Booster Dose of mRNA SARS-CoV-2 Vaccine for Kidney Transplant Recipients Without Adequate Humoral Response With or Without Immunosuppression Reduction

• ClinicalTrials.gov Identifier: NCT04961229
• Recruitment Status: Not yet recruiting
• First Posted: July 14, 2021
• Last Update Posted: July 14, 2021
• Sponsor: dafna yahav
• Information provided by (Responsible Party): dafna yahav, Rabin Medical Center

Study Description

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 ~500 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.

Condition or disease	Intervention/treatment	Phase
Vaccines; COVID-19; Immunosuppression; Organ Transplants	Biological: The Pfizer mRNA-based BNT162b2 vaccine	Phase 4

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 450 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Prevention
• Official Title: Booster Dose of mRNA SARS-CoV-2 Vaccine for Kidney Transplant Recipients Without Adequate Humoral Response With or Without Immunosuppression Reduction - Protocol for a Randomised Controlled Trial (BECAME Study)
• Estimated Study Start Date: July 2021
• Estimated Primary Completion Date: February 2022
• Estimated Study Completion Date: July 2022

Arms and Interventions

Arm	Intervention/treatment
Experimental: Third dose of BNT162b2 vaccine with Immunosuppression reduction; Third dose of BNT162b2 vaccine with reduction of mycophenolic acid dose	Biological: The Pfizer mRNA-based BNT162b2 vaccine; 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: Third booster dose of BNT162b2 (one standard dose) with no change in immunosuppression protocol; 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).
Experimental: Third dose of BNT162b2 vaccine without immunosuppression reduction; Third dose of BNT162b2 vaccine without reduction of mycophenolic acid dose	Biological: The Pfizer mRNA-based BNT162b2 vaccine; 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: Third booster dose of BNT162b2 (one standard dose) with no change in immunosuppression protocol; 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).
Experimental: Third dose of BNT162b2 vaccine; 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; 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: Third booster dose of BNT162b2 (one standard dose) with no change in immunosuppression protocol; 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).

Outcome Measures

Primary Outcome Measures :

1. positive humoral response against SARS-CoV-2 [ Time Frame: 2 weeks post vaccination ]
   anti-spike protein titer above 50 AU/ml

Secondary Outcome Measures :

1. positive humoral response against SARS-CoV-2 [ Time Frame: 3-, 6-, and 12-months post vaccination ]
   anti-spike protein titer above 50 AU/ml
2. Log transformed titer of anti S protein [ Time Frame: 2 weeks and 3, 6, and 12 months post vaccination ]
3. Adverse events to booster dose [ Time Frame: 2 weeks post vaccine ]
   Severity of adverse events will be assessed using CTCAE v4.0 criteria
4. Acute rejection of the allograft [ Time Frame: 2 weeks, 3,6, and 12 months post vaccination ]
   (either documented by biopsy or clinically suspected, defined as increase in creatinine by 20% from baseline, without any other plausible explanation
5. SARS-CoV-2 infection during the follow up period [ Time Frame: until 12 months following vaccine ]
6. Other viral reactivation during the follow up period [ Time Frame: during the follow up period ]
   VZV, CMV, tested according to clinical suspicion
7. Number of hospitalizations [ Time Frame: until 12 months following vaccine ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• 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

Additional inclusion criteria for the RCT:

• Recipients treated by three anti-rejection medications including: prednisone, tacrolimus, mycophenolate mofetil or mycophenolic acid.
• Tacrolimus trough blood levels 5-10 nGr/ml (lower or higher doses will have to be adjusted before re-considering for inclusion)

Exclusion Criteria:

• Past infection with SARS-CoV-2
• Pregnancy
• Age below 18 years
• Active infection

Additional exclusion criteria for RCT only:

- 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

Contacts and Locations

Contacts

Contact: Ruth Rahaminov; 97239376475; rutir@clalit.org.il

Sponsors and Collaborators

dafna yahav

Investigators

• Principal Investigator: Ruth Rahaminov; Rabin Medical Center, Beilinson Campus, Petah-Tikva, Israel

More Information

• Responsible Party: dafna yahav, Infectious Diseases Unit, Rabin Medical Center, Beilinson Campus, Petah-Tikva, Israel, Rabin Medical Center
• ClinicalTrials.gov Identifier: NCT04961229
• Other Study ID Numbers: 0192-21-RMC
• First Posted: July 14, 2021
• Last Update Posted: July 14, 2021
• Last Verified: July 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: According to request
• Supporting Materials: Study Protocol; Informed Consent Form (ICF)

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by dafna yahav, Rabin Medical Center:

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