COVID Protection After Transplant - Sanofi GSK (CPAT-SG) Study

Study Overview
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Brief Summary
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An open label, non-randomized pilot study in kidney transplant recipients who received a completed primary series and bivalent booster of mRNA based COVID-19 vaccine and have =<2500 U/mL SARS-CoV-2 S antibody concentration using the Roche Elecsys(R) anti-RBD assay. Up to 80 participants will be enrolled in this study. Eligible participants will receive a dose of the Sanofi-GSK monovalent (B.1.351) CoV2 preS dTM-AS03 COVID-19 vaccine candidate.. The primary objective is to determine whether a booster dose of the Sanofi-GSK monovalent (B.1.351) CoV2 preS dTM-AS03 COVID-19 vaccine will elicit an increased SARS-CoV-2 antibody response in participants who have failed to maintain an antibody titer >2500 U/mL (using the Roche Elecsys(R) anti-RBD assay) to 2 or more doses of mRNA based COVID-19 vaccine

Official Title
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Safety and Immunogenicity of a Dose of the Sanofi-GSK Monovalent (B.1.351) CoV2 preS dTM-AS03 COVID-19 Vaccine in Kidney Transplant Recipients With a Persistently Low SARS CoV-2 Antibody Titer (COVID19-TB-04)

Conditions
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COVID-19, Kidney Transplant

Intervention / Treatment
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* Biological: Sanofi-GSK monovalent (B.1.351) CoV2 preS dTM-AS03 COVID-19 vaccine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Able to understand and provide informed consent Individual ≥ 18 years of age. Recipient of kidney transplant >=12 months prior to enrollment, without treated allograft rejection in the 6 months preceding enrollment Maintenance immunosuppressive regimen consisting of CNI and mycophenolate mofetil or mycophenolate, with or without <= 5mg/day prednisone or equivalent Received completed primary series (3 doses) of mRNA vaccine (either the Moderna COVID-19 vaccine or Pfizer-BioNTech COVID-19 vaccine) as specified in the respective package inserts Receipt a COVID-19 bivalent mRNA booster (Moderna or Pfizer-BioNTech) >30 days prior to enrollment. Serum antibody titer up to 2500 U/mL at >=30 days from the last dose of mRNA COVID-19 vaccine and =>30 days following receipt of a monoclonal antibody product or convalescent plasma for COVID-19, measured using the Roche Elecsys(R) anti-SARS-CoV-2 S assay Platelet count greater than 30,000/cu mm must be confirmed in participants with a known history of bleeding disorder or thrombocytopenia (platelet count <50,000/cu mm) A female participant is eligible to participate if she is not pregnant or breastfeeding and one of the following conditions applies: Is of non-childbearing potential. To be considered of non-childbearing potential, a female must be post-menopausal for at least 1 year or surgically sterile OR Is of childbearing potential and agrees to use an effective contraceptive method or abstinence for 12 weeks post vaccine and while taking mycophenolate mofetil/mycophenolic acid Exclusion Criteria: Recipient of any number of doses of any COVID vaccine product other than the Moderna COVID-19 vaccine or the Pfizer-BioNTech COVID-19 vaccine Recipient of any organ other than a kidney Known current or prior Donor Specific Antibody (DSA) Any change in transplant immunosuppression regimen (drug or dose) in response to suspected or proven rejection within the last 6 months Known diagnosis of COVID-19 since last antibody test Receipt of a monoclonal antibody product or convalescent plasma within the last 30 days Known history of hypersensitivity to any of the vaccine components, or history of a life-threatening reaction to a vaccine containing any of the same substances. (components listed in Section 6, and the CoV2 and AS03 Investigator's Brochure) Bleeding disorder, or receipt of anticoagulants in the past 21 days preceding inclusion, contraindicating intramuscular (IM) vaccination based on Investigator's judgment Moderate or severe acute illness/infection (according to investigator judgment) on the day of vaccination or febrile illness (temperature >=38.0°C [>=100.4°F]). A prospective participant should not be included in the study until the condition has resolved or the febrile event has subsided Receipt of any vaccine in the 30 days preceding the study vaccine or planned vaccines in the 30 days following the study vaccine Estimated Glomerular Filtration Rate <30mL/min/1.73m^2 Receipt of any cellular depleting agent (e.g. Antithymocyte globulin (ATG), Rituximab, Alemtuzumab, Cyclophosphamide) within 12 months preceding enrollment Receiving systemic immunomodulatory medication(s) for any condition other than transplant Any uncontrolled active infection Infection with human immunodeficiency virus (HIV) Maintenance immunosuppressive regimen that includes anything other than a CNI, mycophenolate/mycophenolate mofetil, and =< 5mg/day prednisone or equivalent Recent (within one year) or ongoing treatment for malignancy, except for definitive surgical treatment of localized skin cancers Any unstable acute or chronic illness, treatments, or findings which, in the opinion of the investigator, may pose additional risks from participation in the study, may interfere with the c candidate's ability to comply with study requirements or may impact the quality or interpretation of the data obtained from the study

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Kidney transplant recipients<br>This single-arm trial will administer a single dose of the Sanofi-GSK monovalent (B.1.351) CoV2 preS dTM-AS03 COVID-19 vaccine to kidney transplant recipients who demonstrate a persistently low (=< 2500 u/mL) anti-spike antibody response after completion of primary series and bivalent booster of either the Moderna COVID-19 Vaccine or the Pfizer-BioNTech Vaccine, as described in their respective Food and Drug Administration (FDA) Emergency Use Authorizations (EUAs) | Biological: Sanofi-GSK monovalent (B.1.351) CoV2 preS dTM-AS03 COVID-19 vaccine<br>* 0.5 mL per dose of the Sanofi-GSK COVID-19 Vaccine will be administered intramuscularly in the deltoid muscle of the upper arm<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The proportion of participants who reach a SARS-CoV-2 S antibody level >5000 U/mL | The antibody is measured by using the Roche Elecsys(R) anti-RBD assay | At 30 days following a dose of vaccine | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Composite that includes death, graft loss, need for dialysis, and acute rejection |  | Within 30 days following the study dose of vaccine | 
| Death |  | Within 30 days and 60 days of the study dose of vaccine | 
| Graft loss |  | Within 30 days and 60 days of the study dose of vaccine | 
| Need for dialysis |  | Within 30 days and 60 days of the study dose of vaccine | 
| Acute rejection |  | Within 30 days and 60 days of the study dose of vaccine | 
| Solicited local and systemic vaccine reactogenicity |  | Collected for 7 days following the study dose of vaccine) | 
| Adverse Events |  | Up to 30 days after the study dose of vaccine | 
| Serious adverse events |  | 1 year following the study dose of vaccine | 
| Adverse Events of Special Interest (AESIs), including potential immune mediated diseases |  | 1 year following the study dose of vaccine | 
| Treated acute cell-mediated allograft rejection (clinical or biopsy-proven) |  | Within 60 days following the study dose of vaccine | 
| Treated antibody-mediated allograft rejection (clinical or biopsy-proven) |  | Within 60 days following the study dose of vaccine | 
| Development of de novo donor-specific anti-human leukocyte antigens (HLA) antibody |  | Within 90 days of the vaccine and up to 12-months post vaccine | 
| Change in pre-existing donor-specific anti-human leukocyte antigens (HLA) antibody |  | From study entry to 90 days post vaccine and up to 12-months post vaccine | 
| Median range of anti-RBD antibody concentration | The antibody is measured by using the Roche Elecsys(R) anti-RBD assay | At 30 days after the study dose of vaccine | 
| Interquartile range of anti-RBD antibody concentration | The antibody is measured by using the Roche Elecsys(R) anti-RBD assay | At 30 days after the study dose of vaccine | 
| Median of fold rise (FR) in anti-RBD antibody concentration | The antibody is measured by using the Roche Elecsys(R) anti-RBD assay | From baseline to 30 days after the study dose of vaccine | 
| Interquartile range of fold rise (FR) | The antibody is measured by using the Roche Elecsys(R) anti-RBD assay | From baseline to 30 days after the study dose of vaccine | 
| Median range of Monogram pseudovirus antibody titers | For selected variants of concern (prototype (Wuhan), beta, and omicron BA.1; additional alternative strains to be determined based on assay availability) | At 14 and 30 days after the study vaccine dose | 
| Interquartile range of Monogram pseudovirus antibody titers | For selected variants of concern (prototype (Wuhan), beta, and omicron BA.1; additional alternative strains to be determined based on assay availability) | At 14 and 30 days after the study vaccine dose | 
| Median range of fold rise (FR) in Monogram pseudovirus antibody titers | For selected variants of concern (prototype (Wuhan), beta, and omicron BA.1; additional alternative strains to be determined based on assay availability) | From baseline to 14 and 30 days after the study vaccine dose | 
| Interquartile range of fold rise (FR) in Monogram pseudovirus antibody titers | For selected variants of concern (prototype (Wuhan), beta, and omicron BA.1; additional alternative strains to be determined based on assay availability) | from baseline to 14 and 30 days after the study vaccine dose | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Vaccine, Kidney transplant, COVID-19