Immunocompromised Swiss Cohorts Based Trial Platform

Overview

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.

Full Title of Study: “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”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Randomized
    • Intervention Model: Parallel Assignment
    • Primary Purpose: Other
    • Masking: None (Open Label)
  • Study Primary Completion Date: July 2022

Detailed Description

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.

Interventions

  • 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

Arms, Groups and Cohorts

  • Active Comparator: Moderna mRNA COVID-19 vaccine
    • The Moderna COVID-19 Vaccine, mRNA-1273 (100 μg) is administered intramuscularly as a series of two doses (0.5 mL each), given 28 days apart.
  • Active Comparator: Comirnaty® (Pfizer / BioNTech) mRNA COVID-19 vaccine
    • Active: The comparator product is the first licensed vaccine against SARS-CoV-2 in Switzerland. Pfizer-BioNTech COVID-19 Vaccine, BNT162b2 (30 µg) Comirnaty®, is administered intramuscularly (IM) as a series of two 30 µg doses of the diluted vaccine solution (0.3 mL each) according to the following schedule: a single dose followed by a second dose 21 days later.

Clinical Trial Outcome Measures

Primary Measures

  • immunological outcome: change in pan-Ig antibody response (pan-Ig anti-S1-RBD)
    • Time Frame: at baseline (day of vaccination) and three months after vaccination
    • A commercial immunoassay Elecsys® Anti-SARS-CoV-2 S for the in vitro quantitative determination of antibodies to the SARS-CoV-2 spike (S) protein receptor binding domain (RBD) in human serum and plasma is used. This assay detects pan-Ig antibody response (pan-Ig anti-S1-RBD) and allows for a quantitative assessment of the serological response of the participants.
  • immunological outcome: change in anti-Nucleocapsid (N) response
    • Time Frame: at baseline (day of vaccination) and three months after vaccination
    • Qualitative measurement of anti-Nucleocapsid (N) responses with Elecsys® Anti-SARS-CoV-2 N assay
  • immunological outcome: change in SARS-CoV-2-binding antibodies
    • Time Frame: at baseline (day of vaccination) and three months after vaccination
    • SARS-CoV-2-binding antibody responses of the participants are assessed by analyzing the IgM, IgA and IgG responses to a wider range of SARS-CoV-2 proteins (S1, S2, RBD and N) using an in-house method (ABCORA). The ABCORA test allows a parallel assessment of IgG, IgM and IgA reactivity.
  • Number of participants with newly polymerase chain reaction (PCR)-confirmed asymptomatic COVID-19 infection
    • Time Frame: at any time point in within 48 weeks following randomisation (day of vaccination)
    • Number of participants with newly PCR-confirmed asymptomatic COVID-19 infection (identified by the presence of anti-SARS-CoV-2 nucleocapsid antibodies or Sars-Cov-2 PCR or rapid antigen test) and no related symptoms [(i.e. fever or chills, cough, shortness of breath or difficulty breathing, fatigue, muscle or body aches, headache, new loss of taste or smell, sore throat, congestion or runny nose nausea or vomiting, and diarrhea])
  • Number of participants with newly PCR-confirmed symptomatic COVID-19 infection
    • Time Frame: at any time point in within 48 weeks following randomisation (day of vaccination)
    • Number of participants with newly PCR-confirmed symptomatic COVID-19 infection with at least one of the following symptoms (i.e. fever or chills, cough, shortness of breath or difficulty breathing, fatigue, muscle or body aches, headache, new loss of taste or smell, sore throat, congestion or runny nose nausea or vomiting, and diarrhea
  • Number of participants with severe COVID-19 infection
    • Time Frame: at any time point in within 48 weeks following randomisation (day of vaccination)
    • Number of participants with severe COVID-19 infection with respiratory failure, evidence of shock (as diagnosed by a treating physician), clinically significant acute renal, hepatic, or neurologic dysfunction; admission to an intensive care unit; or death
  • Clinical Outcome: COVID-19 burden of diseases (BOD)
    • Time Frame: within 48 weeks following randomisation (day of vaccination)
    • COVID-19 burden of diseases (BOD), a composite, will be scored as by using 0 for no COVID-19, 1 for non-severe COVID-19, and 2 for severe COVID-19.
  • Duration of RCT set up (specific endpoint related to trial conduct feasibility)
    • Time Frame: one time assessment at baseline (from deciding which interventions will be tested until the first patient is randomised)
    • Duration of RCT set up (i.e. time from deciding which interventions will be tested until the first patient is randomised).
  • Time of patient recruitment from activation of first study site until 40 patients are randomised
    • Time Frame: one time assessment after approx. 3 months (from activation of first study site until 40 patients are randomised)
    • Time of patient recruitment from activation of first study site until 40 patients are randomised
  • Time of patient recruitment from activation of first study site until 380 patients are randomised
    • Time Frame: one time assessment after approx. 3 months (from activation of first study site until 380 patients are randomised)
    • Time of patient recruitment from activation of first study site until 380 patients are randomised
  • Patient consent rate
    • Time Frame: approx. 3 months
    • Patient consent rate (i.e. proportion of patients giving informed consent out of approached eligible patients)
  • Proportion of missing data for all baseline variables from routinely collected cohort data
    • Time Frame: one time assessment at baseline
    • Proportion of missing data for all baseline variables from routinely collected cohort data
  • Proportion of missing data for all clinical outcomes
    • Time Frame: one time assessment after approx. 3 months
    • Proportion of missing data for all clinical outcomes from routinely collected cohort data and outcome data that is collected in the trial platform
  • SARS-CoV-2-specific antibodies
    • Time Frame: three months after vaccination
    • SARS-CoV-2-specific antibodies (using a pan-IgG antibody assay against the receptor binding domain (RBD) against the nP and spike 1 subunits)
  • SARS-CoV-2-specific titers
    • Time Frame: three months after vaccination
    • SARS-CoV-2-specific titers (using an in-house assay developed by the Institute of Medical Virology, University of Zurich which can detect multiple viral epitopes)

Participating in This Clinical Trial

Inclusion Criteria

  • All patients registered with informed consent from participating cohorts aged ≥18 years – Additional consent for participation in the specific sub-protocol trial Inclusion criteria for pilot trial: – All patients with either a chronic HIV infection or recipients of solid organs registered with informed consent from the SHCS and STCS cohorts aged ≥18 years – Patients with solid organ transplantation of lungs or kidneys at least one month post-transplantation with a prednisone dose of 20mg or less. – Covid-19 vaccination recommended by treating physician Exclusion criteria:

  • Acute symptomatic SARS-CoV-2 infection, influenza or other acute respiratory tract infection – Known allergy or contra-indications for vaccines or any vaccine components – Any emergency condition requiring immediate hospitalization for any condition – Patients with previous PCR documented SARS-CoV-2 infection and, or documented antibodies less than 3 months prior to screening visit (day 0) Exclusion criteria for pilot trial: – Pregnancy – Acute symptomatic SARS-CoV-2 infection, influenza or other acute respiratory tract infection – Known allergy or contra-indications for vaccines or any vaccine components – Any emergency condition requiring immediate hospitalization for any condition – Patients with previous PCR documented SARS-CoV-2 infection and, or documented antibodies less than 3 months prior to randomisation – Patients with solid organ transplantation (lung or kidney) with the following conditions: 1. Solid organ transplant recipients less than one month post-transplantation 2. Solid organ transplant recipients with the use of T-cell/B-cell depleting agents in the last 3 months (i. e induction treatment in standard risk or high-risk immunological situation or rejection treatment). 3. Solid organ transplant recipients with the need of pulse corticosteroids (>100mg prednisone or equivalent) in the last 1 month or who have received ATG or rituximab in the last 6 months 4. Solid organ transplant recipients with the need of any kind of chemotherapy treatment

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: N/A

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • University Hospital, Basel, Switzerland
  • Collaborator
    • Swiss National Science Foundation
  • Provider of Information About this Clinical Study
    • Sponsor
  • Overall Official(s)
    • Heiner C. Bucher, Prof. Dr. med., Principal Investigator, Basel Institute for Clinical Epidemiology & Biostatistics, University Hospital Basel

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