COVID-19 Protection After Transplant Pilot Study

NCT04969263 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: DAIT COVID19-TB-02NIAID CRMS ID#: 38865
• Study Type: interventional
• Target: 81
• Locations: 1 country
• Sites: 1

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.

Conditions

Kidney Transplant Recipients

Keywords

COVID-19 vaccine; SARS-CoV-2 antibody response

Outcome Measures

Primary Outcomes (1)

• Proportion of Recipients Who Achieve an Antibody Response >50 U/mL After the Third Dose of mRNA COVID-19 Vaccine

  The proportion of participants who achieve an antibody response \>50 U/mL after the third dose of vaccine using the Roche Elecsys® anti-RBD assay is considered to show positive response to the intervention, negative response otherwise.

  Outcome was measured at 30 days after study intervention (dose 3 vaccination)

Secondary Outcomes (6)

• Frequency of/Proportion of Participants With Vaccine Reactogenicity (Local or Systemic) and/or Allergy to the mRNA-Based COVID-19 Vaccine

  Through Day 7 Post-Vaccination (Dose 3)

• Frequency of/Proportion of Participants With Any Serious Adverse Events (SAEs) Following the Third Dose of an mRNA Vaccine

  Through Day 30 Post-Vaccination (Dose 3)

• Proportion of Participants Treated for Acute Cell-Mediated and/or Antibody-Mediated Allograft Rejection (Clinical or Biopsy Proven)

  Through Day 60 Post-Vaccination (Dose 3)

• Proportion of Participants Who Develop de Novo Donor-Specific Anti-Human Leukocyte Antigens (HLA) Antibody

  Through Day 90 Post-Vaccination (Dose 3)

• Proportion of Participants With Graft Loss

  Through Day 60 Post-Vaccination (Dose 3)

Study Arms (2)

BNT162b2 mRNA-based vaccine (Pfizer/BioNTech)

EXPERIMENTAL

The BNT162b2 mRNA-based vaccine was developed to prevent COVID-19, the disease resulting from Severe Acute Respiratory Syndrome coronavirus (SARS-CoV-2) infection. Kidney transplant recipients who had a suboptimal antibody response to the standard two doses of vaccination with Pfizer/BioNTech will receive a third dose of the the same vaccine. Administration: One dose administered intramuscularly, upper arm.

Biological: BNT162b2 vaccine (Pfizer/BioNTech)

mRNA-1273 vaccine (Moderna)

EXPERIMENTAL

The mRNA-1273 vaccine was developed to prevent COVID-19, the disease resulting from Severe Acute Respiratory Syndrome coronavirus (SARS-CoV-2) infection. Kidney transplant recipients who had a suboptimal antibody response to the standard two doses of vaccination with Moderna will receive a third dose of the same vaccine. Administration: One dose administered intramuscularly, upper arm.

Biological: mRNA-1273 vaccine (Moderna)

Interventions

BNT162b2 vaccine (Pfizer/BioNTech) BIOLOGICAL

30 microgram dose

Also known as: COMIRNATY (COVID-19 vaccine, mRNA), SARS-CoV-2 mRNA vaccine, Pfizer-BioNTech COVID-19 vaccine

BNT162b2 mRNA-based vaccine (Pfizer/BioNTech)

mRNA-1273 vaccine (Moderna) BIOLOGICAL

100 microgram dose

Also known as: SARS-CoV-2 mRNA vaccine, Moderna COVID-19 vaccine, SPIKEVAX (COVID-19 vaccine, mRNA)

mRNA-1273 vaccine (Moderna)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Individuals who meet all the following criteria are eligible for enrollment as study participants-
• Able to understand and provide informed consent;
• Recipient of kidney transplant ≥12 months prior to enrollment, without treated allograft rejection in the 6 months preceding enrollment;
• 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,
• 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.

You may not qualify if:

• Individuals who meet any of these criteria are not eligible for enrollment as study participants-
• 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;
• Known history of severe allergic reaction to any component of either the Moderna COVID-19 vaccine or Pfizer-BioNTech COVID-19 vaccine;
• Thrombotic events, myocarditis, or pericarditis temporally associated with prior dose of COVID-19 vaccine;
• Any change in transplant immunosuppression regimen (drug or dose) in response to suspected or proven rejection within the last 6 months;
• Significant graft dysfunction;
• Receipt of any cellular depleting agent (e.g. ATG, Rituximab, Alemtuzumab, Cyclophosphamide) within 12 months preceding enrollment;
• Receiving systemic immunomodulatory medication(s) for any condition other than transplant;
• Any untreated active infection, including BK viremia \>10\^4 copies;
• Infection with human immunodeficiency virus (HIV);
• Maintenance immunosuppressive regimen that includes belatacept or abatacept;
• Recent (within one year) or ongoing treatment for malignancy; or
• 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.

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead
• PPD Development, LP: collaborator

Study Sites (1)

Johns Hopkins Hospital

Baltimore, Maryland, 21287, United States

Location

Related Publications (3)

• 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.

  PMID: 34125572 BACKGROUND

• Karaba AH, Morgenlander WR, Johnston TS, Hage C, Pekosz A, Durand CM, Segev DL, Robien MA, Heeger PS, Larsen CP, Blankson JN, Werbel WA, Larman HB, Tobian AAR. Epitope Mapping of SARS-CoV-2 Spike Antibodies in Vaccinated Kidney Transplant Recipients Reveals Poor Spike Coverage Compared to Healthy Controls. J Infect Dis. 2024 May 15;229(5):1366-1371. doi: 10.1093/infdis/jiad534.

  PMID: 38019656 DERIVED

• Werbel WA, Karaba AH, Chiang TP, Massie AB, Brown DM, Watson N, Chahoud M, Thompson EA, Johnson AC, Avery RK, Cochran WV, Warren D, Liang T, Fribourg M, Huerta C, Samaha H, Klein SL, Bettinotti MP, Clarke WA, Sitaras I, Rouphael N, Cox AL, Bailey JR, Pekosz A, Tobian AAR, Durand CM, Bridges ND, Larsen CP, Heeger PS, Segev DL; CPAT investigators. Persistent SARS-CoV-2-specific immune defects in kidney transplant recipients following third mRNA vaccine dose. Am J Transplant. 2023 Jun;23(6):744-758. doi: 10.1016/j.ajt.2023.03.014. Epub 2023 Mar 24.

  PMID: 36966905 DERIVED

MeSH Terms

Interventions

BNT162 Vaccine; COVID-19 Vaccines; RNA, Messenger; CVnCoV COVID-19 vaccine; 2019-nCoV Vaccine mRNA-1273

Intervention Hierarchy (Ancestors)

mRNA Vaccines; Nucleic Acid-Based Vaccines; Vaccines, Synthetic; Recombinant Proteins; Proteins; Amino Acids, Peptides, and Proteins; Vaccines; Biological Products; Complex Mixtures; Viral Vaccines; Antigens; Biological Factors; RNA; Nucleic Acids; Nucleic Acids, Nucleotides, and Nucleosides

Results Point of Contact

• Title: Director, Clinical Research Operations Program
• Organization: DAIT/NIAID

DAITClinicalTrialsGov@niaid.nih.gov

301-594-7669

Study Officials

• Dorry L. Segev, MD, PhD

  Department of Surgery, NYU Grossman School of Medicine

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Model Details: Open label, non-randomized.

Study Record Dates

• First Submitted: July 16, 2021
• First Posted: July 20, 2021
• Study Start: August 10, 2021
• Primary Completion: November 10, 2022
• Study Completion: March 10, 2023
• Last Updated: July 30, 2025
• Results First Posted: January 22, 2024

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will share
• Time Frame: On average, within 24 months after database lock for the trial.
• Access Criteria: Open access.

Locations

US (1)