Clinical trial NCT04885907: Third Dose of Moderna COVID-19 Vaccine in Transplant Recipients
Official title: A Randomised, Blinded, Controlled Trial of a Third Dose of Moderna COVID-19 Vaccine Versus Placebo in Solid Organ Transplant Recipients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Vaccine Response Impaired
Immune Suppression
Covid19
Keywords: solid organ transplant
vaccine
Lead sponsor: University Health Network, Toronto
Sponsor class: OTHER
First posted: 2021-05-13
Enrollment: 120
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomised, placebo-controlled trial
Primary purpose: PREVENTION

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: anti-RBD antibody titer
timeFrame: 4-6 weeks after intervention
Secondary outcomes:
measure: Adverse events
timeFrame: 7 days after intervention
measure: T-cell response
timeFrame: 4-6 weeks after intervention
Other outcomes:
measure: SARS-CoV-2 infection
timeFrame: 6 months after intervention
measure: Rejection
timeFrame: 4 weeks after intervention
Locations:
city: Toronto
country: Canada
facility: University Health Network, Toronto General Hospital
state: Ontario
city: Toronto
country: Canada
facility: University Health Network, Toronto General Hospital, Multi-Organ Transplant
state: Ontario
Study officials:
affiliation: University Health Network, Toronto
name: Deepali Kumar, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.