Clinical trial NCT04969263: COVID-19 Protection After Transplant Pilot Study
Official title: Immunogenicity of a Third Dose of Either the Moderna COVID-19 Vaccine or Pfizer-BioNTech COVID-19 Vaccine in Kidney Transplant Recipients Who Failed to Respond After Two Previous Doses
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Kidney Transplant Recipients
Keywords: COVID-19 vaccine
SARS-CoV-2 antibody response
Lead sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Sponsor class: NIH
Collaborators: name: PPD Development, LP
First posted: 2021-07-20
Enrollment: 81
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Open label, non-randomized.
Primary purpose: PREVENTION

Brief summary: Antibodies are an important part of the body's defense against infection. Individuals who have no antibodies or very low antibody levels are considered less well protected from Coronavirus Disease 2019 (COVID-19) than those who have higher antibody levels. What level of antibodies is necessary for protection is currently unknown.

Inadequate antibody response to Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) vaccination has been described among kidney transplant recipients. The aim of this study is to elicit an antibody response to vaccination against SARS-CoV-2 in kidney transplant recipients who have failed to respond to two doses of either the Moderna COVID-19 vaccine or Pfizer-BioNTech Coronavirus Disease 2019 (COVID-19) vaccine.

Detailed description: This is an open label, non-randomized study in kidney transplant recipients who received two doses of either mRNA COVID-19 vaccine and have a negative (\<0.8 U/mL) or low (titer \<50 U/mL) SARS-CoV-2 antibody response using the Roche Elecsys® anti-RBD assay. Eligible participants will receive a third dose of the same mRNA vaccine as the prior two doses.

Eligibility criteria: Inclusion Criteria:

Individuals who meet all the following criteria are eligible for enrollment as study participants-

1. Able to understand and provide informed consent;
2. Recipient of kidney transplant ≥12 months prior to enrollment, without treated allograft rejection in the 6 months preceding enrollment;
3. Received 2 doses of either the Moderna COVID-19 vaccine or Pfizer-BioNTech COVID-19 vaccine as specified in the respective Food and Drug Administration Emergency Use Authorization (FDA EUAs), \>30 days and \<8 months prior to enrollment ; and,
4. Negative (antibody titer \< 0.8U/mL) or low (antibodies detected at titer ≤ 50 U/mL) response to the vaccine at \> 30 days from dose 2 of the Moderna COVID-19 vaccine or the Pfizer BioNTech vaccine, using the Roche Elecsys® anti-Receptor Binding Domain (RBD) assay.

Exclusion Criteria:

Individuals who meet any of these criteria are not eligible for enrollment as study participants-

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. Known history of severe allergic reaction to any component of either the Moderna COVID-19 vaccine or Pfizer-BioNTech COVID-19 vaccine;
3. Thrombotic events, myocarditis, or pericarditis temporally associated with prior dose of COVID-19 vaccine;
4. Any change in transplant immunosuppression regimen (drug or dose) in response to suspected or proven rejection within the last 6 months;
5. Significant graft dysfunction;
6. Receipt of any cellular depleting agent (e.g. ATG, Rituximab, Alemtuzumab, Cyclophosphamide) within 12 months preceding enrollment;
7. Receiving systemic immunomodulatory medication(s) for any condition other than transplant;
8. Any untreated active infection, including BK viremia \>10\^4 copies;
9. Infection with human immunodeficiency virus (HIV);
10. Maintenance immunosuppressive regimen that includes belatacept or abatacept;
11. Recent (within one year) or ongoing treatment for malignancy; or
12. Any past or current medical problems, treatments, or findings which, in the opinion of the investigator, may pose additional risks from participation in the study, may interfere with the candidate's ability to comply with study requirements or may impact the quality or interpretation of the data obtained from the study.

Primary outcomes:
measure: Proportion of Recipients Who Achieve an Antibody Response >50 U/mL After the Third Dose of mRNA COVID-19 Vaccine
timeFrame: Outcome was measured at 30 days after study intervention (dose 3 vaccination)
Secondary outcomes:
measure: Frequency of/Proportion of Participants With Vaccine Reactogenicity (Local or Systemic) and/or Allergy to the mRNA-Based COVID-19 Vaccine
timeFrame: Through Day 7 Post-Vaccination (Dose 3)
measure: Frequency of/Proportion of Participants With Any Serious Adverse Events (SAEs) Following the Third Dose of an mRNA Vaccine
timeFrame: Through Day 30 Post-Vaccination (Dose 3)
measure: Proportion of Participants Treated for Acute Cell-Mediated and/or Antibody-Mediated Allograft Rejection (Clinical or Biopsy Proven)
timeFrame: Through Day 60 Post-Vaccination (Dose 3)
measure: Proportion of Participants Who Develop de Novo Donor-Specific Anti-Human Leukocyte Antigens (HLA) Antibody
timeFrame: Through Day 90 Post-Vaccination (Dose 3)
measure: Proportion of Participants With Graft Loss
timeFrame: Through Day 60 Post-Vaccination (Dose 3)
measure: Occurrence of Death Among Participants
timeFrame: Through Day 60 Post-Vaccination (Dose 3)
Other outcomes:
Locations:
city: Baltimore
country: United States
facility: Johns Hopkins Hospital
state: Maryland
Study officials:
affiliation: Department of Surgery, NYU Grossman School of Medicine
name: Dorry L. Segev, MD, PhD
role: STUDY_CHAIR
References:
citation: Werbel WA, Boyarsky BJ, Ou MT, Massie AB, Tobian AAR, Garonzik-Wang JM, Segev DL. Safety and Immunogenicity of a Third Dose of SARS-CoV-2 Vaccine in Solid Organ Transplant Recipients: A Case Series. Ann Intern Med. 2021 Sep;174(9):1330-1332. doi: 10.7326/L21-0282. Epub 2021 Jun 15. No abstract available.