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

Relapsing Multiple Sclerosis (RMS) Clinical Trial

Official title:

An Open-label Multicenter Study to Assess Response to COVID-19 Vaccine in Participants With Multiple Sclerosis Treated With Ofatumumab 20 mg Subcutaneously

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT04878211
• Other study ID #: COMB157GUS16
• Status: Terminated
• Phase: Phase 4
• Start date: June 10, 2021
• Est. completion date: April 14, 2023

Study information

• Verified date: June 2024
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 24
• Est. completion date: April 14, 2023
• Est. primary completion date: April 14, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 55 Years

Eligibility

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

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

Related Conditions & MeSH terms

• COVID-19
• Multiple Sclerosis
• Relapsing Multiple Sclerosis (RMS)
• Sclerosis

Intervention

Drug:
• Ofatumumab
3 loading doses followed by monthly administrations

Biological:
• mRNA COVID-19 vaccine
Pfizer or Moderna mRNA Vaccine

Drug:
• interferon or glatiramer acetate
iDMT

Locations

Country	Name	City	State
United States	Dayton Center for Neurological Disorders	Centerville	Ohio
United States	The Neurological Institute PA	Charlotte	North Carolina
United States	Infinity Clinical Research LLC .	Hollywood	Florida
United States	Center For Neurology and Spine	Phoenix	Arizona
United States	Minnesota Center Multiple Sclerosis	Plymouth	Minnesota
United States	The MS Center for Innovation in Care	Saint Louis	Missouri
United States	Dragonfly Research LLC	Wellesley	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)	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).	Cohorts 1 - 3: >=14 days after vaccination: Day 36 (Pfizer) or Day 43 (Moderna); Cohorts 4-6: Day 1
Secondary	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)	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).	Vaccination up to 70, 180, 270 and 360 days
Secondary	Percentage of Participants Achieving Immune Conversion by Individual Cohort Group and Overall, Non-response Imputation Approach (Safety Analysis Set)	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.	Cohorts 1 - 3: >=14 days after vaccination: Day 36 (Pfizer) or Day 43 (Moderna); Cohorts 4-5: Day 1