency [ Time Frame: Up to Week 104 ]

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Study to Evaluate the Pharmacodynamic (PD) Effects of Once Weekly Administration of Gantenerumab in Participants With Early Alzheimer's Disease (AD)
• Official Title: A Phase II, Multicenter, Open-Label, Single Arm Study to Evaluate the Pharmacodynamic Effects of Once Weekly Administration of Gantenerumab in Participants With Early (Prodromal to Mild) Alzheimer's Disease
• 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 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: N/A; Intervention Model: Sequential Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Alzheimer Disease

Intervention

Drug: 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.

Study Arms

Experimental: 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.

Intervention: Drug: Gantenerumab

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: April 14, 2022): 193
• Original Estimated Enrollment (submitted: October 14, 2020): 150
• Estimated Study Completion Date: November 16, 2023
• Estimated Primary Completion Date: July 27, 2023 (Final data collection date for primary outcome measure)

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 50 Years to 90 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Belgium, France, Germany, Italy, Poland, Spain, United Kingdom, United States

Administrative Information

• NCT Number: NCT04592341
• Other Study ID Numbers: WN29722; 2020-001384-87 ( Registry Identifier: EudraCT )
• Has Data Monitoring Committee: Not Provided

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Yes
• Plan Description: Qualified researchers may request access to individual patient level data through the clinical study data request platform (www.vivli.org). Further details on Roche's criteria for eligible studies are available here (https://vivli.org/ourmember/roche/). For further details on Roche's Global Policy on the Sharing of Clinical Information and how to request access to related clinical study documents, see here (https://www.roche.com/research_and_development/who_we_are_how_we_work/clinical_trials/our_commitment_to_data_sharing.htm).
• Supporting Materials: Study Protocol

• Responsible Party: Hoffmann-La Roche
• Study Sponsor: Hoffmann-La Roche
• Collaborators: Not Provided

Investigators

• Study Director: Clinical Trials; Hoffmann-La Roche

• PRS Account: Hoffmann-La Roche
• Verification Date: April 2022