Third Dose of Moderna COVID-19 Vaccine in Transplant Recipients

A Randomised, Blinded, Controlled Trial of a Third Dose of Moderna COVID-19 Vaccine Versus Placebo in Solid Organ Transplant Recipients

This study will be a randomized, double-blind, placebo-controlled trial of a third dose of Moderna vaccine versus placebo. Participants will be those that have received two doses of mRNA-1273 COVID vaccine (Moderna) at 0 and 1 months. Participants will be randomized 1:1 to receive either a third dose of the mRNA-1273 vaccine or saline placebo at 3 months post initial vaccination.

Study Overview

• Status: Completed
• Conditions: Covid19; Vaccine Response Impaired; Immune Suppression
• Intervention / Treatment: Biological: mRNA-1273 vaccine; Other: Normal Saline Placebo

Detailed Description

Solid organ transplant (SOT) recipients are at high risk of COVID-19 complications. The Moderna vaccine (mRNA-1273) has proven highly efficacious and safe in a phase III large, randomized controlled trial of 30,420 persons in the general population, and has been in use in Canada since December 2020. SOT patients show diminished response to mRNA vaccines in several studies with approximately 40-50% positive antibody after the second dose. In positive patients, antibody titers are lower than the general population and adverse events mirror the general population. The current study will recruit 120 SOT recipients who have received both scheduled doses of the Moderna vaccine at 0 and 1 months. The hypothesis is that a third dose of vaccine will significantly increase antibody titers. SOT participants will be recruited and randomized 1:1 to receive an additional dose of Moderna COVID-19 vaccine two months after the last dose vs saline placebo. The outcomes will measure anti-RBD antibody titer, T-cell immunity, local/systemic side effects, and rejection events.

• Study Type: Interventional
• Enrollment (Actual): 120
• Phase: Phase 4

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5G2N2
      • University Health Network, Toronto General Hospital, Multi-Organ Transplant
    • Toronto, Ontario, Canada, M5G 2N2
      • University Health Network, Toronto General Hospital

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Solid organ transplant recipient who has previously received Moderna vaccine at 0 and 1 months
• Able to provide informed consent

Exclusion Criteria:

• Anaphylaxis or allergic reaction to Moderna vaccine

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Experimental group; Participants will receive a one dose of mRNA-1273 vaccine 0.5mL i.m. in deltoid muscle	Biological: mRNA-1273 vaccine; COVID vaccine 3rd dose; Other Names: Moderna COVID-19 vaccine
Placebo Comparator: Comparator Group; Participants will receive one dose of normal saline injection 0.5mL i.m. in deltoid muscle	Other: Normal Saline Placebo; Normal Saline Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
anti-RBD antibody titer	Percentage of patients that achieve anti-RBD of >=100 U/mL in each arm	4-6 weeks after intervention

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse events	Percentage of patient with local and systemic adverse events	7 days after intervention
T-cell response	Proportion of participants with an increase in polyfunctional T-cell response compared to pre-vaccination	4-6 weeks after intervention

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
SARS-CoV-2 infection	Number of patients with microbiologically proven infection	6 months after intervention
Rejection	Proportion of patients with biopsy-proven or clinically treated graft rejection	4 weeks after intervention

Collaborators and Investigators

• Sponsor: University Health Network, Toronto

Publications and helpful links

General Publications

• Baden LR, El Sahly HM, Essink B, Kotloff K, Frey S, Novak R, Diemert D, Spector SA, Rouphael N, Creech CB, McGettigan J, Khetan S, Segall N, Solis J, Brosz A, Fierro C, Schwartz H, Neuzil K, Corey L, Gilbert P, Janes H, Follmann D, Marovich M, Mascola J, Polakowski L, Ledgerwood J, Graham BS, Bennett H, Pajon R, Knightly C, Leav B, Deng W, Zhou H, Han S, Ivarsson M, Miller J, Zaks T; COVE Study Group. Efficacy and Safety of the mRNA-1273 SARS-CoV-2 Vaccine. N Engl J Med. 2021 Feb 4;384(5):403-416. doi: 10.1056/NEJMoa2035389. Epub 2020 Dec 30.
• Kumar D, Ferreira VH, Hall VG, Hu Q, Samson R, Ku T, Ierullo M, Majchrzak-Kita B, Tomlinson G, Gingras AC, Humar A. Neutralization of SARS-CoV-2 Variants in Transplant Recipients After Two and Three Doses of mRNA-1273 Vaccine : Secondary Analysis of a Randomized Trial. Ann Intern Med. 2022 Feb;175(2):226-233. doi: 10.7326/M21-3480. Epub 2021 Nov 23.

Study record dates

Study Major Dates

• Study Start (Actual): May 25, 2021
• Primary Completion (Actual): July 30, 2021
• Study Completion (Actual): August 30, 2021

Study Registration Dates

• First Submitted: May 9, 2021
• First Submitted That Met QC Criteria: May 9, 2021
• First Posted (Actual): May 13, 2021

Study Record Updates

• Last Update Posted (Actual): August 2, 2022
• Last Update Submitted That Met QC Criteria: July 29, 2022
• Last Verified: July 1, 2022

More Information

Terms related to this study

• Keywords: vaccine; solid organ transplant
• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19; Physiological Effects of Drugs; Immunologic Factors; Vaccines
• Other Study ID Numbers: 21-5324.0

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes