Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu

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 : August 22, 2019
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 August 22, 2019
Actual Study Start Date  ICMJE August 22, 2018
Estimated Primary Completion Date May 31, 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 24, 2018)
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 ]
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 Complete list of historical versions of study NCT03443973 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: July 5, 2018)
  • 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 ]
  • 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, Subscale 13 (ADAS-Cog13) [ 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 Coding [ Time Frame: Change from baseline to Week 104 in the Wechsler Adult Intelligence Scale - Fourth Edition (WAIS-IV) coding subtest. ]
  • 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, 152, early termination visit ]
  • 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 ]
  • 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 ]
  • 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 ]
  • 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 ]
  • 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 ]
  • 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.
  • Change from Baseline to Week 104 in Instrumental Score [ Time Frame: Baseline Up to Week 104 ]
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 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.
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's 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: April 16, 2018)
760
Original Estimated Enrollment  ICMJE
 (submitted: February 19, 2018)
750
Estimated Study Completion Date  ICMJE May 2, 2023
Estimated Primary Completion Date May 31, 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 [MCI])
  • Evidence of the AD pathological process, as confirmed by CSF or amyloid PET scan
  • Demonstrated abnormal memory function
  • MMSE score great 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 baseline 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.

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
  • At risk for suicide in the opinion of the investigator
  • Patients with evidence of folic acid deficiency
  • 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
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 Not Provided
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 August 2019

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