Immunocompromised Swiss Cohorts Based Trial Platform

NCT04805125 | Completed Phase 3 DMC

• 1 other identifier: 2021-000593; me20Bucher
• Study Type: interventional
• Target: 610
• Locations: 1 country
• Sites: 4

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.

Conditions

Immunocompromised Patients

Keywords

Covid-19 infection; SARS-CoV-2-specific antibodies; Sars-CoV-2 vaccine; vector based messenger ribonucleic acid (mRNA) vaccines; SARS-CoV-2 infection; Swiss HIV Cohort Study [SHCS]; Swiss Transplant Cohort Study [STCS]; BNT162b2; mRNA-1273; bivalent SARS-CoV-2 vaccine; mRNA-1273.214

Outcome Measures

Primary Outcomes (16)

• immunological outcome: change in pan-Ig antibody response (pan-Ig anti-S1-RBD)

  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.

  at baseline (day of vaccination) and three months after vaccination

• immunological outcome: change in anti-Nucleocapsid (N) response

  Qualitative measurement of anti-Nucleocapsid (N) responses with Elecsys® Anti-SARS-CoV-2 N assay

  at baseline (day of vaccination) and three months after vaccination

• immunological outcome: change in SARS-CoV-2-binding antibodies

  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.

  at baseline (day of vaccination) and three months after vaccination

• Number of participants with newly polymerase chain reaction (PCR)-confirmed asymptomatic COVID-19 infection

  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 \[(i.e. fever or chills, cough, shortness of breath or difficulty breathing, fatigue, muscle or body aches, headache, new loss of taste or smell, sore throat, congestion or runny nose nausea or vomiting, and diarrhea\])

  at any time point in within 48 weeks following randomisation (day of vaccination)

• Number of participants with newly PCR-confirmed symptomatic COVID-19 infection

  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

  at any time point in within 48 weeks following randomisation (day of vaccination)

• Number of participants with severe COVID-19 infection

  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

  at any time point in within 48 weeks following randomisation (day of vaccination)

• Clinical Outcome: COVID-19 burden of diseases (BOD)

  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.

  within 48 weeks following randomisation (day of vaccination)

• Duration of RCT set up (specific endpoint related to trial conduct feasibility)

  Duration of RCT set up (i.e. time from deciding which interventions will be tested until the first patient is randomised).

  one time assessment at baseline (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 of patient recruitment from activation of first study site until 40 patients are randomised

  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 380 patients are randomised

  Time of patient recruitment from activation of first study site until 380 patients are randomised

  one time assessment after approx. 3 months (from activation of first study site until 380 patients are randomised)

• Patient consent rate

  Patient consent rate (i.e. proportion of patients giving informed consent out of approached eligible patients)

  approx. 3 months

• Proportion of missing data for all baseline variables from routinely collected cohort data

  Proportion of missing data for all baseline variables from routinely collected cohort data

  one time assessment at baseline

• Proportion of missing data for all clinical outcomes

  Proportion of missing data for all clinical outcomes from routinely collected cohort data and outcome data that is collected in the trial platform

  one time assessment after approx. 3 months

• SARS-CoV-2-specific antibodies

  SARS-CoV-2-specific antibodies (using a pan-IgG antibody assay against the receptor binding domain (RBD) against the nP and spike 1 subunits)

  three months after vaccination

• SARS-CoV-2-specific titers

  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)

  three months after vaccination

• The proportion of patients with a positive antibody response to SARS-CoV-2 spike (S1) protein receptor binding domain in human serum or plasma assessed in the observational second sub- protocol

  The proportion of patients with a positive antibody response to SARS-CoV-2 spike (S1) protein receptor binding domain in human serum or plasma assessed or plasma assessed in the observational second sub- protocol by the commercial immunoassay Elecsys Anti-SARS-CoV-2 S (Elecsys S) from Roche Diagnostics. An antibody response will be considered as positive using the threshold ≥ 100 units/ml, predicting a protective immune response.

  8 weeks (¨+/- 2 weeks) after 3. vaccination

Secondary Outcomes (6)

• The proportion of patients with a positive antibody response using SARS-CoV-2 spike (S1) Elecsys S by Roche in the observational second sub- protocol, using a threshold of ≥0.8 units/ml as defined by the manufacturer

  8 weeks (¨+/- 2 weeks) after 3. vaccination

• The proportion of patients with a positive antibody response using antibody response using the Antibody CORonavirus Assay (ABCORA) 2 in the observational second sub- protocol

  8 weeks (¨+/- 2 weeks) after 3. vaccination

• The proportion of patients with neutralizing neutralization activity against the vaccine strain Wuhan-Hu-1 in the observational second sub- protocol

  8 weeks (¨+/- 2 weeks) after 3. vaccination

• Immune response (pan-Ig antibodies against the receptor binding domain (RBD) in the S1 subunit of the spike protein (pan-Ig anti-S1-RBD) of SARS-CoV-2 in the observational second sub- protocol

  8 weeks (¨+/- 2 weeks) after 3. vaccination

• Mean immune response of IgM, IgA and IgG to the subunit S1 using ABCORA in the observational second sub- protocol

  8 weeks (¨+/- 2 weeks) after 3. vaccination

Other Outcomes (7)

• Safety Outcome: number of local symptoms

  during the first 7 days after vaccination

• Safety Outcome: number of systemic symptoms

  during the first 7 days after vaccination

• Safety Outcome: number of vaccine related symptoms

  during the first 7 days after vaccination

Study Arms (2)

Moderna mRNA COVID-19 vaccine

ACTIVE COMPARATOR

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

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

Comirnaty® (Pfizer / BioNTech) mRNA COVID-19 vaccine

ACTIVE COMPARATOR

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

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

Interventions

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

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

Moderna mRNA COVID-19 vaccine

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

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

Comirnaty® (Pfizer / BioNTech) mRNA COVID-19 vaccine

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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:
• 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

Sponsors & Collaborators

• University Hospital, Basel, Switzerland: lead
• Swiss National Science Foundation: collaborator
• ModernaTX, Inc.: collaborator

Study Sites (4)

University Hospital Basel

Basel, 4031, Switzerland

Location

University Hospital Bern

Bern, 3010, Switzerland

Location

University Hospital Lausanne CHUV

Lausanne, 1011, Switzerland

Location

University Hospital Zurich

Zurich, 8091, Switzerland

Location

Related Publications (7)

• 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.

  PMID: 35234868 RESULT

• 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.

  PMID: 35902817 RESULT

• 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.

  PMID: 38848312 DERIVED

• 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.

  PMID: 38023564 DERIVED

• 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.

  PMID: 37830908 DERIVED

• 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.

  PMID: 35876706 DERIVED

• 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.

  PMID: 34674742 DERIVED

MeSH Terms

Conditions

COVID-19

Interventions

2019-nCoV Vaccine mRNA-1273; BNT162 Vaccine

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

mRNA Vaccines; Nucleic Acid-Based Vaccines; Vaccines, Synthetic; Recombinant Proteins; Proteins; Amino Acids, Peptides, and Proteins; Vaccines; Biological Products; Complex Mixtures; COVID-19 Vaccines; Viral Vaccines; Antigens; Biological Factors

Study Officials

• Heiner C. Bucher, Prof. Dr. med.

  Basel Institute for Clinical Epidemiology & Biostatistics, University Hospital Basel

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Cohort embedded platform with a first sub-study pilot trial of two arms comparing licensed vaccines against SARS-CoV-2. The platform design allows to expand the pilot trial into a larger trial by sub-protocols to add or drop vaccine arms or to add further sub-protocols for re-randomization of patients with no immune response to a vaccine booster or new vaccines A parallel two-arm open-label randomized controlled exploratory pilot trial comparing the first in Switzerland approved SARS-CoV-2 vaccines (based on a trial platform that is integrated into the ongoing routine prospective data collection of two national cohorts, the SHCS and STCS). Within substudy-2 and substudy-3 observational studies were added to the platform trial.

Study Record Dates

• First Submitted: March 15, 2021
• First Posted: March 18, 2021
• Study Start: April 19, 2021
• Primary Completion: September 23, 2023
• Study Completion: September 23, 2023
• Last Updated: January 25, 2024

Record last verified: 2024-01

Locations

CH (4)