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A phase III randomized trial of gantenerumab in prodromal Alzheimer's disease
Ostrowitzki S, Lasser RA, Dorflinger E, Scheltens P, Barkhof F, Nikolcheva T, Ashford E, Retout S et al.. Alzheimer's research & therapy, 2017-12-08
Topic: Amyloid, tau and blood-test diagnosis
Background Gantenerumab is a fully human monoclonal antibody that binds aggregated amyloid-β (Aβ) and removes Aβ plaques by Fc receptor-mediated phagocytosis. In the SCarlet RoAD trial, we assessed the efficacy and safety of gantenerumab in prodromal Alzheimer's disease (AD). Methods In this randomized, double-blind, placebo-controlled phase III study, we investigated gantenerumab over 2 years. Patients were randomized to gantenerumab 105 mg or 225 mg or placebo every 4 weeks by subcutaneous injection. The primary endpoint was the change from baseline to week 104 in Clinical Dementia Rating Sum of Boxes (CDR-SB) score. We evaluated treatment effects on cerebrospinal fluid biomarkers (all patients) and amyloid positron emission tomography (substudy). A futility analysis was performed once 50% of patients completed 2 years of treatment. Safety was assessed in patients who received at least one dose. Results Of the 3089 patients screened, 797 were randomized. The study was halted early for futility; dosing was discontinued; and the study was unblinded. No differences between groups in the primary (least squares mean [95% CI] CDR-SB change from baseline 1.60 [1.28, 1.91], 1.69 [1.37, 2.01], and 1.73 [1.42, 2.04] for placebo, gantenerumab 105 mg, and gantenerumab 225 mg, respectively) or secondary clinical endpoints were observed. The incidence of generally asymptomatic amyloid-related imaging abnormalities increased in a dose- and APOE ε4 genotype-dependent manner. Exploratory analyses suggested a dose-dependent drug effect on clinical and biomarker endpoints. Conclusions The study was stopped early for futility, but dose-dependent effects observed in exploratory analyses on select clinical and biomarker endpoints suggest that higher dosing with gantenerumab may be necessary to achieve clinical efficacy. Trial registration ClinicalTrials.gov, NCT01224106 . Registered on October 14, 2010.
Key findings
- Results Of the 3089 patients screened, 797 were randomized.
- Conclusions The study was stopped early for futility, but dose-dependent effects observed in exploratory analyses on select clinical and biomarker endpoints suggest that higher dosing with gantenerumab may be necessary to achieve clinical efficacy.
Why it matters
In this 2-year phase III trial (SCarlet RoAD), 797 people with prodromal Alzheimer's disease were randomized to monthly injections of gantenerumab 105 mg, 225 mg or placebo. The trial was stopped early for futility, with no difference from placebo on the main measure of decline (CDR-SB) or on secondary clinical measures. Brain-scan changes called ARIA, mostly without symptoms, became more common with higher dose and in APOE ε4 carriers; the authors' suggestion that higher doses might be needed comes from exploratory analyses only.
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Study details
- Participants3,089
- Evidence strengthHigh
How this study scored 78/100
Published in a peer-reviewed journal, and it is a large phase 3 trial. Scored zero for effect reported because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Alzheimer's research & therapy) |
| Journal's citation record | 1 / 4 | Alzheimer s Research & Therapy: journal h-index 146 (OpenAlex, 2026-10-29) |
| Study design | 11 / 12 | A large phase 3 trial (from PubMed type “Clinical Trial, Phase III”) |
| Strength of evidence | 5 / 5 | Rated “high” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 2 / 5 | 2017 — within 10 year(s) of the newest study here |
| Sample size | 3 / 4 | 3,089 participants |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 3 / 3 | Studied in people (participant count stated) |
| Randomised / blinded | 2 / 2 | Randomised and blinded or placebo-controlled (as stated in the record) |
| Times cited | 6 / 7 | Cited 567 times (OpenAlex, 2026-10-10) |
| Citations per year | 5 / 5 | 51.5 citations a year over 11 year(s) since 2017 |
| Impact for its field and year | 5 / 6 | Cited 29.3× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 4 / 6 | Cited by 42 other studies in this library |
| Still being cited | 3 / 4 | Cited 157 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 2 / 4 | Last-listed author Paulo Fontoura: h-index 42 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | University College London: institution h-index 2,029 (OpenAlex) |
| Multi-centre collaboration | 3 / 3 | OpenAlex lists 10 institution(s) in 6 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 29221491) |
| Free to read | 2 / 2 | Free to read |
| Total | 78 / 100 | — |
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Read the original
- DOI: 10.1186/s13195-017-0318-y
- PubMed: 29221491
- Original source →
- Free full text: Alzheimer s Research & Therapy →
Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
Built from the record alzhub holds for this paper, not looked up. Volume, issue and page numbers are not held in the record. The record's author list ends in “et al.”, so not every author is named. Check the citation against the original before you use it.
APA 7th
Ostrowitzki, S., Lasser, R. A., Dorflinger, E., Scheltens, P., Barkhof, F., Nikolcheva, T., et al. (2017). A phase III randomized trial of gantenerumab in prodromal Alzheimer's disease. Alzheimer's research & therapy. https://doi.org/10.1186/s13195-017-0318-y
Vancouver
Ostrowitzki S, Lasser RA, Dorflinger E, Scheltens P, Barkhof F, Nikolcheva T, et al. A phase III randomized trial of gantenerumab in prodromal Alzheimer's disease. Alzheimer's research & therapy. 2017. doi:10.1186/s13195-017-0318-y. PMID: 29221491.
BibTeX
@article{ostrowitzki2017-29221491,
author = {Ostrowitzki, S. and Lasser, R. A. and Dorflinger, E. and Scheltens, P. and Barkhof, F. and Nikolcheva, T. and Ashford, E. and Retout, S. and others},
title = {{A phase III randomized trial of gantenerumab in prodromal Alzheimer's disease}},
journal = {Alzheimer's research \& therapy},
year = {2017},
doi = {10.1186/s13195-017-0318-y},
pmid = {29221491},
url = {https://doi.org/10.1186/s13195-017-0318-y}
}
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