Relapsing Multiple SclerosisPhase 4KYRIOSNCT04869358

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

A Phase 4 study testing Ofatumumab in people with Relapsing Multiple Sclerosis, run by Novartis Pharmaceuticals at 6 sites in Germany.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

This study aimed to understand whether patients with relapsing multiple sclerosis (RMS) 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. Read more about this study

Who is it for?: Ages 18 to 100 years
Conditions the study is for: Relapsing Multiple Sclerosis
What is being tested?: Ofatumumab
Type of treatment: Vaccines
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 34 participants
Where: 6 sitesGermany
Study dates: 27 May 2021to 13 Jun 2023
Phase: Phase 4
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 100 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Relapsing Multiple Sclerosis (RMS) diagnosis
eligible for ofatumumab treatment
willing and eligible to receive SARS-CoV-2 mRNA vaccine

Who cannot join

known prior or current COVID-19 infection
previous treatment with BTK inhibitor or anti-CD20 therapy other than ofatumumab
no previous vaccination with a non-modRNA SARS-CoV-2 vaccine.
Other protocol-defined inclusion/exclusion criteria may apply

Trial locations and contacts

6 sites in 1 country.

City, postcode or hospital

6 sites in 1 country

Germany6 sites

Novartis Investigative Site
Berlin, 13353
Novartis Investigative Site
Bielefeld, D 33647
Novartis Investigative Site
Dresden, 01307
Novartis Investigative Site
Erbach im Odenwald, 64711
Novartis Investigative Site
Siegen, 57076
Novartis Investigative Site
Unterhaching, 82008

Other trials in Germany

About this study

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)

Read the detailed description

This was a four cohort, multicenter, open-label, prospective study of 34 (optionally up to 60) patients who had 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 was 22 months.

The first cohort was 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 was 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).

Cohort 1a - Patients received first SARS-CoV-2 vaccination within the study prior to starting ofatumumab treatment.

Cohort 1b - Patients had already completed initial vaccination cycle and received a booster vaccine within the study prior to starting ofatumumab treatment.

Cohort 2a - Patients who received their first SARS-CoV-2 vaccination within the study while already stable on ofatumumab treatment for at least 4 weeks (since the first dose).

Cohort 2b - Patients who had already completed their initial vaccination cycle and received a booster vaccine within the study while already stable on ofatumumab treatment for at least 4 weeks (since the first dose).

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

Conditions: Relapsing Multiple Sclerosis
Being tested: Ofatumumab
Keywords: COVID-19, SARS-CoV-2 mRNA vaccine, immune response, Ofatumumab, Relapsing Multiple Sclerosis, RMS, adult, MS
Medical subject headings: COVID-19

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

OfatumumabDrug
Also called OMB157
Ofatumumab 20 mg s.c. on days 1, 7, 14, week 4 and every 4 weeks thereafter

Study groups in NCT04869358
Study group	Role	What they receive
Cohort 1a	Experimental	Patients received first SARS-CoV-2 vaccination within the study prior to starting ofatumumab treatment. Receives: Drug: Ofatumumab
Cohort 1b	Experimental	Patients had already completed initial vaccination cycle and received a booster vaccine within the study prior to starting ofatumumab treatment. Receives: Drug: Ofatumumab
Cohort 2a	Experimental	Patients who received their first SARS-CoV-2 vaccination within the study while already stable on ofatumumab treatment for at least 4 weeks (since the first dose). Receives: Drug: Ofatumumab
Cohort 2b	Experimental	Patients who had already completed their initial vaccination cycle and received a booster vaccine within the study while already stable on ofatumumab treatment for at least 4 weeks (since the first dose). Receives: Drug: Ofatumumab

What is being measured

The primary outcome is the main question the study is designed to answer.

Percentage of Participants Having Established SARS-CoV-2-specific T Cells After Receiving a modRNA Vaccine
Participants who established SARS-CoV-2-specific T cells as defined by detection of SARS-CoV-2 reactive T-cells, measured by e.g. ELIspot assay from T-cells that were stimulated with SARS-CoV-2 peptide mix, either 1 month after second dose of vaccine or 1 month after booster vaccine in participants who received the respective vaccine before or after starting ofatumumab treatment.
Measured: 1 month after second dose of vaccine or booster vaccine

Secondary outcomes (4)

Percentage of Participants Who Maintained T-cell Response After Receiving a modRNA Vaccine
Participants who maintained detectable SARS-CoV-2 reactive T-cells (measured by e.g. ELIspot assay from T-cells that were stimulated with SARS-CoV-2 peptide mix) after second dose of vaccine or 6 and 12 months after booster vaccine in participants who received the vaccine before or after starting ofatumumab treatment. First booster vaccination was optional for cohorts 1a and 2a. In cohorts 1b and 2b the time points "Month 1 after Vacc" and "1 Month after booster" are identical.
Measured: At Week 1, Months 6, 12 and 18 after second dose of vaccine or 1 Month after 1st booster, 1 Month after 2nd booster
Increase in Specific T-cells After Receiving an modRNA Booster Vaccine
Patients having established SARS-CoV-2-specific T cells as defined by detection of SARS-CoV-2 reactive T-cells, measured by e.g. ELIspot assay from T-cells that were stimulated with SARS-CoV-2 peptide mix 1 month after booster vaccine in participants who received the respective vaccine before or after starting ofatumumab treatment. The fold change of SI from last value before booster to Month 1 is the ratio of SI at Month 1 divided by SI at last value before booster.
Measured: Last value before booster to 1 month after booster
Percentage of RMS Participants With Quantifiable Levels of SARS-CoV-2 Serum Functional Antibodies by Visits and Subcohorts (EAS)
Level of SARS-CoV-2 serum functional antibodies were measured by a central laboratory using a neutralizing antibody detection kit.
Measured: Baseline, Week 1 after Vacc, Month 1, 6, 12 after Vacc, 1 month after 1st booster, 1 month after 2nd booster
SARS-CoV-2 Specific CD4+ Effector Memory T-cells
Phenotypic description of the cellular immune response was performed at the central laboratory. T-cells were stimulated with SARS-CoV-2 peptide mix and analyzed for IFNg- and IL4 secretion using FACS analysis.
Measured: Baseline, Months 1 ,6, 12 and 18 after vaccinationse of vaccine or 1,6 and 12 months after booster vaccine

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

27 May 202113 Jun 2023

First posted3 May 2021
Study start27 May 2021
Primary completion10 May 2022
Study completion13 Jun 2023

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for Relapsing Multiple SclerosisStudies of the same condition, open and under way.
More trials run by Novartis PharmaceuticalsThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 4
Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Parallel groups
Masking: None (open label)
Enrolment: 34 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT04869358
Sponsor's protocol ID: COMB157GDE01
Acronym: KYRIOS
Status last verified: May 2025
First submitted: 29 Apr 2021
Last updated: 16 May 2025
Results posted: Yes, on ClinicalTrials.gov
FDA-regulated drug: No
FDA-regulated device: No
Individual data sharing: Yes: Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on https://www.clinicalstudydatarequest.com/.

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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All Relapsing Multiple Sclerosis trials

Study at a glance

From the registry record, last updated by the sponsor on 16 May 2025. Recruitment status is as the sponsor reported it: confirm with the study team.

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)
ClinicalTrials.gov ID: NCT04869358
Acronym / sponsor ID: KYRIOS / COMB157GDE01
Conditions: Relapsing Multiple Sclerosis
Keywords: COVID-19, SARS-CoV-2 mRNA vaccine, immune response, Ofatumumab, Relapsing Multiple Sclerosis, RMS, adult, MS
Phase: Phase 4
Study type: Interventional
Recruitment status: Completed
Enrolment: 34 participants (actual)
Lead sponsor: Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
Study start: 27 May 2021 (actual)
Primary completion: 10 May 2022 (actual)
Study completion: 13 Jun 2023 (actual)
First posted: 3 May 2021 (actual)
Results: Posted 11 Dec 2024

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

The first cohort was 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 was 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).

Cohort 1a - Patients received first SARS-CoV-2 vaccination within the study prior to starting ofatumumab treatment.

Cohort 1b - Patients had already completed initial vaccination cycle and received a booster vaccine within the study prior to starting ofatumumab treatment.

Cohort 2a - Patients who received their first SARS-CoV-2 vaccination within the study while already stable on ofatumumab treatment for at least 4 weeks (since the first dose).

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

Study design

Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 4

Arm	Type	Receives
Cohort 1a	Experimental	Drug: OfatumumabPatients received first SARS-CoV-2 vaccination within the study prior to starting ofatumumab treatment.
Cohort 1b	Experimental	Drug: OfatumumabPatients had already completed initial vaccination cycle and received a booster vaccine within the study prior to starting ofatumumab treatment.
Cohort 2a	Experimental	Drug: OfatumumabPatients who received their first SARS-CoV-2 vaccination within the study while already stable on ofatumumab treatment for at least 4 weeks (since the first dose).
Cohort 2b	Experimental	Drug: OfatumumabPatients who had already completed their initial vaccination cycle and received a booster vaccine within the study while already stable on ofatumumab treatment for at least 4 weeks (since the first dose).

Who may qualify

Ages: 18 to 100 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (3 listed)

Relapsing Multiple Sclerosis (RMS) diagnosis
eligible for ofatumumab treatment
willing and eligible to receive SARS-CoV-2 mRNA vaccine

Key exclusion criteria (4 listed)

known prior or current COVID-19 infection
previous treatment with BTK inhibitor or anti-CD20 therapy other than ofatumumab
no previous vaccination with a non-modRNA SARS-CoV-2 vaccine.
Other protocol-defined inclusion/exclusion criteria may apply

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
OfatumumabAlso: OMB157Ofatumumab 20 mg s.c. on days 1, 7, 14, week 4 and every 4 weeks thereafter	Drug	Cohort 1a, Cohort 1b, Cohort 2a, Cohort 2b

Primary outcome

Percentage of Participants Having Established SARS-CoV-2-specific T Cells After Receiving a modRNA Vaccine
Time frame: 1 month after second dose of vaccine or booster vaccine
Participants who established SARS-CoV-2-specific T cells as defined by detection of SARS-CoV-2 reactive T-cells, measured by e.g. ELIspot assay from T-cells that were stimulated with SARS-CoV-2 peptide mix, either 1 month after second dose of vaccine or 1 month after booster vaccine in participants who received the respective vaccine before or after starting ofatumumab treatment.

4 secondary outcomes

Percentage of Participants Who Maintained T-cell Response After Receiving a modRNA Vaccine
Time frame: At Week 1, Months 6, 12 and 18 after second dose of vaccine or 1 Month after 1st booster, 1 Month after 2nd booster
Increase in Specific T-cells After Receiving an modRNA Booster Vaccine
Time frame: Last value before booster to 1 month after booster
Percentage of RMS Participants With Quantifiable Levels of SARS-CoV-2 Serum Functional Antibodies by Visits and Subcohorts (EAS)
Time frame: Baseline, Week 1 after Vacc, Month 1, 6, 12 after Vacc, 1 month after 1st booster, 1 month after 2nd booster
SARS-CoV-2 Specific CD4+ Effector Memory T-cells
Time frame: Baseline, Months 1 ,6, 12 and 18 after vaccinationse of vaccine or 1,6 and 12 months after booster vaccine

Results and safety

Results posted to the registry on 11 Dec 2024, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Cohort 1a	6	5
Cohort 1b	8	8
Cohort 2a	5	5
Cohort 2b	15	15

Primary outcome: Percentage of Participants Having Established SARS-CoV-2-specific T Cells After Receiving a modRNA Vaccine

Time frame: 1 month after second dose of vaccine or booster vaccine. Number (95% Confidence Interval). Unit: percentage of participants

Measure	Cohort 1a n = 5	Cohort 1b n = 8	Cohort 2a n = 4	Cohort 2b n = 15	Total n = 32
Value	80.0 (28.4 to 99.5)	87.5 (47.3 to 99.7)	100.0 (39.8 to 100.0)	46.7 (21.3 to 73.4)	68.8 (50 to 83.9)

Population analysed: Efficacy and safety analysis sets

4 secondary outcomes are reported in the full results.

Adverse events

Time frame: Adverse events were reported from first dose of study treatment until the end of the treatment period plus an additional 30 day safety follow up period for a maximum time of 22 months.. Other adverse events reported at 2% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Cohort 1a	0 of 6 (0%)	6 of 6 (100%)	0 of 6
Cohort 1b	0 of 8 (0%)	6 of 8 (75%)	0 of 8
Cohort 2a	1 of 5 (20%)	5 of 5 (100%)	0 of 5
Cohort 2b	1 of 15 (6.7%)	15 of 15 (100%)	0 of 15

Limitations and caveats (from the sponsor): Immunophenotyping (outcome measure 5) was inconclusive due to low participant numbers.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 16 May 2025.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
A Plain Language Trial Summary is available on www.novctrd.comLink provided by the sponsor.
Individual participant dataSharing planned: Yes. Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on https://www.clinicalstudydatarequest.com/.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

The record lists no contact. Use the official record to reach the sponsor.

6 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Ofatumumab in people with Relapsing Multiple Sclerosis, run by Novartis Pharmaceuticals at 6 sites in Germany.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 3 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 16 May 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 6 sites in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 11 Dec 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Percentage of Participants Having Established SARS-CoV-2-specific T Cells After Receiving a modRNA Vaccine (time frame: 1 month after second dose of vaccine or booster vaccine). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04869358.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 May 2025.