drugset / Trial / NCT05081271
COVID-19 Booster Vaccination in Persons With Multiple Sclerosis
Phase 0
Terminated
10 enrolled
Griffin Hospital
Multiple Sclerosis Treatment Center · collabYale-Griffin Prevention Research Center · collab
RandomizedParallel-groupOpen-labelTreatment
Summary
The success of the U.S. vaccination program against SARS-Cov-2 is shown by a dramatic drop in infection rates, hospitalizations and deaths.However, it appears that many persons who take medications that chronically suppress the immune system do not produce neutralizing antibodies to COVID-19 proteins in response to vaccination. This group includes a significant number of persons with multiple sclerosis (PWMS), many of whom are on therapies that chronically suppress their immune function. It is unclear what advice clinicians should provide regarding COVID-19 precautions to patients who fail to develop detectable COVID-19 spike protein antibodies using standard commercially-available tests after a standard series of vaccination, or whether they should test for antibody responses to COVID-19 vaccines in the absence of guidelines. A key research question is whether, in the absence of stopping or reducing potentially immune-altering therapies, there is a way to increase the likelihood of a neutralizing antibody response to COVID-19 vaccination in PWMS who are taking immune suppressive medications.
Timeline
- Start
- 2021-10-15
- Primary completion
- 2022-05-30
- Completion
- 2022-05-30
Publications
- Background Parakkal D, Wooseob K, Paley MA, et al. Glucocorticoids and B Cell Depleting Agents Substantially Impair Immunogenicity of mRNA Vaccines to SARS-CoV-2 medRxiv 2021.04.05.21254656
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- Background Kennedy NA, Lin S, Goodhand JR, Chanchlani N, Hamilton B, Bewshea C, Nice R, Chee D, Cummings JF, Fraser A, Irving PM, Kamperidis N, Kok KB, Lamb CA, Macdonald J, Mehta S, Pollok RC, Raine T, Smith PJ, Verma AM, Jochum S, McDonald TJ, Sebastian S, Lees CW, Powell N, Ahmad T; Contributors to the CLARITY IBD study. Infliximab is associated with attenuated immunogenicity to BNT162b2 and ChAdOx1 nCoV-19 SARS-CoV-2 vaccines in patients with IBD. Gut. 2021 Oct;70(10):1884-1893. doi: 10.1136/gutjnl-2021-324789. Epub 2021 Apr 26.
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- Background Kandimalla R, John A, Abburi C, Vallamkondu J, Reddy PH. Current Status of Multiple Drug Molecules, and Vaccines: An Update in SARS-CoV-2 Therapeutics. Mol Neurobiol. 2020 Oct;57(10):4106-4116. doi: 10.1007/s12035-020-02022-0. Epub 2020 Jul 15.
- Background Polack FP, Thomas SJ, Kitchin N, Absalon J, Gurtman A, Lockhart S, Perez JL, Perez Marc G, Moreira ED, Zerbini C, Bailey R, Swanson KA, Roychoudhury S, Koury K, Li P, Kalina WV, Cooper D, Frenck RW Jr, Hammitt LL, Tureci O, Nell H, Schaefer A, Unal S, Tresnan DB, Mather S, Dormitzer PR, Sahin U, Jansen KU, Gruber WC; C4591001 Clinical Trial Group. Safety and Efficacy of the BNT162b2 mRNA Covid-19 Vaccine. N Engl J Med. 2020 Dec 31;383(27):2603-2615. doi: 10.1056/NEJMoa2034577. Epub 2020 Dec 10.
- 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.
- Background Sadoff J, Gray G, Vandebosch A, Cardenas V, Shukarev G, Grinsztejn B, Goepfert PA, Truyers C, Fennema H, Spiessens B, Offergeld K, Scheper G, Taylor KL, Robb ML, Treanor J, Barouch DH, Stoddard J, Ryser MF, Marovich MA, Neuzil KM, Corey L, Cauwenberghs N, Tanner T, Hardt K, Ruiz-Guinazu J, Le Gars M, Schuitemaker H, Van Hoof J, Struyf F, Douoguih M; ENSEMBLE Study Group. Safety and Efficacy of Single-Dose Ad26.COV2.S Vaccine against Covid-19. N Engl J Med. 2021 Jun 10;384(23):2187-2201. doi: 10.1056/NEJMoa2101544. Epub 2021 Apr 21.
- Background Mohn N, Konen FF, Pul R, Kleinschnitz C, Pruss H, Witte T, Stangel M, Skripuletz T. Experience in Multiple Sclerosis Patients with COVID-19 and Disease-Modifying Therapies: A Review of 873 Published Cases. J Clin Med. 2020 Dec 16;9(12):4067. doi: 10.3390/jcm9124067.
- Background Pinar Morales R, Ramirez Rivas MA, Barrero Hernandez FJ. SARS-CoV-2 infection and seroprevalence in patients with multiple sclerosis. Neurologia (Engl Ed). 2021 Nov-Dec;36(9):698-703. doi: 10.1016/j.nrleng.2021.03.002. Epub 2021 Jun 1.
- Background Giovannoni G. Anti-CD20 immunosuppressive disease-modifying therapies and COVID-19. Mult Scler Relat Disord. 2020 Jun;41:102135. doi: 10.1016/j.msard.2020.102135. Epub 2020 Apr 18. No abstract available.
- Background Sharifian-Dorche M, Sahraian MA, Fadda G, Osherov M, Sharifian-Dorche A, Karaminia M, Saveriano AW, La Piana R, Antel JP, Giacomini PS. COVID-19 and disease-modifying therapies in patients with demyelinating diseases of the central nervous system: A systematic review. Mult Scler Relat Disord. 2021 May;50:102800. doi: 10.1016/j.msard.2021.102800. Epub 2021 Jan 29.
- Background Langer-Gould A, Smith JB, Li BH; KPSC MS Specialist Group. Multiple sclerosis, rituximab, and COVID-19. Ann Clin Transl Neurol. 2021 Apr;8(4):938-943. doi: 10.1002/acn3.51342. Epub 2021 Mar 30.
- Background Kister I, Krogsgaard M, Mulligan MJ, Patskovsky Y, Voloshyna I, Ferstler N, Zhovtis Ryerson L, Curtin R, Kim J, Tardio E, Rimler Z, Sherman K, Samanovic-Golden M, Cornelius A, Lieberman D, Solis S, Pedotti R, Raposo C, Priest J, Hawker K, Silverman GJ. Preliminary Results of Ongoing, Prospective Study of Antibody and TCell Responses to SARS-CoV-2 in Patients With MS on Ocrelizumab or Other Disease-Modifying Therapies. Presented at the 73rd Congress of the American Academy of Neurology (AAN) Virtual 2021; 17-22 April 2021. P15.014
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- Background Achiron A, Mandel M, Dreyer-Alster S, Harari G, Magalashvili D, Sonis P, Dolev M, Menascu S, Flechter S, Falb R, Gurevich M. Author response to: Correspondence to humoral immune response to COVID-19 mRNA vaccine in patients with multiple sclerosis treated with high-efficacy disease-modifying therapies. Ther Adv Neurol Disord. 2021 May 29;14:17562864211020082. doi: 10.1177/17562864211020082. eCollection 2021. No abstract available.
- Background Doria-Rose N, Suthar MS, Makowski M, O'Connell S, McDermott AB, Flach B, Ledgerwood JE, Mascola JR, Graham BS, Lin BC, O'Dell S, Schmidt SD, Widge AT, Edara VV, Anderson EJ, Lai L, Floyd K, Rouphael NG, Zarnitsyna V, Roberts PC, Makhene M, Buchanan W, Luke CJ, Beigel JH, Jackson LA, Neuzil KM, Bennett H, Leav B, Albert J, Kunwar P; mRNA-1273 Study Group. Antibody Persistence through 6 Months after the Second Dose of mRNA-1273 Vaccine for Covid-19. N Engl J Med. 2021 Jun 10;384(23):2259-2261. doi: 10.1056/NEJMc2103916. Epub 2021 Apr 6. No abstract available.
- Background Spencer AJ, McKay PF, Belij-Rammerstorfer S, Ulaszewska M, Bissett CD, Hu K, Samnuan K, Blakney AK, Wright D, Sharpe HR, Gilbride C, Truby A, Allen ER, Gilbert SC, Shattock RJ, Lambe T. Heterologous vaccination regimens with self-amplifying RNA and adenoviral COVID vaccines induce robust immune responses in mice. Nat Commun. 2021 May 17;12(1):2893. doi: 10.1038/s41467-021-23173-1.
- Background The combined use of AstraZeneca and Pfizer vaccines against SARS-CoV-2 offers a powerful immune response (isciii.es). https://www.isciii.es/Noticias/Noticias/Paginas/Noticias/Presentaci%c3%b3n-resultados-preliminares-CombivacS.aspx
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Drugs
| Evaluation | Drug | Modality | Dose | Route |
|---|---|---|---|---|
| Comparator | Ad26.COV2.S | Vaccine | — | — |
| Comparator | BNT162b2 | Messenger RNA (mRNA) | — | — |
| Comparator | Elasomeran | Messenger RNA (mRNA) | — | — |