A Open-label Study to Assess Response to COVID-19 Vaccine in Multiple Sclerosis Participants Treated With Ofatumumab

Phase 4

Terminated

• Conditions: Relapsing Multiple Sclerosis (RMS)
• Interventions: Drug: Ofatumumab; Biological: mRNA COVID-19 vaccine; Drug: interferon or glatiramer acetate

• Registration Number: NCT04878211
• Lead Sponsor: Novartis Pharmaceuticals

Brief Summary

This study evaluated if relapsing multiple sclerosis (MS) participants treated with ofatumumab 20 mg subcutaneous (s.c.) administered once monthly could develop an adequate immune response to the COVID-19 mRNA vaccine compared to participants on an interferon or glatiramer acetate.

Detailed Description

This was a six-cohort, multicenter, prospective study planned for up to 88 relapsing multiple sclerosis (MS) participants. The study was intended to address two questions: 1) Can participants treated with ofatumumab develop an immune response if receiving a COVID-19 mRNA vaccine two weeks prior to ofatumumab start? 2) If receiving COVID-19 mRNA vaccine after introduction of ofatumumab treatment, can participants develop an immune response? Cohort 1: participants received an mRNA COVID-19 vaccine at least two weeks prior to ofatumumab start. Cohort 2: participants received an mRNA COVID-19 vaccine at least four weeks after beginning ofatumumab. Cohort 3: participants on an interferon or glatiramer acetate who received COVID-19 mRNA vaccine. Cohort 4: participants fully vaccinated with an RNA COVID-19 vaccine at least four weeks after ofatumumab start. Cohort 5: participants vaccinated with an RNA COVID-19 vaccine, with or without a booster dose, and on interferon or glatiramer acetate. Cohort 6: participants fully vaccinated with an RNA COVID-19 vaccine who received a booster dose at least four weeks after ofatumumab start. Participants obtained the COVID-19 mRNA vaccine from their HCP (private insurance) or appropriate federal, state or local program.

Participants in Cohort 1 received loading doses of ofatumumab and subsequent dosing was 20 mg s.c. administered monthly. All other cohorts continued current dosing schedule of either ofatumumab, glatiramer acetate or interferon. Participation in trial was maximum of 421 days which was dependent on the Cohort.

Study Timeline

• Study First Submitted: 2021-05-03
• Study First Submitted QC: 2021-05-06
• Study First Posted: 2021-05-07
• Study Start: 2021-06-10
• Primary Completion: 2023-04-14
• Study Completion: 2023-04-14
• Results First Submitted: 2024-03-25
• Status Verified: 2024-06
• Results First Submitted QC: 2024-06-17
• Last Update Submitted: 2024-06-17
• Results First Posted: 2024-06-20
• Last Update Posted: 2024-06-20

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 24

Inclusion Criteria

• Signed informed consent must be obtained prior to participation in the study
• Diagnosis of relapsing MS by 2017 revised McDonald criteria
• Were willing to comply with the study schedule
• Cohort 1: Were receiving an mRNA COVID-19 vaccine (Pfizer or Moderna vaccine) at least two weeks prior to starting ofatumumab
• Cohort 2: Were receiving an mRNA COVID-19 vaccine (Pfizer or Moderna vaccine) and on ofatumumab for at least 4 weeks
• Cohort 3: Were receiving an mRNA COVID-19 vaccine (Pfizer or Moderna vaccine) and on interferon or glatiramer acetate for at least 4 weeks
• Cohort 4: Fully vaccinated with a non-live COVID mRNA vaccine (Pfizer or Moderna vaccine) and on ofatumumab for at least 4 weeks
• Cohort 5: Fully vaccinated with a non-live COVID mRNA vaccine (Pfizer or Moderna vaccine), with or without a booster, and on interferon or glatiramer acetate for at least 4 weeks
• Cohort 6: Fully vaccinated with a non-live COVID mRNA vaccine, (Pfizer or Moderna vaccine), with a booster, and on ofatumumab for at least 4 weeks

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Exclusion Criteria

• Received the J&J vaccine.
• Had a contraindication to receiving an mRNA COVID-19 vaccine
• Had an immediate allergic reaction to past vaccine or injection
• Experienced a major episode of infection requiring hospitalization or treatment with intravenous antibiotics within 2 weeks prior to the screening visit

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Cohort 4 - Fully vaccinated and on OMB457 ≥ 4 WKs	mRNA COVID-19 vaccine	Participants fully vaccinated with a non-live COVID mRNA vaccine and on ofatumumab for at least 4 weeks (20 mg subcutaneous)
Cohort 1 - 2 WKs vaccine prior to OMB157	mRNA COVID-19 vaccine	Participants received non-live COVID-19 mRNA vaccine at least two weeks prior to start of ofatumumab (OMB157) (20 mg subcutaneous).
Cohort 2 - vaccine 4 WKs after OMB157	Ofatumumab	Participants received non-live COVID-19 mRNA vaccine at least four weeks after start of ofatumumab (OMB157) (20 mg subcutaneous).
Cohort 2 - vaccine 4 WKs after OMB157	mRNA COVID-19 vaccine	Participants received non-live COVID-19 mRNA vaccine at least four weeks after start of ofatumumab (OMB157) (20 mg subcutaneous).
Cohort 3 - Interferon or glatiramer acetate - vaccine 4 WKs after	mRNA COVID-19 vaccine	Participants will receive non-live COVID-19 mRNA vaccine at least 4 weeks after start of prescribed interferon or glatiramer acetate
Cohort 3 - Interferon or glatiramer acetate - vaccine 4 WKs after	interferon or glatiramer acetate	Participants will receive non-live COVID-19 mRNA vaccine at least 4 weeks after start of prescribed interferon or glatiramer acetate
Cohort 5 -Fully vaccinated, on interferon or glatiramer acetate for ≥ 4 WKs ± booster	mRNA COVID-19 vaccine	Participants fully vaccinated with a non-live COVID mRNA vaccine, without or without a booster, and on interferon or glatiramer acetate for at least 4 weeks.
Cohort 5 -Fully vaccinated, on interferon or glatiramer acetate for ≥ 4 WKs ± booster	interferon or glatiramer acetate	Participants fully vaccinated with a non-live COVID mRNA vaccine, without or without a booster, and on interferon or glatiramer acetate for at least 4 weeks.
Cohort 6 - Fully vaccinated, currently on OMB457 for ≥ 4 WKs, + booster	mRNA COVID-19 vaccine	Participants fully vaccinated with a non-live COVID mRNA vaccine with a booster and on ofatumumab for at least 4 weeks (20 mg subcutaneous)
Cohort 1 - 2 WKs vaccine prior to OMB157	Ofatumumab	Participants received non-live COVID-19 mRNA vaccine at least two weeks prior to start of ofatumumab (OMB157) (20 mg subcutaneous).
Cohort 4 - Fully vaccinated and on OMB457 ≥ 4 WKs	Ofatumumab	Participants fully vaccinated with a non-live COVID mRNA vaccine and on ofatumumab for at least 4 weeks (20 mg subcutaneous)
Cohort 6 - Fully vaccinated, currently on OMB457 for ≥ 4 WKs, + booster	Ofatumumab	Participants fully vaccinated with a non-live COVID mRNA vaccine with a booster and on ofatumumab for at least 4 weeks (20 mg subcutaneous)

Primary Outcome Measures

Name	Time	Method
Percentage of Participants With Response by SARS-CoV-2 Qualitative IgG Antibody Assay at 14 Days Post-vaccination by Cohort Group and Overall, Non-response Imputation Approach (Safety Analysis Set)	Cohorts 1 - 3: >=14 days after vaccination: Day 36 (Pfizer) or Day 43 (Moderna); Cohorts 4-6: Day 1	An immune response is defined as a positive SARS-CoV-2 qualitative IgG antibody assay ≥14 days after full course \[2 doses\] vaccination to non live mRNA COVID-19 vaccine, Participants with a negative or borderline result were considered non-responders, as well as participants with a missing or invalid immune response assessment at 14 days post-vaccination (imputed as non-responders).

Secondary Outcome Measures

Name	Time	Method
Percentage of Patients With an Immune Response by SARS-CoV-2 Qualitative IgG Antibody Assay by Time Point, Cohort Group and Overall, Non-response Imputation Approach (Safety Analysis Set)	Vaccination up to 70, 180, 270 and 360 days	An immune response is defined as a positive SARS-CoV-2 qualitative IgG antibody assay ≥14 days after full course \[2 doses\] vaccination to non live mRNA COVID-19 vaccine, Participants with a negative or borderline result were considered non-responders, as well as participants with a missing or invalid immune response assessment at 14 days post-vaccination (imputed as non-responders).
Percentage of Participants Achieving Immune Conversion by Individual Cohort Group and Overall, Non-response Imputation Approach (Safety Analysis Set)	Cohorts 1 - 3: >=14 days after vaccination: Day 36 (Pfizer) or Day 43 (Moderna); Cohorts 4-5: Day 1	Immune conversion was defined as (i) pre-vaccination absence of SARS-CoV-2 qualitative IgG antibody with any post-vaccination positive SARS-CoV-2 qualitative IgG antibody assay (Cohorts 1-3 only); or (ii) pre vaccination presence of SARS-CoV-2 quantitative IgG antibody (i.e., pre vaccination value ≥0.80 U/mL) with any post-vaccination ≥4-fold increase in SARS-CoV-2 quantitative IgG antibody titer (Cohorts 1-3 only); or (iii) initial negative SARS-CoV-2 nucleocapsid antibody assay with any post-vaccination positive SARS-CoV-2 qualitative IgG antibody assay (Cohorts 4 and 5 only). There was no baseline for Cohort 6 because there was no blood collection prior to vaccination.

Trial Locations

Locations (7)

Dragonfly Research LLC; 🇺🇸 Wellesley, Massachusetts, United States

Minnesota Center Multiple Sclerosis; 🇺🇸 Plymouth, Minnesota, United States

The MS Center for Innovation in Care; 🇺🇸 Saint Louis, Missouri, United States

Dayton Center for Neurological Disorders; 🇺🇸 Centerville, Ohio, United States

The Neurological Institute PA; 🇺🇸 Charlotte, North Carolina, United States

Center For Neurology and Spine; 🇺🇸 Phoenix, Arizona, United States

Infinity Clinical Research LLC .; 🇺🇸 Hollywood, Florida, United States