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

Sponsor

Novartis Pharmaceuticals (Industry)

Overall Status

Active, not recruiting

CT.gov ID

NCT04869358

Collaborator

(none)

Enrollment

Locations

Arms

26.1

Anticipated Duration (Months)

5.7

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
Multiple Sclerosis	Drug: Ofatumumab	Phase 4

Detailed 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.

Study Design

Study Type:

Interventional

Actual Enrollment :

34 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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)

Actual Study Start Date :

May 27, 2021

Actual Primary Completion Date :

May 10, 2022

Anticipated Study Completion Date :

Jul 30, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Vaccination before treatment initiation Patients will receive SARS-CoV-2 mRNA vaccines before starting ofatumumab treatment (approx. 1 month later)	Drug: Ofatumumab Ofatumumab 20 mg s.c. on days 1, 7, 14, week 4 and every 4 weeks thereafter Other Names: OMB157
Experimental: Vaccination during treatment Patients will receive SARS-CoV-2 mRNA vaccines while already stable on ofatumumab treatment (at least 4 weeks since first dose)	Drug: Ofatumumab Ofatumumab 20 mg s.c. on days 1, 7, 14, week 4 and every 4 weeks thereafter Other Names: OMB157

Arm

Intervention/Treatment

Experimental: Vaccination before treatment initiation

Patients will receive SARS-CoV-2 mRNA vaccines before starting ofatumumab treatment (approx. 1 month later)

Drug: Ofatumumab

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

Other Names:

OMB157

Experimental: Vaccination during treatment

Patients will receive SARS-CoV-2 mRNA vaccines while already stable on ofatumumab treatment (at least 4 weeks since first dose)

Drug: Ofatumumab

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

Other Names:

OMB157

Outcome Measures

Primary Outcome Measures

Percentage of RMS patients having established SARS-CoV-2-specific T cells after receiving a modRNA vaccine [at 1 month after second dose of vaccine or booster 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

Secondary Outcome Measures

Percentage of participants achieving seroconversion [at baseline, 1 week, 1 , 6, 12 and 18 months after second dose of vaccine or 1,6 and 12 months after booster vaccine]
SARS-CoV-2 neutralizing antibodies measured at the central laboratory
Percentage of participants maintaining SARS-CoV-2 specific T-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]
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
Immunophenotyping of 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]
Phenotypic description of the cellular immune response performed at the central laboratory by FACS analysis
Number of treatment emergent adverse events, serious adverse events and COVID-19 infections [Up to 18 months after second dose of vaccine or 12 months after booster vaccine]
Untoward medical occurrences (including abnormal laboratory tests, vital signs and other safety assessments) will be captured as adverse events including COVID-19 infections

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 100 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	Country	Postal Code
1	Novartis Investigative Site	Berlin	Germany	13353
2	Novartis Investigative Site	Bielefeld	Germany	D 33647
3	Novartis Investigative Site	Dresden	Germany	01307
4	Novartis Investigative Site	Erbach	Germany	64711
5	Novartis Investigative Site	Siegen	Germany	57076
6	Novartis Investigative Site	Unterhaching	Germany	82008