Trials (Oct 2021)

A trial platform to assess approved SARS-CoV-2 vaccines in immunocompromised patients: first sub-protocol for a pilot trial comparing the mRNA vaccines Comirnaty® and COVID-19 mRNA Vaccine Moderna®

  • Benjamin Speich,
  • Frédérique Chammartin,
  • Daniel Smith,
  • Marcel P. Stoeckle,
  • Patrizia Amico,
  • Anna L. Eichenberger,
  • Barbara Hasse,
  • Macé M. Schuurmans,
  • Thomas Müller,
  • Michael Tamm,
  • Michael Dickenmann,
  • Irene A. Abela,
  • Alexandra Trkola,
  • Hans H. Hirsch,
  • Oriol Manuel,
  • Matthias Cavassini,
  • Lars G. Hemkens,
  • Matthias Briel,
  • Nicolas J. Mueller,
  • Andri Rauch,
  • Huldrych F. Günthard,
  • Michael T. Koller,
  • Heiner C. Bucher,
  • Katharina Kusejko,
  • in collaboration with the study groups from the Swiss HIV Cohort Study and the Swiss Transplant Cohort Study

DOI
https://doi.org/10.1186/s13063-021-05664-0
Journal volume & issue
Vol. 22, no. 1
pp. 1 – 16

Abstract

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Abstract Background Late 2019, a new highly contagious coronavirus SARS-CoV-2 has emerged in Wuhan, China, causing within 2 months a pandemic with the highest disease burden in elderly and people with pre-existing medical conditions. The pandemic has highlighted that new and more flexible clinical trial approaches, such as trial platforms, are needed to assess the efficacy and safety of interventions in a timely manner. The two existing Swiss cohorts of immunocompromised patients (i.e., Swiss HIV Cohort Study (SHCS) and Swiss Transplant Cohort Study (STCS)) are an ideal foundation to set-up a trial platform in Switzerland leveraging routinely collected data. Within a newly founded trial platform, we plan to assess the efficacy of the first two mRNA SARS-CoV-2 vaccines that reached market authorization in Switzerland in the frame of a pilot randomized controlled trial (RCT) while at the same time assessing the functionality of the trial platform. Methods We will conduct a multicenter randomized controlled, open-label, 2-arm sub-study pilot trial of a platform trial nested into two Swiss cohorts. Patients included in the SHCS or the STCS will be eligible for randomization to either receiving the mRNA vaccine Comirnaty® (Pfizer/BioNTech) or the COVID-19 mRNA Vaccine Moderna®. The primary clinical outcome will be change in pan-lg antibody response (pan-Ig anti-S1-RBD; baseline vs. 3 months after first vaccination; binary outcome, considering ≥ 0.8 units/ml as a positive antibody response). The pilot study will also enable us to assess endpoints related to trial conduct feasibility (i.e., duration of RCT set-up; time of patient recruitment; patient consent rate; proportion of missing data). Assuming vaccine reactivity of 90% in both vaccine groups, we power our trial, using a non-inferiority margin such that a 95% two-sided confidence interval excludes a difference in favor of the reference group of more than 10%. A sample size of 380 (190 in each treatment arm) is required for a statistical power of 90% and a type I error of 0.025. The study is funded by the Swiss National Science Foundation (National Research Program NRP 78, “COVID-19”). Discussion This study will provide crucial information about the efficacy and safety of the mRNA SARS-CoV-2 vaccines in HIV patients and organ transplant recipients. Furthermore, this project has the potential to pave the way for further platform trials in Switzerland. Trial registration ClinicalTrials.gov NCT04805125 . Registered on March 18, 2021

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