Designing an exploratory phase 2b platform trial in NASH with correlated, co-primary binary endpoints

Elias Laurin Meyer; Peter Mesenbrink; Nicholas A Di Prospero; Juan M Pericàs; Ekkehard Glimm; Vlad Ratziu; Elena Sena; Franz König; EU-PEARL NASH Investigators

doi:10.1371/journal.pone.0281674

Designing an exploratory phase 2b platform trial in NASH with correlated, co-primary binary endpoints

PLoS One. 2023 Mar 9;18(3):e0281674. doi: 10.1371/journal.pone.0281674. eCollection 2023.

Authors

Elias Laurin Meyer¹, Peter Mesenbrink², Nicholas A Di Prospero³, Juan M Pericàs^{4

5}, Ekkehard Glimm^{6

7}, Vlad Ratziu⁸, Elena Sena⁴, Franz König¹; EU-PEARL NASH Investigators

Affiliations

¹ Center for Medical Data Science, Medical University of Vienna, Vienna, Austria.
² Novartis Pharmaceuticals Corporation, One Health Plaza, East Hanover, NJ, United States of America.
³ Janssen Research and Development, Raritan, NJ, United States of America.
⁴ Liver Unit, Internal Medicine Department, Vall d'Hebron University Hospital, Vall d'Hebron Institute for Research (VHIR), Barcelona, Spain.
⁵ Centros de Investigación Biomédica en Red Enfermedades Hepáticas y Digestivas (CIBERehd), ISCIII, Madrid, Spain.
⁶ Novartis Pharma AG, Basel, Switzerland.
⁷ Institute of Biometry and Medical Informatics, University of Magdeburg, Magdeburg, Germany.
⁸ Assistance Publique-Hôpitaux de Paris, Hôpital Pitie-Salpetriere, University of Paris, Paris, France.

Abstract

Non-alcoholic steatohepatitis (NASH) is the progressive form of nonalcoholic fatty liver disease (NAFLD) and a disease with high unmet medical need. Platform trials provide great benefits for sponsors and trial participants in terms of accelerating drug development programs. In this article, we describe some of the activities of the EU-PEARL consortium (EU Patient-cEntric clinicAl tRial pLatforms) regarding the use of platform trials in NASH, in particular the proposed trial design, decision rules and simulation results. For a set of assumptions, we present the results of a simulation study recently discussed with two health authorities and the learnings from these meetings from a trial design perspective. Since the proposed design uses co-primary binary endpoints, we furthermore discuss the different options and practical considerations for simulating correlated binary endpoints.

Copyright: © 2023 Meyer et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Clinical Trials, Phase II as Topic
Endpoint Determination
Humans
Non-alcoholic Fatty Liver Disease* / drug therapy
Research Design

Grants and funding

EU-PEARL has received funding from the Innovative Medicines Initiative 2 Joint Undertaking under grant agreement No 853966-2. This Joint Undertaking receives support from the European Union’s Horizon 2020 research and innovation programme and EFPIA and CHILDREN’S TUMOR FOUNDATION, GLOBAL ALLIANCE FOR TB DRUG DEVELOPMENT NON PROFIT ORGANISATION, SPRINGWORKS THERAPEUTICS INC. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.