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Safety and Efficacy Study of Gantenerumab in Participants With Early Alzheimer's Disease (AD)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03443973
Recruitment Status : Recruiting
First Posted : February 23, 2018
Last Update Posted : March 16, 2020
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche

Study Description
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Brief Summary:
This randomized, double-blind, placebo-controlled, parallel group study will evaluate the efficacy and safety of gantenerumab versus placebo in participants with early (prodromal to mild) AD. All participants must show evidence of beta-amyloid pathology. Eligible participants will be randomized 1:1 to receive either subcutaneous (SC) injection of gantenerumab or placebo. The primary efficacy assessment will be performed at the end of the double blind period at week 104. Participants will then be offered to enter into an open-label extension (OLE). Participants not willing to go to the OLE will participate in a long term follow-up period for up to 50 weeks after the last gantenerumab dose.

Condition or disease Intervention/treatment Phase
Alzheimer Disease Drug: Gantenerumab Drug: Placebo Phase 3

Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 1016 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: A Phase III, Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Efficacy, and Safety Study of Gantenerumab in Patients With Early (Prodromal to Mild) Alzheimer's Disease
Actual Study Start Date : August 22, 2018
Estimated Primary Completion Date : May 31, 2022
Estimated Study Completion Date : May 3, 2023

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
Experimental: Gantenerumab
Gantenerumab will be administered as SC injections with gradual uptitration.
 Drug: Gantenerumab
Gantenerumab will be administered as per the schedule specified in the respective arm.
Other Name: RO4909832
Placebo Comparator: Placebo
Placebo will be administered as SC injections with gradual uptitration.
 Drug: Placebo
Placebo matching to gantenerumab will be administered as per the schedule specified in the respective arm.


Outcome Measures
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Primary Outcome Measures :
  1. Change From Baseline to Week 104 in Global Outcome, as Measured by Clinical Dementia Rating−Sum of Boxes (CDR-SOB) [ Time Frame: Baseline up to Week 104 ]

Secondary Outcome Measures :
  1. Change From Baseline to Week 104 in Mini-Mental State Examination (MMSE) Total Score [ Time Frame: Baseline up to Week 104 ]
  2. Change From Baseline to Week 104 in Alzheimer Disease Assessment Scale-Cognition Subscale 11 (ADAS-Cog11) Subscale Score [ Time Frame: Baseline up to Week 104 ]
  3. Change from Baseline to Week 104 in Alzheimer Disease Assessment Scale-Cognition, Subscale 13 (ADAS-Cog13) [ Time Frame: Baseline up to Week 104 ]
  4. Change From Baseline to Week 104 in Verbal Fluency Task Score [ Time Frame: Baseline up to Week 104 ]
  5. Change From Baseline to Week 104 in Coding [ Time Frame: Change from baseline to Week 104 in the Wechsler Adult Intelligence Scale - Fourth Edition (WAIS-IV) coding subtest. ]
  6. Change From Baseline to Week 104 in Functional Activities Questionnaire (FAQ) Score [ Time Frame: Baseline to Week 104 ]
  7. Change From Baseline to Week 104 in Alzheimer Disease Cooperative Study Group-Activities of Daily Living (ADCS-ADL) Total Score [ Time Frame: Baseline up to Week 104 ]
  8. Percentage of Participants With Adverse Events (AEs) [ Time Frame: Baseline up to end of study (week 152) or Week 35 (Open label extension) ]
  9. Change in Columbia-Suicide Severity Rating Scale (C-SSRS) Score [ Time Frame: Baseline up to Week 104 or Week 24 in Open label extension ]
  10. Percentage of Participants with Amyloid-Related Imaging Abnormalities-Edema (ARIA-E) Confirmed by Magnetic Resonance Imaging (MRI) [ Time Frame: Baseline up to end of study (week 152) or Week 35 (Open label extension) ]
  11. Percentage of Participants with Amyloid-Related Imaging Abnormalities-Haemosiderin deposition (ARIA-H) Confirmed by Magnetic Resonance Imaging (MRI) [ Time Frame: Baseline up to end of study (week 152) or Week 35 (Open label extension) ]
  12. Percentage of Participants with Injection-Site Reactions [ Time Frame: Baseline up to end of study (week 152) or Week 35 (Open label extension) ]
  13. Percentage of Participants With Anti-Drug Antibodies (ADA) to Gantenerumab [ Time Frame: Baseline up to end of study (week 152) or Week 35 (Open label extension) ]
  14. Plasma Concentration of Gantenerumab [ Time Frame: Baseline, Week 2, 24, 41, 52, 76, 103, 116, 152, and at early termination and unscheduled visit, Week 1 and Week 24 (Open label extension) ]
  15. Change from Baseline in Brain Amyloid Load as Measured by Amyloid Positron Emission Tomography (PET) Scan in a subset of patients up to Week 104 [ Time Frame: Baseline up to Week 104 ]
  16. Change From Baseline in Brain Tau Load, as Measured by Tau PET Scan in a Subset of Patients up to Week 104 [ Time Frame: Baseline up to Week 104 ]
  17. Change From Baseline in Cerebral Spinal Fluid (CSF) Marker of Disease in a Subset of Patients - Amyloid-beta 1−42 (Aβ1−42) up to Week 104 [ Time Frame: Baseline up to Week 104 ]
  18. Change From Baseline in CSF Marker of Disease in a Subset of Patients - Total Tau up to Week 104 [ Time Frame: Baseline up to Week 104 ]
  19. Change From Baseline in CSF Marker of Disease in a Subset of Patients - Phosphorylated Tau up to Week 104 [ Time Frame: Baseline up to Week 104 ]
  20. Change From Baseline in Volumetric Magnetic Resonance Imaging (MRI) up to Week 104 [ Time Frame: Baseline up to Week 104 ]
    MRI will be used to assess the effect of treatment on volume of whole brain, ventricles, hippocampus, or other structures.


Eligibility Criteria
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Ages Eligible for Study:   50 Years to 90 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Key Inclusion criteria:

  • Meets National Institute on Aging/Alzheimer's Association (NIAAA) core clinical criteria for probable AD dementia or prodromal AD (consistent with the NIAAA diagnostic criteria and guidelines for mild cognitive impairment)
  • Evidence of the AD pathological process, as confirmed by CSF tau/A-beta42or amyloid PET scan
  • Demonstrated abnormal memory function
  • MMSE score greater than or equal to 22 (≥ 22)
  • Clinical dementia rating-global score (CDR-GS) of 0.5 or 1.0
  • Availability of a reliable study partner who accepts to participate in study procedures throughout the 2 years duration of study
  • If receiving symptomatic AD medications, the dosing regimen must have been stable for 3 months prior to screening and until randomization
  • For enrollment in the China extension, patients must have residence in mainland China, Hong Kong, or Taiwan and be of Chinese ancestry
  • For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods

Key Exclusion criteria:

  • Any evidence of a condition other than AD that may affect cognition
  • History of schizophrenia, schizoaffective disorder, major depression, or bipolar disorder
  • 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 (e.g., glioma, meningioma) 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
  • At risk for suicide in the opinion of the investigator
  • Alcohol and/or substance abuse or dependants in past 2 years
  • Relevant brain hemorrhage, bleeding disorder and cerebrovascular abnormalities
  • Any contraindications to brain MRI
  • Unstable or clinically significant cardiovascular, kidney or liver disease
  • Uncontrolled hypertension
  • Unstable or clinically significant cardiovascular disease
  • Abnormal thyroid function
  • Patients with evidence of folic acid deficiency

Exclusion for Open-Label Extension (OLE):

  • Discontinued from study treatment during the double-blind treatment period
  • Received any other investigational medication during the double-blind treatment period or after the end of double-blind treatment
  • Participation in the OLE deemed inappropriate by the investigator
  • Presence of ARIA-E findings at the Week 104 MRI scan
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03443973


Contacts
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Contact: Reference Study ID Number: WN39658 www.roche.com/about_roche/roche_worldwide.htm 888-662-6728 (U.S. and Canada) global-roche-genentech-trials@gene.com

Locations
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Sponsors and Collaborators
Hoffmann-La Roche
Investigators
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Study Director: Clinical Trials Hoffmann-La Roche
More Information
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Additional Information:
US residents may click here to find out more about participation in this study  This link exits the ClinicalTrials.gov site

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Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT03443973    
Other Study ID Numbers: WN39658
2017-001365-24 ( EudraCT Number )
First Posted: February 23, 2018    Key Record Dates
Last Update Posted: March 16, 2020
Last Verified: March 2020
Individual Participant Data (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.clinicalstudydatarequest.com). Further details on Roche's criteria for eligible studies are available here (https://clinicalstudydatarequest.com/Study-Sponsors/Study-Sponsors-Roche.aspx). 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).

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Alzheimer Disease
Dementia
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
 Tauopathies
Neurodegenerative Diseases
Neurocognitive Disorders
Mental Disorders