MedPath

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

Phase 2
Active, not recruiting
Conditions
Kidney Transplant
COVID-19
Interventions
Biological: Sanofi-GSK monovalent (B.1.351) CoV2 preS dTM-AS03 COVID-19 vaccine
Registration Number
NCT05518487
Lead Sponsor
National Institute of Allergy and Infectious Diseases (NIAID)
Brief Summary

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

Detailed Description

Not available

Recruitment & Eligibility

Status
ACTIVE_NOT_RECRUITING
Sex
All
Target Recruitment
80
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

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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
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Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
Kidney transplant recipientsSanofi-GSK monovalent (B.1.351) CoV2 preS dTM-AS03 COVID-19 vaccineThis 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)
Primary Outcome Measures
NameTimeMethod
The proportion of participants who reach a SARS-CoV-2 S antibody level >5000 U/mLAt 30 days following a dose of vaccine

The antibody is measured by using the Roche Elecsys(R) anti-RBD assay

Secondary Outcome Measures
NameTimeMethod
Composite that includes death, graft loss, need for dialysis, and acute rejectionWithin 30 days following the study dose of vaccine
Adverse EventsUp to 30 days after 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
Change in pre-existing donor-specific anti-human leukocyte antigens (HLA) antibodyFrom study entry to 90 days post vaccine and up to 12-months post vaccine
Graft lossWithin 30 days and 60 days of the study dose of vaccine
Need for dialysisWithin 30 days and 60 days of the study dose of vaccine
Interquartile range of Monogram pseudovirus antibody titersAt 14 and 30 days after the study vaccine dose

For selected variants of concern (prototype (Wuhan), beta, and omicron BA.1; additional alternative strains to be determined based on assay availability)

DeathWithin 30 days and 60 days of the study dose of vaccine
Acute rejectionWithin 30 days and 60 days of the study dose of vaccine
Solicited local and systemic vaccine reactogenicityCollected for 7 days following the study dose of vaccine)
Serious adverse events1 year following the study dose of vaccine
Interquartile range of fold rise (FR)From baseline to 30 days after the study dose of vaccine

The antibody is measured by using the Roche Elecsys(R) anti-RBD assay

Median range of anti-RBD antibody concentrationAt 30 days after the study dose of vaccine

The antibody is measured by using the Roche Elecsys(R) anti-RBD assay

Interquartile range of anti-RBD antibody concentrationAt 30 days after the study dose of vaccine

The antibody is measured by using the Roche Elecsys(R) anti-RBD assay

Median of fold rise (FR) in anti-RBD antibody concentrationFrom baseline to 30 days after the study dose of vaccine

The antibody is measured by using the Roche Elecsys(R) anti-RBD assay

Interquartile range of fold rise (FR) in Monogram pseudovirus antibody titersfrom baseline to 14 and 30 days after the study vaccine dose

For selected variants of concern (prototype (Wuhan), beta, and omicron BA.1; additional alternative strains to be determined based on assay availability)

Adverse Events of Special Interest (AESIs), including potential immune mediated diseases1 year following the study dose of vaccine
Development of de novo donor-specific anti-human leukocyte antigens (HLA) antibodyWithin 90 days of the vaccine and up to 12-months post vaccine
Median range of Monogram pseudovirus antibody titersAt 14 and 30 days after the study vaccine dose

For selected variants of concern (prototype (Wuhan), beta, and omicron BA.1; additional alternative strains to be determined based on assay availability)

Median range of fold rise (FR) in Monogram pseudovirus antibody titersFrom baseline to 14 and 30 days after the study vaccine dose

For selected variants of concern (prototype (Wuhan), beta, and omicron BA.1; additional alternative strains to be determined based on assay availability)

Trial Locations

Locations (6)

University of California San Diego Medical Center: Transplantation

🇺🇸

San Diego, California, United States

Emory University School of Medicine: Transplantation

🇺🇸

Atlanta, Georgia, United States

UCSF School of Medicine: Transplantation

🇺🇸

San Francisco, California, United States

Johns Hopkins Institute for Clinical and Translational Research: Broadway Adult Outpatient Clinical Research Unit

🇺🇸

Baltimore, Maryland, United States

University of Illinois Medical Center: Transplantation

🇺🇸

Chicago, Illinois, United States

University of Wisconsin School of Medicine and Public Health: Transplantation

🇺🇸

Madison, Wisconsin, United States

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