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

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)

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

Study Overview

• Status: Active, not recruiting
• Conditions: COVID-19; Kidney Transplant
• Intervention / Treatment: Biological: Sanofi-GSK monovalent (B.1.351) CoV2 preS dTM-AS03 COVID-19 vaccine

• Study Type: Interventional
• Enrollment (Estimated): 80
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • San Diego, California, United States, 92093
      • University of California San Diego Medical Center: Transplantation
    • San Francisco, California, United States, 94143
      • UCSF School of Medicine: Transplantation
  • Georgia
    • Atlanta, Georgia, United States, 30332
      • Emory University School of Medicine: Transplantation
  • Illinois
    • Chicago, Illinois, United States, 60612
      • University of Illinois Medical Center: Transplantation
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Johns Hopkins Institute for Clinical and Translational Research: Broadway Adult Outpatient Clinical Research Unit
  • Wisconsin
    • Madison, Wisconsin, United States, 53706
      • University of Wisconsin School of Medicine and Public Health: Transplantation

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Able to understand and provide informed consent
2. Individual ≥ 18 years of age.
3. Recipient of kidney transplant >=12 months prior to enrollment, without treated allograft rejection in the 6 months preceding enrollment
4. Maintenance immunosuppressive regimen consisting of CNI and mycophenolate mofetil or mycophenolate, with or without <= 5mg/day prednisone or equivalent
5. 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
6. Receipt a COVID-19 bivalent mRNA booster (Moderna or Pfizer-BioNTech) >30 days prior to enrollment.
7. 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
8. 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)

9. A female participant is eligible to participate if she is not pregnant or breastfeeding and one of the following conditions applies:

   1. 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

   2. 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:

1. 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
2. Recipient of any organ other than a kidney
3. Known current or prior Donor Specific Antibody (DSA)
4. Any change in transplant immunosuppression regimen (drug or dose) in response to suspected or proven rejection within the last 6 months
5. Known diagnosis of COVID-19 since last antibody test
6. Receipt of a monoclonal antibody product or convalescent plasma within the last 30 days
7. 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)
8. Bleeding disorder, or receipt of anticoagulants in the past 21 days preceding inclusion, contraindicating intramuscular (IM) vaccination based on Investigator's judgment
9. 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
10. Receipt of any vaccine in the 30 days preceding the study vaccine or planned vaccines in the 30 days following the study vaccine
11. Estimated Glomerular Filtration Rate <30mL/min/1.73m^2
12. Receipt of any cellular depleting agent (e.g. Antithymocyte globulin (ATG), Rituximab, Alemtuzumab, Cyclophosphamide) within 12 months preceding enrollment
13. Receiving systemic immunomodulatory medication(s) for any condition other than transplant
14. Any uncontrolled active infection
15. Infection with human immunodeficiency virus (HIV)
16. Maintenance immunosuppressive regimen that includes anything other than a CNI, mycophenolate/mycophenolate mofetil, and =< 5mg/day prednisone or equivalent
17. Recent (within one year) or ongoing treatment for malignancy, except for definitive surgical treatment of localized skin cancers
18. 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Kidney transplant recipients; 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; 0.5 mL per dose of the Sanofi-GSK COVID-19 Vaccine will be administered intramuscularly in the deltoid muscle of the upper arm

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
• Collaborators: Johns Hopkins University; PPD; Sanofi Pasteur, a Sanofi Company
• Investigators: Principal Investigator: Christine Durand, MD, Johns Hopkins University; Study Chair: Dorry Segev, MD, Ph.D., New York University Langone Health-Transplantation; Study Chair: Peter S Heeger, MD, Icahn School of Medicine at Mount Sinai: Transplantation; Study Chair: Christian P. Larsen, MD, D.Phil., Emory University School of Medicine: Transplantation; Study Chair: William A. Werbel, MD, Johns Hopkins University

Publications and helpful links

Helpful Links

• National Institute of Allergy and Infectious Diseases (NIAID)

Study record dates

Study Major Dates

• Study Start (Actual): February 20, 2023
• Primary Completion (Actual): February 28, 2024
• Study Completion (Estimated): July 1, 2025

Study Registration Dates

• First Submitted: August 18, 2022
• First Submitted That Met QC Criteria: August 24, 2022
• First Posted (Actual): August 26, 2022

Study Record Updates

• Last Update Posted (Actual): April 4, 2024
• Last Update Submitted That Met QC Criteria: April 3, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: Vaccine; COVID-19; Kidney transplant
• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19
• Other Study ID Numbers: DAIT COVID19-TB-04

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: The plan is to share data upon completion of the study in: Immunology Database and Analysis Portal (ImmPort), a long-term archive of clinical and mechanistic data from DAIT-funded grants and contracts.
• IPD Sharing Time Frame: On average, within 24 months after database lock for the trial.
• IPD Sharing Access Criteria: Open access.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No