COVID-19 Vaccine Response in Treated MS Patients

NCT05060354 | Completed

• 1 other identifier: COMB157GUS19T
• Study Type: observational
• Target: 159
• Locations: 1 country
• Sites: 1

Brief Summary

The primary goal of this study is to assess the impact of the two major disease modifying therapy (DMT) classes (B cell therapies and S1P modulators) on humoral and cell-mediated immunity to SARS- CoV-2 vaccination compared to non-MS controls. We have chosen to compare DMT-treated MS patients to non-MS controls because the pivotal vaccine studies were conducted in non-MS healthy control groups in which there is significant clinical data and validated assays for antibody responses.

Conditions

Multiple Sclerosis; Healthy

Keywords

Multiple Sclerosis; COVID-19; mRNA vaccine

Outcome Measures

Primary Outcomes (1)

• Primary endpoint

  Compare the percentage of MS patients on immunotherapy with a positive SARS-CoV-2 Spike antibody response, using the Roche Elecsys® Anti-SARS-CoV-2 S immunoassay for the quantitative, in vitro determination of antibodies to SARS-CoV- 2 in human serum and plasma. It is an Electro-chemiluminescence immunoassay (ECLIA) test using a double-antigen sandwich assay. A positive seroconversion defined as level\>0.4U/ml.

  11-12 months

Secondary Outcomes (5)

• Secondary endpoint 1

  11-12 months

• Secondary endpoint 2

  5-6 months

• Secondary endpoint 3

  11-12 months

• Secondary endpoint 4

  11-12 months

• Secondary endpoint 5

  11-12 months

Study Arms (4)

MS Kesimpta (ofatumumab)

MS patients treated with Kesimpta (ofatumumab) for at least 3 months prior to SARS-CoV2 vaccination (completed regimen) Drug administration n/a, following routine clinical care Blood draws at 2-3 months, 5-6 months, and 11-12 months after enrollment

Other: Blood draw

MS Ocrevus (ocrelizumab)

MS patients treated with Ocrevus (ocrelizumab) for at least 3 months prior to SARS-CoV2 vaccination (completed regimen) Drug administration n/a, following routine clinical care Blood draws at 2-3 months, 5-6 months, and 11-12 months after enrollment

Other: Blood draw

MS Gilenya (fingolimod) and Mayzent (siponimod)

MS patients treated with Gilenya (fingolimod) or Mayzent (siponimod) for at least 3 months prior to SARS-CoV2 vaccination (completed regimen) Drug administration n/a, following routine clinical care Blood draws at 2-3 months, 5-6 months, and 11-12 months after enrollment

Other: Blood draw

Healthy Control

Individuals with major autoimmune disorders or current treatment with immunosuppressive or immunomodulatory drugs Received SARS-CoV2 vaccination (completed regimen) within 2-6 months of enrollment Blood draws at 2-3 months, 5-6 months, and 11-12 months after enrollment

Other: Blood draw

Interventions

Blood draw OTHER

Approximately 120 mL whole blood will be collected from each subject at each timepoint

Healthy Control; MS Gilenya (fingolimod) and Mayzent (siponimod); MS Kesimpta (ofatumumab); MS Ocrevus (ocrelizumab)

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

For this study, we will prospectively collect data and biospecimens from MS patients and healthy volunteers. MS patients will largely be recruited from the Brigham MS Center at Brigham and Women's Hospital (Boston MA US). Healthy volunteers will be recruited from the community surrounding BWH and through IRB-approved recruitment advertisements. The Brigham MS Center sees 2500 patients annually and is adjacent to an ongoing COVID vaccine clinic.

You may qualify if:

• For MS Patients:
• Diagnosis of MS
• Treatment with one of the four DMTs (Kesimpta (ofatumumab), Ocrevus (ocrelizumab), Gilenya (fingolimod), Mayzent (siponimod)) for at least 3 months prior to first SARS-CoV2 vaccine dose
• SARS-CoV2 vaccine regimen complete within the past 2-3 or 5-6 months (either Moderna® or Pfizer-BioNTech® mRNA vaccines)
• Age 18-65, inclusive
• For Health Controls:
• \. Age 18-65, inclusive

You may not qualify if:

• For MS Patients:
• \. Prior known COVID-19 infection
• For Health Controls:
• Prior known COVID-19 infection
• major autoimmune disorders or current treatment with immunosuppressive or immunomodulatory drugs

Sponsors & Collaborators

• Brigham and Women's Hospital: lead

Study Sites (1)

Brigham MS Center

Boston, Massachusetts, 02115, United States

Location

Related Publications (7)

• Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, Zhang L, Fan G, Xu J, Gu X, Cheng Z, Yu T, Xia J, Wei Y, Wu W, Xie X, Yin W, Li H, Liu M, Xiao Y, Gao H, Guo L, Xie J, Wang G, Jiang R, Gao Z, Jin Q, Wang J, Cao B. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020 Feb 15;395(10223):497-506. doi: 10.1016/S0140-6736(20)30183-5. Epub 2020 Jan 24.

  PMID: 31986264 BACKGROUND

• Zhou P, Yang XL, Wang XG, Hu B, Zhang L, Zhang W, Si HR, Zhu Y, Li B, Huang CL, Chen HD, Chen J, Luo Y, Guo H, Jiang RD, Liu MQ, Chen Y, Shen XR, Wang X, Zheng XS, Zhao K, Chen QJ, Deng F, Liu LL, Yan B, Zhan FX, Wang YY, Xiao GF, Shi ZL. A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature. 2020 Mar;579(7798):270-273. doi: 10.1038/s41586-020-2012-7. Epub 2020 Feb 3.

  PMID: 32015507 BACKGROUND

• Xu Z, Shi L, Wang Y, Zhang J, Huang L, Zhang C, Liu S, Zhao P, Liu H, Zhu L, Tai Y, Bai C, Gao T, Song J, Xia P, Dong J, Zhao J, Wang FS. Pathological findings of COVID-19 associated with acute respiratory distress syndrome. Lancet Respir Med. 2020 Apr;8(4):420-422. doi: 10.1016/S2213-2600(20)30076-X. Epub 2020 Feb 18. No abstract available.

  PMID: 32085846 BACKGROUND

• Wu Z, McGoogan JM. Characteristics of and Important Lessons From the Coronavirus Disease 2019 (COVID-19) Outbreak in China: Summary of a Report of 72 314 Cases From the Chinese Center for Disease Control and Prevention. JAMA. 2020 Apr 7;323(13):1239-1242. doi: 10.1001/jama.2020.2648. No abstract available.

  PMID: 32091533 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.

  PMID: 33378609 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.

  PMID: 33301246 BACKGROUND

• Conway S, Saxena S, Baecher-Allan C, Krishnan R, Houtchens M, Glanz B, Saraceno TJ, Polgar-Turcsanyi M, Bose G, Bakshi R, Bhattacharyya S, Galetta K, Kaplan T, Severson C, Singhal T, Stazzone L, Zurawski J, Paul A, Weiner HL, Healy BC, Chitnis T. Preserved T cell but attenuated antibody response in MS patients on fingolimod and ocrelizumab following 2nd and 3rd SARS-CoV-2 mRNA vaccine. Mult Scler J Exp Transl Clin. 2023 Apr 5;9(2):20552173231165196. doi: 10.1177/20552173231165196. eCollection 2023 Apr-Jun.

  PMID: 37057191 DERIVED

Related Links

• Network recruitment site

Biospecimen

Retention: SAMPLES WITHOUT DNA

Approximately 120 mL whole blood will be collected from each subject at each timepoint: 20 mL will be sent to the BWH clinical laboratories for same day SARS-CoV2 antibody assays and immunoglobulin levels. Additional blood for research immune assays will be collected and stored: 60-70 mL will be collected in cell preparation tubes (CPTs) for peripheral blood mononuclear cell (PBMC) isolation, 10 mL for DNA isolation and 20 mL by serum separator tubes for serum collection using a standardized sample collection kit. PBMCs will isolated and stored in liquid nitrogen and serum will be frozen at -80 °C.

MeSH Terms

Conditions

Multiple Sclerosis; COVID-19

Interventions

Blood Specimen Collection

Condition Hierarchy (Ancestors)

Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases; Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Investigative Techniques

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Senior Neurologist, Professor of Neurology

Study Record Dates

• First Submitted: September 27, 2021
• First Posted: September 29, 2021
• Study Start: June 1, 2021
• Primary Completion: September 15, 2023
• Study Completion: September 28, 2023
• Last Updated: January 25, 2024

Record last verified: 2024-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)