Phase 3
N=797
A Study of Gantenerumab in Participants With Prodromal Alzheimer's Disease
Alzheimer's Disease
Bottom Line
View on ClinicalTrials.gov: NCT01224106 ↗Enrolled (actual)
797
Serious AEs
20.5%
Results posted
Dec 2021
Primary outcome: Primary: Mean Change From Baseline in Clinical Dementia Rating Scale Sum of Boxes (CDR-SOB) Total Score at Week 104 (Double-Blind Treatment Phase) — 1.19; 1.41; 1.47 Scores on a Scale — p=0.6744
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 3
- Interventions
- Gantenerumab (Drug); Placebo (Drug)
- Age
- Adult, Older Adult · 50+ yrs
- Sex
- All
- Sponsor
- Hoffmann-La Roche
- Primary completion
- Sep 2020
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Mean Change From Baseline in Clinical Dementia Rating Scale Sum of Boxes (CDR-SOB) Total Score at Week 104 (Double-Blind Treatment Phase) |
1.19; 1.41; 1.47 | 0.6744 |
| PRIMARY Number of Participants With Adverse Events (AEs) or Serious Adverse Events (SAEs) (OLE Phase) |
46; 100; 18; 28 | — |
| SECONDARY Mean Change From Baseline in Alzheimer Disease Assessment Scale-Cognitive Subscale 11 (ADAS-Cog-11) Scores at Week 104 (Double-Blind Treatment Phase) |
3.68; 3.52; 3.97 | 0.7458 |
| SECONDARY Time to Onset of Dementia at Week 104 (Double-Blind Treatment Phase) |
63.64; 62.98; 70.64 | — |
| SECONDARY Mean Change From Baseline in Cambridge Neuropsychological Test Automated Battery (CANTAB) Composite Score at Week 104 (Double-Blind Treatment Phase) |
-1.72; -1.37; -1.4; -1.93 | — |
| SECONDARY Mean Change From Baseline in Free and Cued Selective Reminding Test (FCSRT) Score at Week 104 (Double-Blind Treatment Phase) |
-4.05; -4.11; -6.42; -4.05 | — |
| SECONDARY Mean Change From Baseline in Functional Activities Questionnaire (FAQ) Score at Week 104 (Double-Blind Treatment Phase) |
3.59; 4.89; 4.03; 3.6 | 0.0825 |
| SECONDARY Mean Change From Baseline in CDR-Global Score at Week 104 (Double-Blind Treatment Phase) |
0.1; 0.18; 0.14; 0.1 | — |
| SECONDARY Mean Change From Baseline in Neuropsychiatric Inventory (NPI) Questionnaire Score at Week 104 (Double-Blind Treatment Phase) |
0.6; 0.39; 0.34; 0.72 | — |
| SECONDARY Percentage Change From Baseline in Cerebrospinal Fluid Biomarkers (Phosphorylated-tau [P-tau], Amyloid Beta 1-42 [Abeta 1-42], Total Tau [T-tau]) at Week 104 (Double-Blind Treatment Phase) |
2.77; -4.78; -7.34; 2.84; 3.43; -1.36 | 0.9734 |
| SECONDARY Percentage Change From Baseline in Hippocampal Volume at Week 104 (Double-Blind Treatment Phase) |
-7.61; -7.52; -7.34; -7.7; -7.8; -7.76 | — |
| SECONDARY Percentage Change From Baseline in Cortical Composite Sustained Uptake Volume Ratio (SUVr) in Different Brain Regions at Week 156 (Double-Blind Treatment Phase) |
6.26; 2.7; -8.36; 5.95; 5.41; 2.07 | — |
| SECONDARY Gantenerumab Plasma Concentrations at Different Time Points (Double-Blind Treatment Phase) |
3.56; 7.4; 2.87; 5.92; 3.7; 7.66 | — |
| SECONDARY Mean Change From Baseline in Mini Mental State Exam (MMSE) Score at Week 104 (Double-Blind Treatment Phase) |
-2.31; -2.46; -2.25 | — |
| SECONDARY Number of Participants With Adverse Events (AEs) or Serious Adverse Events (SAEs) (Double-Blind Treatment Phase) |
250; 241; 240; 55; 48; 46 | — |
| SECONDARY Percentage of Participants With Anti-Drug Antibodies (ADAs) (Double-Blind Treatment Phase) |
5.8; 7.5; 5.5; 5.0; 7.0; 6.4 | — |
| SECONDARY Mean Change From Baseline in Alzheimer Disease Assessment Scale-Cognitive Subscale 11 (ADAS-Cog-11) Scores at Week 156 (OLE Phase) |
5.8; 8.9 | — |
| SECONDARY Mean Change From Baseline in Clinical Dementia Rating Scale Sum of Boxes (CDR-SOB) Total Score at Week 156 (OLE Phase) |
3.3; 2.8 | — |
| SECONDARY Mean Change From Baseline in Alzheimer Disease Assessment Scale-Cognitive Subscale 13 (ADAS-Cog-13) Scores at Week 156 (OLE Phase) |
8.0; 10.4 | — |
| SECONDARY Time to Onset of Dementia at Week 156 (OLE Phase) |
38.18; 50.82 | — |
| SECONDARY Mean Change From Baseline in Free and Cued Selective Reminding Test (FCSRT) Score at Week 156 (OLE Phase) |
-7.7; -4.1 | — |
| SECONDARY Mean Change From Baseline in Functional Activities Questionnaire (FAQ) Score at Week 156 (OLE Phase) |
8.1; 6.8 | — |
| SECONDARY Mean Change From Baseline in CDR-Global Score at Week 156 (OLE Phase) |
0.6; 0.5 | — |
| SECONDARY Percentage Change From Baseline in Hippocampal Volume at Week 152 (OLE Phase) |
16.7; 16.1; 16.2; 18.0 | — |
| SECONDARY Percentage Change From Baseline in Cortical Composite Sustained Uptake Volume Ratio (SUVr) in Different Brain Regions at Week 156 (OLE Phase) |
-0.2; -41.4 | — |
| SECONDARY Gantenerumab Plasma Concentrations at Different Time Points (OLE Phase) |
33.0; 39.2; 80.5; 40.5; 45.2; 39.6 | — |
| SECONDARY Mean Change From Baseline in Mini Mental State Exam (MMSE) Score at Week 156 (OLE Phase) |
-4.3; -4.7 | — |
| SECONDARY Percentage of Participants With Anti-Drug Antibodies (ADAs) (OLE Phase) |
2.0; 5.8; 2.2; 2.9 | — |
Summary
This multi-center, randomized, double-blind, placebo-controlled parallel-group study will evaluate the effect of gantenerumab (RO4909832) on cognition and functioning and the safety and pharmacokinetics in participants with prodromal Alzheimer's Disease. Participants will be randomized to receive subcutaneous (SC) injections of either gantenerumab or placebo. Participants who consent to be part of the sub study will undergo positron emission tomography (PET) scanning to assess brain amyloid. The anticipated time on study treatment is 104 weeks in Part 1, with an option for an additional up to 2 years of treatment in Part 2, followed by an open-label extension (Part 3) until July 2020.
The dosing for Parts 1 and 2 was stopped after a planned futility interim analysis showed a low probability of meeting the primary outcome measure with the doses studied. The study has converted to open-label to investigate higher gantenerumab doses.
Eligibility Criteria
Inclusion Criteria
- Adult participants, 50-85 years of age
- Participants with prodromal Alzheimer's disease who are not receiving memantine or cholinesterase inhibitors
- Has a study partner who in the investigator's judgement has frequent and sufficient contact with the participant as to be able to provide accurate information as to the participant's cognitive and functional abilities, who agrees to provide information at clinic visits which require partner input for scale completion
- Has had sufficient education or work experience to exclude mental retardation
- Study partner has noticed a recent gradual decrease in participant's memory (over the last 12 months), which the participant may or may not be aware of
- Screening Mini Mental State Exam (MMSE) score of 24 or above
Additional inclusion criteria for sub study:
- Able and willing to travel to PET imaging center and complete the planned scanning sessions
- Past and planned exposure to ionizing radiation not exceeding safe and permissible levels
Exclusion Criteria
- Other prior or current neurologic or medical disorder which may currently or during the course of the study impair cognition or psychiatric functioning
- A history of stroke
- A documented history of transient ischemic attack within the last 12 months
- History of schizophrenia, schizoaffective or bipolar disorder
- Currently meets criteria for major depression
- Within the last 2 years, unstable or clinical significant cardiovascular disease (myocardial infarction, angina pectoris)
Additional exclusion criteria for sub study:
- Inclusion in a research and/or medical protocol involving PET ligands or other radioactive agents within 12 months
- Present or planned participation in a research and/or medical protocol involving PET ligands or radioactive agents other than study WN25203
- Have planned or are planning to have exposure to ionizing radiation that in combination with the planned administration with study amyloid PET ligand would result in a cumulative exposure that exceeds local recommended exposure limits
Data sourced from ClinicalTrials.gov (NCT01224106). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.