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
Overview
- Phase
- Phase 3
- Intervention
- Gantenerumab
- Conditions
- Alzheimer Disease
- Sponsor
- Hoffmann-La Roche
- Enrollment
- 1053
- Locations
- 172
- Primary Endpoint
- DBT Period: Change From Baseline to Week 116 in Global Outcome, as Measured by CDR-SB
- Status
- Terminated
- Last Updated
- 2 years ago
Overview
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- Not provided
Exclusion Criteria
- Not provided
Arms & Interventions
Gantenerumab
Gantenerumab will be administered as SC injections with gradual uptitration.
Intervention: Gantenerumab
Placebo
Placebo will be administered as SC injections with gradual uptitration.
Intervention: Placebo
Outcomes
Primary Outcomes
DBT Period: Change From Baseline to Week 116 in Global Outcome, as Measured by CDR-SB
Time Frame: Baseline, Week 116
CDR was derived through semi-structured interview with the participant and an appropriate informant, and it rated impairment across six domains: memory, orientation, judgment, and problem solving, community affairs, home and hobbies, and personal care on a 5-point scale for which 0=no impairment, 0.5=questionable impairment, and 1, 2, and 3=mild, moderate, and severe impairment, respectively. The CDR-SB is based on summing each of the domain box scores with total score ranging from 0-18 with higher scores reflecting greater cognitive and functional impairment. A negative change from baseline indicates improvement.
China Extension: DBT Period: Change From Baseline to Week 116 in Global Outcome, as Measured by CDR-SB
Time Frame: Baseline, Week 116
CDR was derived through semi-structured interview with the participant and an appropriate informant, and it rated impairment across six domains: memory, orientation, judgment, and problem solving, community affairs, home and hobbies, and personal care on a 5-point scale for which 0=no impairment, 0.5=questionable impairment, and 1, 2, and 3=mild, moderate, and severe impairment, respectively. The CDR-SB is based on summing each of the domain box scores with total score ranging from 0-18 with higher scores reflecting greater cognitive and functional impairment. A negative change from baseline indicates improvement.
Secondary Outcomes
- DBT Period: Change From Baseline to Week 116 in Verbal Fluency Task (VFT) Score(Baseline, Week 116)
- DBT Period: Change From Baseline to Week 116 in the Coding (Digit Symbol Substitution Test [DSST]) Subtest(Baseline, Week 116)
- DBT Period: Change From Baseline to Week 116 in Alzheimer's Disease Cooperative Study-Instrumental Activities of Daily Living (ADCS-iADL) Instrumental Score(Baseline, Week 116)
- DBT Period: Number of Participants With at Least One Adverse Event (AE)(From Day 1 up to 14 weeks after the last dose of blinded study drug (up to 131 weeks))
- DBT Period: Change From Baseline to Week 116 in Alzheimer Disease Assessment Scale-Cognition Subscale 13 (ADAS-Cog13) Score(Baseline, Week 116)
- DBT Period: Change From Baseline to Week 116 in Alzheimer's Disease Cooperative Study- Activities of Daily Living (ADCS-ADL) Total Score(Baseline, Week 116)
- DBT Period: Change From Baseline to Week 116 in Functional Activities Questionnaire (FAQ) Score(Baseline, Week 116)
- DBT Period: Change From Baseline to Week 116 in Mini-Mental State Examination (MMSE) Total Score(Baseline, Week 116)
- DBT Period: Change From Baseline to Week 116 in Alzheimer Disease Assessment Scale-Cognition Subscale 11 (ADAS-Cog11) Score(Baseline, Week 116)
- DBT Period: Number of Participants With Post-baseline Suicidal Ideation or Suicidal Behavior as Measured Using Columbia-Suicide Severity Rating Scale (C-SSRS)(From Day 1 up to 14 weeks after the last dose of blinded study drug (up to 131 weeks))
- DBT Period: Number of Participants With at Least One Amyloid-Related Imaging Abnormalities-Edema (ARIA-E) Magnetic Resonance Imaging (MRI) Finding(From Day 1 up to 14 weeks after the last dose of blinded study drug (up to 131 weeks))
- DBT Period: Number of Participants With at Least One Amyloid-Related Imaging Abnormalities-Haemosiderin Deposition (ARIA-H) MRI Finding(From Day 1 up to 14 weeks after the last dose of blinded study drug (up to 131 weeks))
- DBT Period: Number of Participants With Injection-Site Reactions(From Day 1 up to 14 weeks after the last dose of blinded study drug (up to 131 weeks))
- DBT Period: Number of Participants With Anti-Drug Antibodies (ADA) to Gantenerumab(From Day 1 up to 14 weeks after the last dose of blinded study drug (up to 131 weeks))
- DBT Period: Change From Baseline to Week 116 in Brain Amyloid Load as Measured by Amyloid Positron Emission Tomography (PET) Scan in a Subset of Participants(Baseline, Week 116)
- DBT Period: Change From Baseline to Week 116 in Brain Tau Load, as Measured by Tau PET Scan in a Subset of Participants(Baseline, Week 116)
- DBT Period: Percent Change From Baseline to Week 116 in Cerebrospinal Fluid (CSF) Marker of Disease in a Subset of Participants - Total Tau (tTau)(Baseline, Week 116)
- DBT Period: Percent Change From Baseline to Week 116 in CSF Marker of Disease in a Subset of Participants - Phosphorylated Tau (pTau-181)(Baseline, Week 116)
- DBT Period: Percent Change From Baseline to Week 116 in CSF Marker of Disease in a Subset of Participants - Neurofilament Light Chain (NFL)(Baseline, Week 116)
- DBT Period: Percent Change From Baseline to Week 116 in CSF Marker of Disease in a Subset of Participants - Neurogranin(Baseline, Week 116)
- China - DBT Period: Change From Baseline to Week 116 in ADAS-Cog13 Score(Baseline, Week 116)
- China - DBT Period: Change From Baseline to Week 116 in ADCS-ADL Total Score(Baseline, Week 116)
- China - DBT Period: Change From Baseline to Week 116 in FAQ Score(Baseline, Week 116)
- China - DBT Period: Change From Baseline to Week 116 in the Coding (DSST) Subtest(Baseline, Week 116)
- China - DBT Period: Number of Participants With at Least One AE(From Day 1 up to 14 weeks after the last dose of blinded study drug (up to 124 weeks))
- China - DBT Period: DBT Period: Change From Baseline to Week 116 in MMSE Total Score(Baseline, Week 116)
- China - DBT Period: Change From Baseline to Week 116 in ADAS-Cog11 Score(Baseline, Week 116)
- China - DBT Period: Change From Baseline to Week 116 in VFT Score(Baseline, Week 116)
- China - DBT Period: Number of Participants With Post-baseline Suicidal Ideation or Suicidal Behavior as Measured Using C-SSRS(From Day 1 up to 14 weeks after the last dose of blinded study drug (up to 124 weeks))
- China - DBT Period: Number of Participants With at Least One ARIA-E MRI Finding(From Day 1 up to 14 weeks after the last dose of blinded study drug (up to 124 weeks))
- China - DBT Period: Number of Participants With at Least One ARIA-H MRI Finding(From Day 1 up to 14 weeks after the last dose of blinded study drug (up to 124 weeks))
- China - DBT Period: Number of Participants With Injection-Site Reactions(From Day 1 up to 14 weeks after the last dose of blinded study drug (up to 124 weeks))
- OLE Period: Number of Participants With at Least One AEs(From day of first dose in OLE period up to 14 weeks after the last OLE dose (up to 68 weeks))
- OLE Period: Number of Participants With Post-baseline Suicidal Ideation or Suicidal Behavior as Measured Using C-SSRS(From day of first dose in OLE period up to 14 weeks after the last OLE dose (up to 68 weeks))
- OLE Period: Number of Participants With at Least One ARIA-H MRI Finding(From day of first dose in OLE period up to 14 weeks after the last OLE dose (up to 68 weeks))
- OLE Period: Number of Participants With at Least One ARIA-E MRI Finding(From day of first dose in OLE period up to 14 weeks after the last OLE dose (up to 68 weeks))