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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Experimental group | Active Comparator | Participants will receive a one dose of mRNA-1273 vaccine 0.5mL i.m. in deltoid muscle |
|
| Comparator Group | Placebo Comparator | Participants will receive one dose of normal saline injection 0.5mL i.m. in deltoid muscle |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| mRNA-1273 vaccine | Biological | COVID vaccine 3rd dose |
|
| 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 |
| 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 |
| 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 |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Deepali Kumar, MD | University Health Network, Toronto | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University Health Network, Toronto General Hospital | Toronto | Ontario | M5G 2N2 | Canada | ||
| University Health Network, Toronto General Hospital, Multi-Organ Transplant |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 33378609 | Background | 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. | |
| 34807716 |
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| ID | Term |
|---|---|
| D000086382 | COVID-19 |
| ID | Term |
|---|---|
| D011024 | Pneumonia, Viral |
| D011014 | Pneumonia |
| D012141 | Respiratory Tract Infections |
| D007239 | Infections |
Not provided
Not provided
| ID | Term |
|---|---|
| D000090983 | 2019-nCoV Vaccine mRNA-1273 |
| ID | Term |
|---|---|
| D000087503 | mRNA Vaccines |
| D000087504 | Nucleic Acid-Based Vaccines |
| D014614 | Vaccines, Synthetic |
| D011994 | Recombinant Proteins |
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Randomised, placebo-controlled trial
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Participant and vaccinator will be blinded to vaccine vs placebo
| Normal Saline Placebo | Other | Normal Saline Placebo |
|
| 4-6 weeks after intervention |
| 4 weeks after intervention |
| Toronto |
| Ontario |
| M5G2N2 |
| Canada |
| Derived |
| 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. |
| D014777 |
| Virus Diseases |
| D018352 | Coronavirus Infections |
| D003333 | Coronaviridae Infections |
| D030341 | Nidovirales Infections |
| D012327 | RNA Virus Infections |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
| D014612 | Vaccines |
| D001688 | Biological Products |
| D045424 | Complex Mixtures |
| D000086663 | COVID-19 Vaccines |
| D014765 | Viral Vaccines |
| D000941 | Antigens |
| D001685 | Biological Factors |