Evidence map›Paper›PMID 29221491›Full record

Trial reportAlzheimer's research & therapy2017

A phase III randomized trial of gantenerumab in prodromal Alzheimer's disease.

Susanne Ostrowitzki, Robert A Lasser, Ernest Dorflinger, Philip Scheltens, Frederik Barkhof, Tania Nikolcheva, Elizabeth Ashford, Sylvie Retout, Carsten Hofmann, Paul Delmar and 8 more

Erratum issued Registry-linked trialAbstract readClinical Trial, Phase IIIMulticenter StudyRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Alzheimer's research & therapy, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. It is linked to trial NCT01224106 (Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Two Year Study to Evaluate the Effect of Subcutaneous RO4909832 on Cognition and Function in Prodromal Alzheimer's Disease With Option for up to an Additional Two Years of Treatment and an Open-Label Extension With Active Study Treatment), which is not on this map. Cited by 284 papers, 14 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
284citing papers in PubMed, 14 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT01224106 phase3completednot on this map

Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Two Year Study to Evaluate the Effect of Subcutaneous RO4909832 on Cognition and Function in Prodromal Alzheimer's Disease With Option for up to an Additional Two Years of Treatment and an Open-Label Extension With Active Study Treatment

TypeinterventionalSponsorHoffmann-La RocheRan2010 to 2020Enrolled799ConditionsAlzheimer's DiseaseArmsGantenerumab, Placebo
3 · Its place in the literature

Who cites it

284 citing papers in PubMed, 14 syntheses or guidelines pooled it.

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  6. Efficacy of anti-amyloid-ß monoclonal antibody therapy in early Alzheimer's disease: a systematic review and meta-analysis.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2024
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  14. Bayes analysis supports null hypothesis of anti-amyloid beta therapy in Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2021
    Pooled it
  15. A randomized phase 1b/2 trial of ABBV-916 in adults with early Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026
    Trial
  16. Regional effects of gantenerumab on neuroimaging biomarkers in the DIAN-TU-001 trial.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025
    Trial
  17. Japanese participant data from three gantenerumab trials in early Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025
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  20. Results from the long-term extension of PRIME: A randomized Phase 1b trial of aducanumab.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2024
    Trial

224 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

18 authors.

Susanne OstrowitzkiProduct Development, Neuroscience, Genentech Inc., South San Francisco, CA, USA.
Robert A LasserMedDay Pharmaceuticals, Boston, MA, USA.
Ernest DorflingerFormerly Roche Translational & Clinical Research Center, New York, NY, USA.
Philip ScheltensVU University Medical Center, Amsterdam, The Netherlands.
Frederik BarkhofVU University Medical Center, Amsterdam, The Netherlands.
Tania NikolchevaRoche Pharma Research and Early Development, NORD, Basel, Switzerland.
Elizabeth AshfordRoche Products Limited, Welwyn Garden City, UK.
Sylvie RetoutRoche Pharma Research and Early Development, Clinical Pharmacology, Roche Innovation Center, Basel, Switzerland.
Carsten HofmannRoche Pharma Research and Early Development, Clinical Pharmacology, Roche Innovation Center, Basel, Switzerland.
Paul DelmarClinical Pharmacology and Bioanalytical R&D, Pharmaceutical Sciences, Roche Pharma Research and Early Development, Roche Innovation Center Basel, Basel, Switzerland.
Gregory KleinRoche Pharma Research and Early Development, NORD, Basel, Switzerland.
Mirjana AndjelkovicRoche Pharma Research and Early Development, Clinical Pharmacology, Roche Innovation Center, Basel, Switzerland.
Bruno DuboisAlzheimer Institute and ICM, UMR-S975, Salpêtrière University Hospital, AP-HP, Pierre and Marie Curie University, Paris, France.
Mercè BoadaResearch Center and Memory Clinic of Fundació ACE, Institut Català de Neurociències Aplicades, Barcelona, Spain.
Kaj BlennowResearch Center and Memory Clinic of Fundació ACE, Institut Català de Neurociències Aplicades, Barcelona, Spain.
Luca SantarelliFormerly Roche Pharma Research and Early Development, NORD, Basel, Switzerland.
Paulo FontouraClinical Pharmacology and Bioanalytical R&D, Pharmaceutical Sciences, Roche Pharma Research and Early Development, Roche Innovation Center Basel, Basel, Switzerland. paulo.fontoura@roche.com.
SCarlet RoAD Investigators

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundGantenerumab 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).

methodsIn 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.

resultsOf 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.

conclusionsThe 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 registrationClinicalTrials.gov, NCT01224106 . Registered on October 14, 2010.

Indexed as

Prodromal SymptomsAgedAlzheimer DiseaseAmyloid beta-PeptidesAntibodies, MonoclonalAntibodies, Monoclonal, HumanizedApolipoprotein E4Dose-Response Relationship, DrugDouble-Blind MethodHumansImmunologic FactorsLongitudinal StudiesMagnetic Resonance ImagingMiddle AgedNeuropsychological TestsPositron-Emission TomographyAmyloid beta-PeptidesAntibodies, MonoclonalAntibodies, Monoclonal, HumanizedApolipoprotein E4gantenerumabImmunologic FactorsAlzheimer’s diseaseGantenerumabSCarlet RoAD

Identifiers

PMID29221491
PMCPMC5723032

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Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.