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

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

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