NCT04805125

Immunocompromised Swiss Cohorts Based Trial Platform

Randomised Controlled Trials to Assess Approved SARS-CoV-2 Vaccines in Immunocompromised Patients: A Master Protocol for the Set-up of a Swiss Cohorts Based Trial Platform

• Status: Completed
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 610 (actual)
• Sponsor: University Hospital, Basel, Switzerland · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This study is to set up a flexible trial platform using two existing national cohorts of immunocompromised patients (i.e. Swiss HIV Cohort Study \[SHCS\] and Swiss Transplant Cohort Study \[STCS\]) to assess the comparative effectiveness and safety of approved SARS-CoV-2 vaccines in immunocompromised patients. This platform will be tested in the frame of an exploratory pilot trial and a framework will be set up to conduct a larger, flexible, randomized controlled trial (RCT) to test approved SARS-CoV-2 vaccines to prevent SARS-CoV-2 infections. The first sub-protocol for a pilot trial is to investigate the operability of a platform trial that is nested into two existing cohort studies and compare immune response, safety and clinical efficacy of the first two mRNA vaccines (Comirnaty® by Pfizer / BioNTech and COVID-19 mRNA Vaccine Moderna®, by Moderna) in immune compromised patients in the Swiss HIV and Swiss Transplant Cohort studies. The second sub-protocol (observational study) is to collect a blood sample before the third vaccination and 8 weeks after vaccination to analyze an additional benefit of a third SARS-CoV-2 vaccine in these immunocompromised patients. In the third sub-protocol (substudy-3; observational) we will recruit patients who have received m-RNA-1273.214 by Moderna in the frame of clinical routine. We will start a second arm of our observational study as soon as another bivalent mRNA vaccine (from Pfizer-BioNTech) has been approved by Swissmedic. We aim to compare the immunologic response and safety of the bivalent mRNA-1273.214 vaccine from Moderna among immunocompromised persons (persons living with HIV or kidney or lung transplant recipients) to the immunologic response of immunocompromised persons who received the bivalent mRNA vaccine from Pfizer-BioNTech.

Detailed description

The aim of this study is to set up a flexible trial platform using two existing national cohorts of immunocompromised patients (i.e. Swiss HIV Cohort Study \[SHCS\] and Swiss Transplant Cohort Study \[STCS\]) to assess the comparative effectiveness and safety of approved SARS-CoV-2 vaccines in immunocompromised patients. Nesting this trial into cohorts with highly standardized data collection allows for a rapid, efficient and cost-saving trial conduct. This platform will be tested in the frame of a pilot trial and a framework will be set up to conduct a larger, flexible, randomized controlled trial (RCT) to test approved SARS-CoV-2 vaccines to prevent SARS-CoV-2 infections. The pilot study will primarily assess the functionality of the trial platform and early immunogenicity, efficacy and safety data. At a later stage, the platform might also be used to enlarge the pilot trial or to develop sub-protocols to deal with patients with no or insufficient immune response to Sars-CoV-2 vaccines. Since January 12, 2021 two mRNA vaccines against Sars-CoV-2 by Pfizer / BioNTech (Comirnaty®) and COVID-19 mRNA Vaccine Moderna® by Moderna have been licensed in Switzerland and roll-out of vaccines has started The first sub-protocol for a pilot trial is to investigate the operability of a platform trial that is nested into two existing cohort studies and compare immune response, safety and clinical efficacy of the first two mRNA vaccines (Comirnaty® by Pfizer / BioNTech and COVID-19 mRNA Vaccine Moderna®, by Moderna) in immune compromised patients in the Swiss HIV and Swiss Transplant Cohort studies. In Switzerland, since October 2021 severely immunodeficient persons ≥ 12 years of age who have received two doses of an mRNA vaccine should receive a third dose of Comirnaty® or Spikevax® as part of the basic immunization, regardless of any antibody titer. Among all other immunocompromised patients a booster vaccination with an mRNA vaccine is recommended. These vaccines will be administered to patients from the SHCS and the STCS in the frame of clinical routine. This second sub-protocol (observational study) is to collect a blood sample before the third vaccination and 8 weeks after vaccination to analyze an additional benefit of a third SARS-CoV-2 vaccine in these immunocompromised patients. In the third sub-protocol (substudy-3; observational) we will recruit patients who have received m-RNA-1273.214 by Moderna in the frame of clinical routine. We will start a second arm of our observational study as soon as another bivalent mRNA vaccine (from Pfizer-BioNTech) has been approved by Swissmedic. We aim to compare the immunologic response and safety of the bivalent mRNA-1273.214 vaccine from Moderna (n=160) among immunocompromised persons (persons living with HIV or kidney or lung transplant recipients) to the immunologic response of immunocompromised persons who received the bivalent mRNA vaccine from Pfizer-BioNTech (n=80). Patients will be asked to provide blood sample at baseline (before receiving bivalent mRNA SARS-CoV-2 vaccine) and 4 weeks, 8 weeks, and 6 months after vaccination (see details in original study protocol below).

Conditions

• Immunocompromised Patients

Interventions

Type	Name	Description
BIOLOGICAL	Moderna COVID-19 Vaccine, mRNA-1273 (100 μg)	intramuscular injection, proposed as a series of two doses (0.5 mL each), dosing is 100 microgram on day 0 and day 28
BIOLOGICAL	Pfizer-BioNTech COVID-19 Vaccine BNT162b2 (30 µg)( Comirnaty®)	intramuscular injection, proposed dosing is 30 microgram of the diluted vaccine solution (0.3 mL each) on day 0 and day 21

Timeline

• Start date: 2021-04-19
• Primary completion: 2023-09-23
• Completion: 2023-09-23
• First posted: 2021-03-18
• Last updated: 2024-01-25

Locations

4 sites across 1 country: Switzerland