Booster Dose of COVID-19 Vaccine for Kidney Transplant Recipients Without Adequate Humoral Response

NCT04961229 | Unknown Phase 4 DMC FDA Drug

• 1 other identifier: 0192-21-RMC
• Study Type: interventional
• Target: 504
• Locations: 0 countries
• Sites: N/A

Brief Summary

Introduction: Inadequate antibody response to mRNA SARS-CoV-2 vaccination has been described among kidney transplant recipients. Immunosuppression level and specifically, use of antimetabolite in the maintenance immunosuppressive regimen, are associated with inadequate response. In light of the severe consequences of COVID-19 in solid organ transplant recipients, we believe it is justified to examine new vaccination strategies in these patients. Methods and analysis: BECAME is a single center, open label, investigator-initiated randomised controlled, superiority trial, aiming to compare immunosuppression reduction combined with a third BNT162b2 vaccine dose versus third dose alone. The primary outcome will be seropositivity rate against SARS-CoV-2. A sample size of 154 patients was calculated for the seropositivity endpoint assuming 25% seropositivity in the control group and 50% in the intervention group. A sample of participant per arm will be also teste for T-cell response. We also plan to perform a prospective observational study, evaluating seropositivity among \~350 kidney transplant recipients consenting to receive a third vaccine dose, who are not eligible for the randomised controlled trial. Ethics and dissemination: The trial is approved by local ethics committee of Rabin medical center (RMC-0192- 21). Results of this trial will be published; trial data will be available. Protocol amendments will be submitted to the local ethics committee.

Conditions

COVID-19 Acute Respiratory Distress Syndrome; Immunosuppression

Keywords

kidney transplant recipients; COVID-19; vaccine; immunosuppression reduction; randomized controlled trial

Outcome Measures

Primary Outcomes (1)

• anti-spike protein titer above 50 AU/ml 2 weeks post vaccination

  positive humoral response against SARS-CoV-2

  2 weeks post vaccination

Secondary Outcomes (7)

• anti-spike protein titer above 50 AU/ml 3-, 6-, and 12-months post vaccination

  3-, 6-, and 12-months post vaccination

• Log transformed titer of anti-spike protein weeks and 3, 6, and 12 months post vaccination

  2 weeks and 3, 6, and 12 months post vaccination

• Adverse events to booster dose using CTCAE v4.0 criteria

  2 weeks post vaccine

• Acute rejection of the allograft either documented by biopsy or clinically suspected, defined as increase in creatinine by 20% from baseline, without any other plausible explanation

  2 weeks, 3,6, and 12 months post vaccination

• positive PCR test to SARS-CoV-2 during the follow up period

  until 12 months following vaccine

Study Arms (3)

Third dose of BNT162b2 vaccine with Immunosuppression reduction

EXPERIMENTAL

Third dose of BNT162b2 vaccine with reduction of mycophenolic acid dose

Biological: The Pfizer mRNA-based BNT162b2 vaccine

Third dose of BNT162b2 vaccine without immunosuppression reduction

EXPERIMENTAL

Third dose of BNT162b2 vaccine without reduction of mycophenolic acid dose

Biological: The Pfizer mRNA-based BNT162b2 vaccine

Third dose of BNT162b2 vaccine

EXPERIMENTAL

Third dose of BNT162b2 vaccine with no change in immunosuppression for patients that are excluded from the randomised trial

Biological: The Pfizer mRNA-based BNT162b2 vaccine

Interventions

The Pfizer mRNA-based BNT162b2 vaccine BIOLOGICAL

participants who gave informed consent to participate in either the prospective non-randomised study or RCT will receive a single vaccine dose. In addition, participants in the RCT will be randomised into two groups: 1. Third booster dose of BNT162b2 (one standard dose) with no change in immunosuppression protocol 2. Third booster dose of BNT162b2 (one standard dose) with immunosuppression reduction according to protocol (mycophenolic temporary cessation 4 days before (5 half-lives) and one week (expected antibody response) after vaccination (to allow for antibody response).

Third dose of BNT162b2 vaccine; Third dose of BNT162b2 vaccine with Immunosuppression reduction; Third dose of BNT162b2 vaccine without immunosuppression reduction

Eligibility Criteria

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

You may qualify if:

• kidney transplant recipients that received two doses of BNT162b2 vaccine at least 3 weeks prior to enrollment, and were seronegative (IgG against the spike protein of SARS-CoV-2 below 50 AU/ml) at least two weeks after the second vaccine dose
• Recipients treated by three anti-rejection medications including: prednisone, tacrolimus, mycophenolate mofetil or mycophenolic acid.

You may not qualify if:

• Past infection with SARS-CoV-2
• Pregnancy
• Age below 18 years
• Active infection
• \- Recipients at a high risk for acute or chronic humoral rejection including:
• Recipients with positive panel-reactive antibody (PRA) (any positive value) at any time before or after transplantation
• Recipients that had an acute rejection in the last year
• Recipients less than 6 months after transplantation
• Recipients that are considered at high risk for rejection according to the primary care nephrologist
• Recipients taking less than 3 anti-rejection medications
• Recipients currently treated with mTOR inhibitors (everolimus, sirolimus) and/or azathioprine
• Recipients treated with plasmapheresis in the previous 3 months
• Recipients treated with eculizumab in the last year
• Recipient treated with IVIG in the previous 3 months
• Recipient treated with rituximab in the previous 6 months

Sponsors & Collaborators

• dafna yahav: lead

Related Publications (1)

• Yahav D, Rozen-Zvi B, Mashraki T, Atamna A, Ben-Zvi H, Bar-Haim E, Rahamimov R. Immunosuppression reduction when administering a booster dose of the BNT162b2 mRNA SARS-CoV-2 vaccine in kidney transplant recipients without adequate humoral response following two vaccine doses: protocol for a randomised controlled trial (BECAME study). BMJ Open. 2021 Oct 11;11(10):e055611. doi: 10.1136/bmjopen-2021-055611.

  PMID: 34635537 DERIVED

MeSH Terms

Conditions

COVID-19

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Ruth Rahaminov

  Rabin Medical Center, Beilinson Campus, Petah-Tikva, Israel

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Ruth Rahaminov

CONTACT

97239376475; rutir@clalit.org.il

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Clinical Professor, Infectious Diseases Unit, Rabin Medical Center, Beilinson Campus, Petah-Tikva, Israel

Study Record Dates

• First Submitted: July 13, 2021
• First Posted: July 14, 2021
• Study Start: October 1, 2021
• Primary Completion: February 1, 2022
• Study Completion: July 1, 2022
• Last Updated: October 8, 2021

Record last verified: 2021-10

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, ICF
• Time Frame: The data will become available once entered for all patients and analyzed, presumably at 1-January-2022. It will be available for one year.
• Access Criteria: Researchers who would like to share the data will be requested to send the PI their protocol/reason for asking the data. After reviewing the request, if the protocol seems adequate in terms of clinical question and methodological quality, we will share anonymized data.