Immunocompromised Swiss Cohorts Based Trial Platform

NCT ID: NCT04805125

Last Updated: 2024-01-25

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 610 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-04-19
• Study Completion Date: 2023-09-23

Brief 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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: OTHER
• Blinding Strategy: NONE

Study Groups

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.

ARM CLOSED

Group Type: ACTIVE_COMPARATOR

Moderna COVID-19 Vaccine, mRNA-1273 (100 μg)

Intervention Type: BIOLOGICAL

intramuscular injection, proposed as a series of two doses (0.5 mL each), dosing is 100 microgram on day 0 and day 28

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.

ARM CLOSED

Group Type: ACTIVE_COMPARATOR

Pfizer-BioNTech COVID-19 Vaccine BNT162b2 (30 µg)( Comirnaty®)

Intervention Type: BIOLOGICAL

intramuscular injection, proposed dosing is 30 microgram of the diluted vaccine solution (0.3 mL each) on day 0 and day 21

Interventions

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

Intervention Type: 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

Intervention Type: BIOLOGICAL

Eligibility Criteria

Inclusion Criteria

• All patients registered with informed consent from participating cohorts aged ≥18 years
• Additional consent for participation in the specific sub-protocol 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

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

• 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)

• 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Swiss National Science Foundation

OTHER

Sponsor Role: collaborator

ModernaTX, Inc.

INDUSTRY

Sponsor Role: collaborator

University Hospital, Basel, Switzerland

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Heiner C. Bucher, Prof. Dr. med.

Role: PRINCIPAL_INVESTIGATOR

Basel Institute for Clinical Epidemiology & Biostatistics, University Hospital Basel

Locations

University Hospital Basel

Basel, , Switzerland

University Hospital Bern

Bern, , Switzerland

University Hospital Lausanne CHUV

Lausanne, , Switzerland

University Hospital Zurich

Zurich, , Switzerland

Countries

Switzerland

References

Speich B, Chammartin F, Abela IA, Amico P, Stoeckle MP, Eichenberger AL, Hasse B, Braun DL, Schuurmans MM, Muller TF, Tamm M, Audige A, Mueller NJ, Rauch A, Gunthard HF, Koller MT, Trkola A, Briel M, Kusejko K, Bucher HC; Swiss HIV Cohort Study and the Swiss Transplant Cohort Study. Antibody Response in Immunocompromised Patients After the Administration of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Vaccine BNT162b2 or mRNA-1273: A Randomized Controlled Trial. Clin Infect Dis. 2022 Aug 24;75(1):e585-e593. doi: 10.1093/cid/ciac169.

Reference Type: RESULT

PMID: 35234868 (View on PubMed)

Kusejko K, Chammartin F, Smith D, Odermatt M, Schuhmacher J, Koller M, Gunthard HF, Briel M, Bucher HC, Speich B; Swiss HIV Cohort Study; Swiss Transplant Cohort Study. Developing and testing a Corona VaccinE tRiAL pLatform (COVERALL) to study Covid-19 vaccine response in immunocompromised patients. BMC Infect Dis. 2022 Jul 28;22(1):654. doi: 10.1186/s12879-022-07621-x.

Reference Type: RESULT

PMID: 35902817 (View on PubMed)

Amstutz A, Chammartin F, Audige A, Eichenberger AL, Braun DL, Amico P, Stoeckle MP, Hasse B, Papadimitriou-Olivgeris M, Manuel O, Bongard C, Schuurmans MM, Hage R, Damm D, Tamm M, Mueller NJ, Rauch A, Gunthard HF, Koller MT, Schonenberger CM, Griessbach A, Labhardt ND, Kouyos RD, Trkola A, Kusejko K, Bucher HC, Abela IA, Briel M, Speich B; Swiss HIV Cohort Study; Swiss Transplant Cohort. Antibody and T-Cell Response to Bivalent Booster SARS-CoV-2 Vaccines in People With Compromised Immune Function: COVERALL-3 Study. J Infect Dis. 2024 Oct 16;230(4):e847-e859. doi: 10.1093/infdis/jiae291.

Reference Type: DERIVED

PMID: 38848312 (View on PubMed)

Griessbach A, Chammartin F, Abela IA, Amico P, Stoeckle MP, Eichenberger AL, Hasse B, Braun DL, Schuurmans MM, Muller TF, Tamm M, Audige A, Mueller NJ, Rauch A, Gunthard HF, Koller MT, Trkola A, Epp S, Amstutz A, Schonenberger CM, Taji Heravi A, Papadimitriou-Olivgeris M, Casutt A, Manuel O, Kusejko K, Bucher HC, Briel M, Speich B; Swiss HIV Cohort Study and the Swiss Transplant Cohort Study. Antibody Response After the Third SARS-CoV-2 Vaccine in Solid Organ Transplant Recipients and People Living With HIV (COVERALL-2). Open Forum Infect Dis. 2023 Nov 3;10(11):ofad536. doi: 10.1093/ofid/ofad536. eCollection 2023 Nov.

Reference Type: DERIVED

PMID: 38023564 (View on PubMed)

Chammartin F, Griessbach A, Kusejko K, Audige A, Epp S, Stoeckle MP, Eichenberger AL, Amstutz A, Schoenenberger CM, Hasse B, Braun DL, Rauch A, Trkola A, Briel M, Bucher HC, Gunthard HF, Speich B, Abela IA; Swiss HIV Cohort Study. Bridging the gap: identifying factors impacting mRNA severe acute respiratory syndrome coronavirus 2 vaccine booster response in people with HIV-1. AIDS. 2024 Feb 1;38(2):217-222. doi: 10.1097/QAD.0000000000003751. Epub 2023 Oct 11.

Reference Type: DERIVED

PMID: 37830908 (View on PubMed)

Chammartin F, Kusejko K, Pasin C, Trkola A, Briel M, Amico P, Stoekle MP, Eichenberger AL, Hasse B, Braun DL, Schuurmans MM, Muller TF, Tamm M, Mueller NJ, Rauch A, Koller MT, Gunthard HF, Bucher HC, Speich B, Abela IA; and the Swiss HIV Cohort Study. Determinants of antibody response to severe acute respiratory syndrome coronavirus 2 mRNA vaccines in people with HIV. AIDS. 2022 Aug 1;36(10):1465-1468. doi: 10.1097/QAD.0000000000003246. Epub 2022 Jul 9.

Reference Type: DERIVED

PMID: 35876706 (View on PubMed)

Speich B, Chammartin F, Smith D, Stoeckle MP, Amico P, Eichenberger AL, Hasse B, Schuurmans MM, Muller T, Tamm M, Dickenmann M, Abela IA, Trkola A, Hirsch HH, Manuel O, Cavassini M, Hemkens LG, Briel M, Mueller NJ, Rauch A, Gunthard HF, Koller MT, Bucher HC, Kusejko K; study groups from the Swiss HIV Cohort Study and the Swiss Transplant Cohort Study. 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(R) and COVID-19 mRNA Vaccine Moderna(R). Trials. 2021 Oct 21;22(1):724. doi: 10.1186/s13063-021-05664-0.

Reference Type: DERIVED

PMID: 34674742 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan: Sub-Protocol

View Document

Document Type: Study Protocol: Master-Protocol

View Document

Document Type: Study Protocol: Second Sub-Protocol

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Document Type: Study Protocol: Third Sub-Protocol

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Other Identifiers

2021-000593; me20Bucher

Identifier Type: -

Identifier Source: org_study_id