Immunocompromised Swiss Cohorts Based Trial Platform

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).

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

Inclusion criteria

for 2. sub protocol (observational study):

• Third covid-19 vaccination recommended by treating physician and administered in the frame of clinical routine

Inclusion criteria

for 3. substudy.

• Patients receiving a new bivalent (Wuhan/Omicron BA.1) mRNA SARS-CoV-2 vaccine in the frame of clinical routine, according to the 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:

• Solid organ transplant recipients less than one month post-transplantation
• 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).
• 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
• Solid organ transplant recipients with the need of any kind of chemotherapy treatment