Exploring the Immune Response to SARS-CoV-2 COVID-19 Vaccines in Patients With Relapsing Multiple Sclerosis (RMS) Treated With Ofatumumab

Multiple Sclerosis Clinical Trial

— KYRIOS  

Official title:

Tracking the Immune Response to SARS-CoV-2 modRNA Vaccines in an Open-label Multicenter Study in Participants With Relapsing Multiple Sclerosis Treated With Ofatumumab s.c. (KYRIOS)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04869358
• Other study ID #: COMB157GDE01
• Status: Completed
• Phase: Phase 4
• Start date: May 27, 2021
• Est. completion date: June 13, 2023

Study information

• Verified date: September 2023
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study aims to understand whether patients with MS can mount an immune response to SARS-CoV-2 mRNA vaccines (initial vaccinations or booster vaccines) when vaccinated either before initiation of ofatumumab treatment or at least 4 weeks after commencing ofatumumab treatment.

Description:

This is a two cohort, multicenter, open-label, prospective study of 40 (optionally up to 60) patients with relapsing multiple sclerosis (RMS) planning to undergo a SARS-CoV-2 mRNA vaccination (initial vaccinations or booster vaccines) as part of clinical routine. The maximal duration of the study for an individual patient is 22 months.

• The first cohort will be RMS patients receiving SARS-CoV-2 mRNA vaccine (initial vaccinations or booster vaccines) as part of clinical routine prior to starting ofatumumab treatment.

• The second cohort will be participants receiving SARS-CoV-2 mRNA vaccine (initial vaccinations or booster vaccines) as part of clinical routine while already stable on ofatumumab treatment for at least 4 weeks (since first dose).

Development of SARS-CoV-2 specific T-cells and functional anti-SARS-CoV-2 antibodies will be investigated for up to 18 months after the participants' vaccination.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 34
• Est. completion date: June 13, 2023
• Est. primary completion date: May 10, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 100 Years

Eligibility

Inclusion Criteria:

• Relapsing Multiple Sclerosis (RMS) diagnosis

• eligible for ofatumumab treatment

• willing and eligible to receive SARS-CoV-2 mRNA vaccine

Exclusion Criteria:

• known prior or current COVID-19 infection

• previous treatment with BTK inhibitor or anti-CD20 therapy other than ofatumumab

Other protocol-defined inclusion/exclusion criteria may apply

Related Conditions & MeSH terms

• Multiple Sclerosis
• Sclerosis

Intervention

Drug:
• Ofatumumab
Ofatumumab 20 mg s.c. on days 1, 7, 14, week 4 and every 4 weeks thereafter

Locations

Country	Name	City	State
Germany	Novartis Investigative Site	Berlin
Germany	Novartis Investigative Site	Bielefeld
Germany	Novartis Investigative Site	Dresden
Germany	Novartis Investigative Site	Erbach
Germany	Novartis Investigative Site	Siegen
Germany	Novartis Investigative Site	Unterhaching

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of RMS patients having established SARS-CoV-2-specific T cells after receiving a modRNA vaccine	Detection of SARS-CoV-2 specific T-cells measured at the central laboratory e.g. by enzyme-linked immunosorbent spot (ELIspot) assay from peripheral blood mononuclear cells	at 1 month after second dose of vaccine or booster vaccine
Secondary	Percentage of participants achieving seroconversion	SARS-CoV-2 neutralizing antibodies measured at the central laboratory	at baseline, 1 week, 1 , 6, 12 and 18 months after second dose of vaccine or 1,6 and 12 months after booster vaccine
Secondary	Percentage of participants maintaining SARS-CoV-2 specific T-cells	Maintenance of SARS-CoV-2 specific T-cells over time measured at the central laboratory e.g. by enzyme-linked immunosorbent spot (ELIspot) assay from peripheral blood mononuclear cells	at baseline, 1 week, 1 , 6, 12 and 18 months after second dose of vaccine or 1,6 and 12 months after booster vaccine
Secondary	Immunophenotyping of peripheral blood mononuclear cells	Phenotypic description of the cellular immune response performed at the central laboratory by FACS analysis	at baseline, 1 week, 1 , 6, 12 and 18 months after second dose of vaccine or 1,6 and 12 months after booster vaccine
Secondary	Number of treatment emergent adverse events, serious adverse events and COVID-19 infections	Untoward medical occurrences (including abnormal laboratory tests, vital signs and other safety assessments) will be captured as adverse events including COVID-19 infections	Up to 18 months after second dose of vaccine or 12 months after booster vaccine