ArticleAlzheimer's & dementia (New York, N. Y.)2016
Design of a Bayesian adaptive phase 2 proof-of-concept trial for BAN2401, a putative disease-modifying monoclonal antibody for the treatment of Alzheimer's disease.
Article in Alzheimer's & dementia (New York, N. Y.), 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers, 1 of them a synthesis that pooled it.
What it found
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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.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
36 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Effect of reductions in amyloid levels on cognitive change in randomized trials: instrumental variable meta-analysis.BMJ (Clinical research ed.) · 2021Pooled it
- Lecanemab for Patients With Early Alzheimer Disease: Bayesian Analysis of a Phase 2b Dose-Finding Randomized Clinical Trial.JAMA network open · 2023Trial
- A randomized, double-blind, phase 2b proof-of-concept clinical trial in early Alzheimer's disease with lecanemab, an anti-Aβ protofibril antibody.Alzheimer's research & therapy · 2021Trial
- Lecanemab appropriate use recommendations for clinical practice in the UK.Journal of neurology, neurosurgery, and psychiatry · 2026Review
- Alzheimer Combination Therapies: Overview and Scenarios.The journal of prevention of Alzheimer's disease · 2025Review
- Adaptive Bayesian Clinical Trials: The Past, Present, and Future of Clinical Research.Journal of clinical medicine · 2025Article
- Chemical imaging delineates Aβ plaque polymorphism across the Alzheimer's disease spectrum.Nature communications · 2025Article
- Pathways to personalized medicine-Embracing heterogeneity for progress in clinical therapeutics research in Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2024Review
- Food and Drug Administration (FDA) Approvals of Biological Drugs in 2023.Biomedicines · 2024Review
- Chemical signatures delineate heterogeneous amyloid plaque populations across the Alzheimer's disease spectrum.bioRxiv : the preprint server for biology · 2024Article
- A multimodal deep learning approach for the prediction of cognitive decline and its effectiveness in clinical trials for Alzheimer's disease.Translational psychiatry · 2024Article
- Amyloid-Directed Antibodies: Past, Present, and Future.Journal of Alzheimer's disease : JAD · 2024Review
- From Recognition to Remedy: The Significance of Biomarkers in Neurodegenerative Disease Pathology.International journal of molecular sciences · 2023Review
- Lecanemab (BAN2401): an anti-beta-amyloid monoclonal antibody for the treatment of Alzheimer disease.Expert opinion on investigational drugs · 2023Review
- Lecanemab: Appropriate Use Recommendations.The journal of prevention of Alzheimer's disease · 2023Article
- The amyloid hypothesis in Alzheimer disease: new insights from new therapeutics.Nature reviews. Drug discovery · 2022Review
- Review of Advanced Drug Trials Focusing on the Reduction of Brain Beta-Amyloid to Prevent and Treat Dementia.Journal of experimental pharmacology · 2022Review
- Review
- Amyloid Oligomers: A Joint Experimental/Computational Perspective on Alzheimer's Disease, Parkinson's Disease, Type II Diabetes, and Amyotrophic Lateral Sclerosis.Chemical reviews · 2021Review
- Amyloid-β and α-Synuclein Immunotherapy: From Experimental Studies to Clinical Trials.Frontiers in neuroscience · 2021Review
Corrections and comments
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Authors and funding
7 authors.
Funding
Abstract
introductionRecent failures in phase 3 clinical trials in Alzheimer's disease (AD) suggest that novel approaches to drug development are urgently needed. Phase 3 risk can be mitigated by ensuring that clinical efficacy is established before initiating confirmatory trials, but traditional phase 2 trials in AD can be lengthy and costly.
methodsWe designed a Bayesian adaptive phase 2, proof-of-concept trial with a clinical endpoint to evaluate BAN2401, a monoclonal antibody targeting amyloid protofibrils. The study design used dose response and longitudinal modeling. Simulations were used to refine study design features to achieve optimal operating characteristics.
resultsThe study design includes five active treatment arms plus placebo, a clinical outcome, 12-month primary endpoint, and a maximum sample size of 800. The average overall probability of success is ≥80% when at least one dose shows a treatment effect that would be considered clinically meaningful. Using frequent interim analyses, the randomization ratios are adapted based on the clinical endpoint, and the trial can be stopped for success or futility before full enrollment. DISCUSSION: Bayesian statistics can enhance the efficiency of analyzing the study data. The adaptive randomization generates more data on doses that appear to be more efficacious, which can improve dose selection for phase 3. The interim analyses permit stopping as soon as a predefined signal is detected, which can accelerate decision making. Both features can reduce the size and duration of the trial. This study design can mitigate some of the risks associated with advancing to phase 3 in the absence of data demonstrating clinical efficacy. Limitations to the approach are discussed.
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