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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 : June 17, 2020
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche

Tracking Information
First Submitted Date  ICMJE February 19, 2018
First Posted Date  ICMJE February 23, 2018
Last Update Posted Date June 17, 2020
Actual Study Start Date  ICMJE August 22, 2018
Estimated Primary Completion Date September 30, 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 15, 2020)
Change From Baseline to Week 116 in Global Outcome, as Measured by Clinical Dementia Rating−Sum of Boxes (CDR-SOB) [ Time Frame: Baseline up to Week 116 ]
Original Primary Outcome Measures  ICMJE
 (submitted: February 19, 2018)
Change From Baseline to Week 104 in Clinical Dementia Rating-Sum of Boxes (CDR-SOB) Score [ Time Frame: Baseline up to Week 104 ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: June 15, 2020)
  • Change From Baseline to Week 116 in Mini-Mental State Examination (MMSE) Total Score [ Time Frame: Baseline up to Week 116 ]
  • Change From Baseline to Week 116 in Alzheimer Disease Assessment Scale-Cognition Subscale 11 (ADAS-Cog11) Subscale Score [ Time Frame: Baseline up to Week 116 ]
  • Change from Baseline to Week 116 in Alzheimer Disease Assessment Scale-Cognition, Subscale 13 (ADAS-Cog13) [ Time Frame: Baseline up to Week 116 ]
  • Change From Baseline to Week 116 in Verbal Fluency Task Score [ Time Frame: Baseline up to Week 116 ]
  • Change From Baseline to Week 116 in Coding [ Time Frame: Change from baseline to Week 116 in the Wechsler Adult Intelligence Scale - Fourth Edition (WAIS-IV) coding subtest. ]
  • Change From Baseline to Week 116 in Functional Activities Questionnaire (FAQ) Score [ Time Frame: Baseline to Week 116 ]
  • Change From Baseline to Week 116 in Alzheimer Disease Cooperative Study Group-Activities of Daily Living (ADCS-ADL) Total Score [ Time Frame: Baseline up to Week 116 ]
  • Percentage of Participants With Adverse Events (AEs) [ Time Frame: Baseline up to end of study (week 164) or Week 35 (Open label extension) ]
  • Change in Columbia-Suicide Severity Rating Scale (C-SSRS) Score [ Time Frame: Baseline up to Week 116 or Week 24 in Open label extension ]
  • 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 164) or Week 35 (Open label extension) ]
  • 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 164) or Week 35 (Open label extension) ]
  • Percentage of Participants with Injection-Site Reactions [ Time Frame: Baseline up to end of study (week 164) or Week 35 (Open label extension) ]
  • Percentage of Participants With Anti-Drug Antibodies (ADA) to Gantenerumab [ Time Frame: Baseline up to end of study (week 164) or Week 35 (Open label extension) ]
  • Plasma Concentration of Gantenerumab [ Time Frame: Baseline, Week 2, 24, 41, 52, 76, 103, 115, 128, 164, and at early termination and unscheduled visit, Week 1 and Week 24 (Open label extension) ]
  • Change from Baseline in Brain Amyloid Load as Measured by Amyloid Positron Emission Tomography (PET) Scan in a subset of patients up to Week 116 [ Time Frame: Baseline up to Week 116 ]
  • Change From Baseline in Brain Tau Load, as Measured by Tau PET Scan in a Subset of Patients up to Week 116 [ Time Frame: Baseline up to Week 116 ]
  • 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 116 [ Time Frame: Baseline up to Week 116 ]
  • Change From Baseline in CSF Marker of Disease in a Subset of Patients - Total Tau up to Week 116 [ Time Frame: Baseline up to Week 116 ]
  • Change From Baseline in CSF Marker of Disease in a Subset of Patients - Phosphorylated Tau up to Week 116 [ Time Frame: Baseline up to Week 116 ]
  • Change From Baseline in Volumetric Magnetic Resonance Imaging (MRI) up to Week 116 [ Time Frame: Baseline up to Week 116 ]
    MRI will be used to assess the effect of treatment on volume of whole brain, ventricles, hippocampus, or other structures.
Original Secondary Outcome Measures  ICMJE
 (submitted: February 19, 2018)
  • Change From Baseline to Week 104 in Alzheimer Disease Assessment Scale-Cognition 11 (ADAS-Cog11) Subscale Score [ Time Frame: Baseline up to Week 104 ]
  • Change From Baseline to Week 104 in Mini-Mental State Examination (MMSE) Total Score [ Time Frame: Baseline up to Week 104 ]
  • Change From Baseline to Week 104 in Alzheimer Disease Assessment Scale-Cognition 13 (ADAS-Cog13) Subscale Score [ Time Frame: Baseline up to Week 104 ]
  • Change From Baseline to Week 104 in Verbal Fluency Task Score [ Time Frame: Baseline up to Week 104 ]
  • Change From Baseline to Week 104 in Functional Activities Questionnaire (FAQ) Score [ Time Frame: Baseline to Week 104 ]
  • 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 ]
  • Percentage of Participants With Adverse Events (AEs) [ Time Frame: Baseline up to end of study (up to Week 152) ]
  • Percentage of Participants With Anti-Drug Antibodies (ADA) to Gantenerumab [ Time Frame: Baseline up to end of study (up to Week 152) ]
  • Plasma Concentration of Gantenerumab [ Time Frame: Pre-dose (0 hour [hr]) at Baseline (Day 1), Weeks 24, 52, 76; and at Weeks 2, 41, 103, 116, early termination visit (up to Week 152) ]
  • Change From Baseline in Brain Amyloid Load, as Measured by Amyloid Positron Emission Tomography (PET) Scan up to Week 104 [ Time Frame: Baseline up to Week 104 ]
  • Change From Baseline in Brain Tau Load, as Measured by Tau PET Scan up to Week 104 [ Time Frame: Baseline up to Week 104 ]
  • Change From Baseline in Cerebral Spinal Fluid (CSF) Marker of Disease - Amyloid-beta 1−42 (Aβ1−42) up to Week 104 [ Time Frame: Baseline up to Week 104 ]
  • Change From Baseline in CSF Marker of Disease - Total Tau up to Week 104 [ Time Frame: Baseline up to Week 104 ]
  • Change From Baseline in CSF Marker of Disease - Phosphorylated Tau up to Week 104 [ Time Frame: Baseline up to Week 104 ]
  • 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.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Safety and Efficacy Study of Gantenerumab in Participants With Early Alzheimer's Disease (AD)
Official Title  ICMJE 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
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 116. 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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Condition  ICMJE Alzheimer Disease
Intervention  ICMJE
  • Drug: Gantenerumab
    Gantenerumab will be administered as per the schedule specified in the respective arm.
    Other Name: RO4909832
  • Drug: Placebo
    Placebo matching to gantenerumab will be administered as per the schedule specified in the respective arm.
Study Arms  ICMJE
  • Experimental: Gantenerumab
    Gantenerumab will be administered as SC injections with gradual uptitration.
    Intervention: Drug: Gantenerumab
  • Placebo Comparator: Placebo
    Placebo will be administered as SC injections with gradual uptitration.
    Intervention: Drug: Placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: March 12, 2020)
1016
Original Estimated Enrollment  ICMJE
 (submitted: February 19, 2018)
750
Estimated Study Completion Date  ICMJE November 3, 2023
Estimated Primary Completion Date September 30, 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 50 Years to 90 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
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
Listed Location Countries  ICMJE Argentina,   Belgium,   Chile,   Croatia,   Denmark,   Finland,   Japan,   Korea, Republic of,   Mexico,   Netherlands,   Poland,   Portugal,   Puerto Rico,   Singapore,   Spain,   Sweden,   Turkey,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03443973
Other Study ID Numbers  ICMJE WN39658
2017-001365-24 ( EudraCT Number )
Has Data Monitoring Committee Yes
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  ICMJE
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).
Responsible Party Hoffmann-La Roche
Study Sponsor  ICMJE Hoffmann-La Roche
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Clinical Trials Hoffmann-La Roche
PRS Account Hoffmann-La Roche
Verification Date June 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP