Adaptive Design for Phase II/III Platform Trial of Lassa Fever Therapeutics

Josephine Bourner; Michel Vaillant; Alex Paddy Abdel Salam; Marie Jaspard; Camille Fritzell; Shevin T Jacob; Tom E Fletcher; Michael Ramharter; Nnennaya Ajayi; Sylvanus Okogbenin; Cyril Erameh; Donald Grant; Robert Samuels; Oladele Oluwafemi Ayodeji; Armand Sprecher; Bronner P Gonçalves; Tansy Edwards; Piero Olliaro; WALC Work Package 2 Working Group

doi:10.3201/eid3102.240251

Adaptive Design for Phase II/III Platform Trial of Lassa Fever Therapeutics

Josephine Bourner^*
, Michel Vaillant
, Alex Paddy Abdel Salam
, Marie Jaspard
, Camille Fritzell
, Shevin T Jacob
, Tom E Fletcher
, Michael Ramharter
, Nnennaya Ajayi
, Sylvanus Okogbenin
, Cyril Erameh
, Donald Grant
, Robert Samuels
, Oladele Oluwafemi Ayodeji
, Armand Sprecher
, Bronner P Gonçalves
, Tansy Edwards
, Piero Olliaro
, WALC Work Package 2 Working Group

^*Corresponding author for this work

Competence Center for Methodology and Statistics

Research output: Contribution to journal › Article › Research › peer-review

Abstract

The current recommendation for treating Lassa fever with ribavirin is supported only by weak evidence. Given the persistent effects in areas with endemic transmission and epidemic potential, there is an urgent need to reassess ribavirin and investigate other potential therapeutic candidates; however, a robust clinical trial method adapted to Lassa fever epidemiology has not yet been established. We propose an adaptive phase II/III multicenter randomized controlled platform trial that uses a superiority framework with an equal allocation ratio and accounts for challenges selecting the primary end point and estimating the target sample size by using an interim analysis.

Original language	English
Pages (from-to)	9-16
Number of pages	8
Journal	Emerging Infectious Diseases
Volume	31
Issue number	2
DOIs	https://doi.org/10.3201/eid3102.240251
Publication status	Published - Feb 2025

Keywords

Lassa Fever/drug therapy
Humans
Antiviral Agents/therapeutic use
Lassa virus
Research Design
Ribavirin/therapeutic use
Clinical Trials, Phase II as Topic
Clinical Trials, Phase III as Topic

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Bourner, J., Vaillant, M., Abdel Salam, A. P., Jaspard, M., Fritzell, C., Jacob, S. T., Fletcher, T. E., Ramharter, M., Ajayi, N., Okogbenin, S., Erameh, C., Grant, D., Samuels, R., Ayodeji, O. O., Sprecher, A., Gonçalves, B. P., Edwards, T., Olliaro, P., & WALC Work Package 2 Working Group (2025). Adaptive Design for Phase II/III Platform Trial of Lassa Fever Therapeutics. Emerging Infectious Diseases, 31(2), 9-16. https://doi.org/10.3201/eid3102.240251

@article{a7f77623a0564bc1b6232b7e26d49f2e,

title = "Adaptive Design for Phase II/III Platform Trial of Lassa Fever Therapeutics",

abstract = "The current recommendation for treating Lassa fever with ribavirin is supported only by weak evidence. Given the persistent effects in areas with endemic transmission and epidemic potential, there is an urgent need to reassess ribavirin and investigate other potential therapeutic candidates; however, a robust clinical trial method adapted to Lassa fever epidemiology has not yet been established. We propose an adaptive phase II/III multicenter randomized controlled platform trial that uses a superiority framework with an equal allocation ratio and accounts for challenges selecting the primary end point and estimating the target sample size by using an interim analysis.",

keywords = "Lassa Fever/drug therapy, Humans, Antiviral Agents/therapeutic use, Lassa virus, Research Design, Ribavirin/therapeutic use, Clinical Trials, Phase II as Topic, Clinical Trials, Phase III as Topic",

author = "Josephine Bourner and Michel Vaillant and \{Abdel Salam\}, \{Alex Paddy\} and Marie Jaspard and Camille Fritzell and Jacob, \{Shevin T\} and Fletcher, \{Tom E\} and Michael Ramharter and Nnennaya Ajayi and Sylvanus Okogbenin and Cyril Erameh and Donald Grant and Robert Samuels and Ayodeji, \{Oladele Oluwafemi\} and Armand Sprecher and Gon{\c c}alves, \{Bronner P\} and Tansy Edwards and Piero Olliaro and \{WALC Work Package 2 Working Group\}",

note = "Funding: The work undertaken within the scope of the WALC was supported by Wellcome.",

year = "2025",

month = feb,

doi = "10.3201/eid3102.240251",

language = "English",

volume = "31",

pages = "9--16",

journal = "Emerging Infectious Diseases",

issn = "1080-6040",

publisher = "Centers for Disease Control and Prevention (CDC)",

number = "2",

}

Bourner, J, Vaillant, M, Abdel Salam, AP, Jaspard, M, Fritzell, C, Jacob, ST, Fletcher, TE, Ramharter, M, Ajayi, N, Okogbenin, S, Erameh, C, Grant, D, Samuels, R, Ayodeji, OO, Sprecher, A, Gonçalves, BP, Edwards, T, Olliaro, P & WALC Work Package 2 Working Group 2025, 'Adaptive Design for Phase II/III Platform Trial of Lassa Fever Therapeutics', Emerging Infectious Diseases, vol. 31, no. 2, pp. 9-16. https://doi.org/10.3201/eid3102.240251

TY - JOUR

T1 - Adaptive Design for Phase II/III Platform Trial of Lassa Fever Therapeutics

AU - Bourner, Josephine

AU - Vaillant, Michel

AU - Abdel Salam, Alex Paddy

AU - Jaspard, Marie

AU - Fritzell, Camille

AU - Jacob, Shevin T

AU - Fletcher, Tom E

AU - Ramharter, Michael

AU - Ajayi, Nnennaya

AU - Okogbenin, Sylvanus

AU - Erameh, Cyril

AU - Grant, Donald

AU - Samuels, Robert

AU - Ayodeji, Oladele Oluwafemi

AU - Sprecher, Armand

AU - Gonçalves, Bronner P

AU - Edwards, Tansy

AU - Olliaro, Piero

AU - WALC Work Package 2 Working Group

N1 - Funding: The work undertaken within the scope of the WALC was supported by Wellcome.

PY - 2025/2

Y1 - 2025/2

N2 - The current recommendation for treating Lassa fever with ribavirin is supported only by weak evidence. Given the persistent effects in areas with endemic transmission and epidemic potential, there is an urgent need to reassess ribavirin and investigate other potential therapeutic candidates; however, a robust clinical trial method adapted to Lassa fever epidemiology has not yet been established. We propose an adaptive phase II/III multicenter randomized controlled platform trial that uses a superiority framework with an equal allocation ratio and accounts for challenges selecting the primary end point and estimating the target sample size by using an interim analysis.

AB - The current recommendation for treating Lassa fever with ribavirin is supported only by weak evidence. Given the persistent effects in areas with endemic transmission and epidemic potential, there is an urgent need to reassess ribavirin and investigate other potential therapeutic candidates; however, a robust clinical trial method adapted to Lassa fever epidemiology has not yet been established. We propose an adaptive phase II/III multicenter randomized controlled platform trial that uses a superiority framework with an equal allocation ratio and accounts for challenges selecting the primary end point and estimating the target sample size by using an interim analysis.

KW - Lassa Fever/drug therapy

KW - Humans

KW - Antiviral Agents/therapeutic use

KW - Lassa virus

KW - Research Design

KW - Ribavirin/therapeutic use

KW - Clinical Trials, Phase II as Topic

KW - Clinical Trials, Phase III as Topic

UR - https://pubmed.ncbi.nlm.nih.gov/39983682/

U2 - 10.3201/eid3102.240251

DO - 10.3201/eid3102.240251

M3 - Article

C2 - 39983682

SN - 1080-6040

VL - 31

SP - 9

EP - 16

JO - Emerging Infectious Diseases

JF - Emerging Infectious Diseases

IS - 2

ER -

Adaptive Design for Phase II/III Platform Trial of Lassa Fever Therapeutics

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