Multiple Sclerosis (MS)Phase 3NEOSNCT04926818
Efficacy and Safety of Ofatumumab and Siponimod Compared to Fingolimod in Pediatric Patients With Multiple Sclerosis
A Phase 3 study testing Fingolimod, Ofatumumab and Siponimod in people with Multiple Sclerosis (MS), run by Novartis Pharmaceuticals at 51 sites in 25 countries.
Trial summary
Efficacy and safety of ofatumumab and siponimod compared to fingolimod in pediatric patients with multiple sclerosis Read more about this study
- Who is it for?
- Ages 10 to 17 years
- Conditions the study is for
- Multiple Sclerosis (MS)
- What is being tested?
- Fingolimod, Ofatumumab and Siponimod
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 129 participants
- Where
- 51 sitesin 25 countries
- Study dates
- 5 Oct 2021to 28 Feb 2031
- Phase
- Phase 3
- Are there results?
- Not yet: the study is under way
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 10 to 17 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Between 10 to <18 years of age (i.e., have not yet had their 18th birthday) at randomization
- Diagnosis of multiple sclerosis
- EDSS score of 0 to 5.5, inclusive
- At least one MS relapse/attack during the previous year or two MS relapses in the previous two years prior or evidence of one or more new T2 lesions within 12 months
Who cannot join
- Participants with progressive MS
- Participants with an active, chronic disease of the immune system other than MS
- Participants meeting the definition of ADEM
- Participants with severe cardiac disease or significant findings on the screening ECG.
- Participants with severe renal insufficiency
Trial locations and contacts
51 sites in 25 countries.
51 sites in 25 countries
United States6 sites
Arkansas Childrens Hosp Rsch Inst
Little Rock, Arkansas, 72202
Childrens Hospital Los Angeles
Los Angeles, California, 90027
Medical College of Wisconsin
Milwaukee, Wisconsin, 53226
Childrens Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104 4399
Axiom Clinical Research of Florida
Tampa, Florida, 33609
Childrens National Medical Center
Washington D.C., District of Columbia, 20010
Poland4 sites
Novartis Investigative Site
Gdansk, 80-214
Novartis Investigative Site
Lodz, 93-338
Novartis Investigative Site
Poznan, 60-355
Novartis Investigative Site
Warsaw, 04-730
Turkey (Türkiye)4 sites
Novartis Investigative Site
Istanbul, Fatih, 34098
Novartis Investigative Site
Izmir, Karsiyaka, 35575
Novartis Investigative Site
Kocaeli, 41380
Novartis Investigative Site
Samsun, Atakum, 55200
Brazil3 sites
Novartis Investigative Site
Curitiba, Paraná, 81210-310
Novartis Investigative Site
Porto Alegre, Rio Grande do Sul, 90430-001
Novartis Investigative Site
São Paulo, São Paulo, 05403-000
France3 sites
Novartis Investigative Site
Le Kremlin-Bicêtre, 94275
Novartis Investigative Site
Montpellier, 34090
Novartis Investigative Site
Strasbourg, 67000
Germany3 sites
Novartis Investigative Site
Bochum, 44791
Novartis Investigative Site
Freiburg im Breisgau, Baden-Wurttemberg, 79106
Novartis Investigative Site
Göttingen, Lower Saxony, 37075
India3 sites
Novartis Investigative Site
Kolkata, West Bengal, 700017
Novartis Investigative Site
Lucknow, Uttar Pradesh, 226014
Novartis Investigative Site
New Delhi, National Capital Territory of Delhi, 110017
Belgium2 sites
Novartis Investigative Site
Esneux, 4130
Novartis Investigative Site
Ghent, 9000
Canada2 sites
Novartis Investigative Site
Montreal, Quebec, H3A 2B4
Novartis Investigative Site
Montreal, Quebec, H3T 1C5
Italy2 sites
Novartis Investigative Site
Naples, 80131
Novartis Investigative Site
Roma, RM, 00165
Mexico2 sites
Novartis Investigative Site
Mexico City, Mexico City, 06700
Novartis Investigative Site
Mexico City, Mexico City, 06720
Portugal2 sites
Novartis Investigative Site
Coimbra, 3000-602
Novartis Investigative Site
Lisbon, 1169-050
Spain2 sites
Novartis Investigative Site
Barakaldo, Vizcaya, 48903
Novartis Investigative Site
Seville, 41009
Taiwan2 sites
Novartis Investigative Site
Tainan, 704302
Novartis Investigative Site
Taipei, 10002
Chile1 site
Novartis Investigative Site
Lo Barnechea, Santiago Metropolitan, 7691236
About this study
Official title: A 2-year Randomized, 3-arm, Double-blind, Non-inferiority Study Comparing the Efficacy and Safety of Ofatumumab and Siponimod Versus Fingolimod in Pediatric Patients With Multiple Sclerosis Followed by an Open-label Extension
Efficacy and safety of ofatumumab and siponimod compared to fingolimod in pediatric patients with multiple sclerosis
Read the detailed description
The study is divided into a Core Part and Extension Part. The Core Part is a 24-month, double-blind, triple dummy, randomized, 3-arm active-controlled in children/adolescent patients aged 10-17 years old with Multiple Sclerosis (MS). The Extension Part is 60-month (5 year) open label (except for first 12 weeks transition which will remain double-blind) treatment for patients who complete the Core Part of the study and meet all inclusion/exclusion criteria. The targeted enrollment is 120 participants with multiple sclerosis which will include at least 5 participants with body weight (BW) ≤40 kg and at least 5 participants with age 10 to 12 years in each of the ofatumumab and siponimod arms. There is a minimum 6 month follow up period for all participants (core and extension). Total duration of the study could be up to 7 years.
- Conditions
- Multiple Sclerosis (MS)
- Being tested
- Fingolimod, Ofatumumab, Siponimod, Fingolimod placebo, Siponimod placebo
- Keywords
- relapsing multiple sclerosis, pediatric, relapse, EDSS, ofatumumab, siponimod, fingolimod, RMS, MS
- Medical subject headings
- Multiple Sclerosis, Recurrence
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
FingolimodDrug
Also called FTY720
Fingolimod capsule administered orally once daily at a dose of either 0.5 mg or 0.25 mg (depending on patient's body weight).
OfatumumabDrug
Also called OMB157
Ofatumumab as a solution for injection in an autoinjector containing 20 mg ofatumumab (50 mg/mL, 0.4 mL content) for subcutaneous administration. A loading dose at Day1, Day 7 and Day 14 and then injections every 4 weeks/ 6 weeks (depending on patient's body weight).
SiponimodDrug
Also called BAF312
Siponimod tablet administered orally once daily. Titration period, Day 1 to Day 6, first dose is either 0.1 mg or 0.25 mg up to daily dose of either 0.5 mg, 1 mg or 2 mg (depending on CYP2C9 genotype and body weight).
Fingolimod placeboOther
Fingolimod matching placebo capsule
Siponimod placeboOther
Siponimod matching placebo tablet
Ofatumumab placeboOther
Ofatumumab matching placebo autoinjector
| Study group | Role | What they receive |
|---|---|---|
| ofatumumab - 20 mg injection/ placebo | Experimental | Ofatumumab as a solution for injection in an autoinjector containing 20 mg ofatumumab (50 mg/mL, 0.4 mL content) for subcutaneous administration. A loading dose at Day1, Day 7 and Day 14 and then injections every 4 weeks/ 6 weeks (depending on patient's body weight). Receives: Drug: Ofatumumab; Other: Ofatumumab placebo |
| siponimod - 0.5 mg, 1 mg or 2 mg/ placebo | Experimental | Siponimod tablet administered orally once daily. Titration period, Day 1 to Day 6, first dose is either 0.1 mg or 0.25 mg up to daily dose of either 0.5 mg, 1 mg or 2 mg (depending on CYP2C9 genotype and body weight). Receives: Drug: Siponimod; Other: Siponimod placebo |
| fingolimod - 0.5 mg or 0.25 mg/ placebo | Active comparator | Fingolimod capsule administered orally once daily at a dose of either 0.5 mg or 0.25 mg (depending on patient's body weight). Receives: Drug: Fingolimod; Other: Fingolimod placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Annualized relapse rate (ARR) in target pediatric participants
Frequency of relapses assessed by the annualized relapse rate (ARR). The ARR is defined as the average number of confirmed relapses per year (total number of confirmed relapses divided by the total days in the study multiplied by 365.25).
Measured: Baseline up to 24 months
Secondary outcomes (8)
Annualized relapse rate (ARR) as compared to historical interferon β-1a data
Frequency of relapses assessed by the annualized relapse rate (ARR) to historical interferon β-1a data. The ARR is defined as the average number of confirmed relapses per year. The historical data for interferon β-1a will derived from prior phase 3 studies.
Measured: Baseline up to 24 months
Annualized T2 lesion rate
Number of new/newly enlarged T2 lesions per year
Measured: Baseline up to 24 months
Neurofilament light chain (NfL) concentrations
Neurofilament light chain (NfL) concentration in serum of ofatumumab and/or siponimod versus fingolimod
Measured: Day 1, Months 3,6,12,18,24
Plasma Concentrations of ofatumumab
Ofatumumab plasma concentrations
Measured: Day 1, pre-dose for Day 7, Months 2,3,5,6,12,18,24
Plasma Concentrations of siponimod
Siponimod plasma concentrations
Measured: Day 1 (2,3,4,6 h), Day 3 (2,3,4,6 h), pre-dose for Months 1 (pre, 3h), 3,5,12
Plasma Concentrations of siponimod metabolite (M17)
Siponimod metabolite (M17) plasma concentration
Measured: Pre-dose Month 3, 5 and Month 12
Percentage of participants with anti-ofatumumab antibodies
Anti-ofatumumab antibodies to demonstrate immunogenicity of ofatumumab
Measured: Day 1, Pre-Dose Months 2,3,5,6,12,18,24
Number of adverse events and serious adverse events
Any clinically relevant finding that meets the criteria of an adverse event (as determined by the investigator) identified during the safety assessments (ECG, laboratory and ophthalmological data, pulmonary function tests and vital signs) will be reported as an adverse event
Measured: Baseline up approximately 66 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Jun 2021
- Study start5 Oct 2021
- Primary completion25 Mar 2026
- Study completion28 Feb 2031 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Multiple Sclerosis (MS)Studies 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 129 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novartis Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Novartis Pharmaceuticals, Study director, Novartis Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04926818
- Sponsor's protocol ID
- CBAF312D2301
- Acronym
- NEOS
- Status last verified
- May 2026
- First submitted
- 14 Jun 2021
- Last updated
- 14 May 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- 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 www.clinicalstudydatarequest
Study at a glance
From the registry record, last updated by the sponsor on 14 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A 2-year Randomized, 3-arm, Double-blind, Non-inferiority Study Comparing the Efficacy and Safety of Ofatumumab and Siponimod Versus Fingolimod in Pediatric Patients With Multiple Sclerosis Followed by an Open-label Extension
- ClinicalTrials.gov ID
- NCT04926818
- Acronym / sponsor ID
- NEOS / CBAF312D2301
- Conditions
- Multiple Sclerosis (MS)
- Keywords
- relapsing multiple sclerosis, pediatric, relapse, EDSS, ofatumumab, siponimod, fingolimod, RMS
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 129 participants (actual)
- Lead sponsor
- Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- 5 Oct 2021 (actual)
- Primary completion
- 25 Mar 2026 (actual)
- Study completion
- 28 Feb 2031 (estimated)
- First posted
- 15 Jun 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Efficacy and safety of ofatumumab and siponimod compared to fingolimod in pediatric patients with multiple sclerosis
Detailed description
The study is divided into a Core Part and Extension Part. The Core Part is a 24-month, double-blind, triple dummy, randomized, 3-arm active-controlled in children/adolescent patients aged 10-17 years old with Multiple Sclerosis (MS). The Extension Part is 60-month (5 year) open label (except for first 12 weeks transition which will remain double-blind) treatment for patients who complete the Core Part of the study and meet all inclusion/exclusion criteria. The targeted enrollment is 120 participants with multiple sclerosis which will include at least 5 participants with body weight (BW) ≤40 kg and at least 5 participants with age 10 to 12 years in each of the ofatumumab and siponimod arms. There is a minimum 6 month follow up period for all participants (core and extension). Total duration of the study could be up to 7 years.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| ofatumumab - 20 mg injection/ placebo | Experimental | Drug: Ofatumumab, Other: Ofatumumab placeboOfatumumab as a solution for injection in an autoinjector containing 20 mg ofatumumab (50 mg/mL, 0.4 mL content) for subcutaneous administration. A loading dose at Day1, Day 7 and Day 14 and then injections every 4 weeks/ 6 weeks (depending on patient's body weight). |
| siponimod - 0.5 mg, 1 mg or 2 mg/ placebo | Experimental | Drug: Siponimod, Other: Siponimod placeboSiponimod tablet administered orally once daily. Titration period, Day 1 to Day 6, first dose is either 0.1 mg or 0.25 mg up to daily dose of either 0.5 mg, 1 mg or 2 mg (depending on CYP2C9 genotype and body weight). |
| fingolimod - 0.5 mg or 0.25 mg/ placebo | Active comparator | Drug: Fingolimod, Other: Fingolimod placeboFingolimod capsule administered orally once daily at a dose of either 0.5 mg or 0.25 mg (depending on patient's body weight). |
Who may qualify
- Ages
- 10 to 17 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (4 listed)
- Between 10 to <18 years of age (i.e., have not yet had their 18th birthday) at randomization
- Diagnosis of multiple sclerosis
- EDSS score of 0 to 5.5, inclusive
- At least one MS relapse/attack during the previous year or two MS relapses in the previous two years prior or evidence of one or more new T2 lesions within 12 months
Key exclusion criteria (5 listed)
- Participants with progressive MS
- Participants with an active, chronic disease of the immune system other than MS
- Participants meeting the definition of ADEM
- Participants with severe cardiac disease or significant findings on the screening ECG.
- Participants with severe renal insufficiency
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 |
|---|---|---|
| FingolimodAlso: FTY720Fingolimod capsule administered orally once daily at a dose of either 0.5 mg or 0.25 mg (depending on patient's body weight). | Drug | fingolimod - 0.5 mg or 0.25 mg/ placebo |
| OfatumumabAlso: OMB157Ofatumumab as a solution for injection in an autoinjector containing 20 mg ofatumumab (50 mg/mL, 0.4 mL content) for subcutaneous administration. A loading dose at Day1, Day 7 and Day 14 and then injections every 4 weeks/ 6 weeks (depending on patient's body weight). | Drug | ofatumumab - 20 mg injection/ placebo |
| SiponimodAlso: BAF312Siponimod tablet administered orally once daily. Titration period, Day 1 to Day 6, first dose is either 0.1 mg or 0.25 mg up to daily dose of either 0.5 mg, 1 mg or 2 mg (depending on CYP2C9 genotype and body weight). | Drug | siponimod - 0.5 mg, 1 mg or 2 mg/ placebo |
| Fingolimod placeboFingolimod matching placebo capsule | Other | fingolimod - 0.5 mg or 0.25 mg/ placebo |
| Siponimod placeboSiponimod matching placebo tablet | Other | siponimod - 0.5 mg, 1 mg or 2 mg/ placebo |
| Ofatumumab placeboOfatumumab matching placebo autoinjector | Other | ofatumumab - 20 mg injection/ placebo |
Primary outcome
Annualized relapse rate (ARR) in target pediatric participants
Time frame: Baseline up to 24 months
Frequency of relapses assessed by the annualized relapse rate (ARR). The ARR is defined as the average number of confirmed relapses per year (total number of confirmed relapses divided by the total days in the study multiplied by 365.25).
8 secondary outcomes
Annualized relapse rate (ARR) as compared to historical interferon β-1a data
Time frame: Baseline up to 24 months
Annualized T2 lesion rate
Time frame: Baseline up to 24 months
Neurofilament light chain (NfL) concentrations
Time frame: Day 1, Months 3,6,12,18,24
Plasma Concentrations of ofatumumab
Time frame: Day 1, pre-dose for Day 7, Months 2,3,5,6,12,18,24
Plasma Concentrations of siponimod
Time frame: Day 1 (2,3,4,6 h), Day 3 (2,3,4,6 h), pre-dose for Months 1 (pre, 3h), 3,5,12
Plasma Concentrations of siponimod metabolite (M17)
Time frame: Pre-dose Month 3, 5 and Month 12
Percentage of participants with anti-ofatumumab antibodies
Time frame: Day 1, Pre-Dose Months 2,3,5,6,12,18,24
Number of adverse events and serious adverse events
Time frame: Baseline up approximately 66 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 May 2026.
- 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 www.clinicalstudydatarequest
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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.
Novartis Pharmaceuticals study director
Novartis Pharmaceuticals
51 sites in 25 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Fingolimod, Ofatumumab and Siponimod in people with Multiple Sclerosis (MS), run by Novartis Pharmaceuticals at 51 sites in 25 countries.
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 4 inclusion and 5 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: under way, not looking for participants, as of the sponsor's last update on 14 May 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 51 sites in United States, Poland, Turkey (Türkiye), Brazil, France and 20 more countries. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
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?
Annualized relapse rate (ARR) in target pediatric participants (time frame: Baseline up to 24 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 14 May 2026.