Efficacy and Safety of Ofatumumab and Siponimod Compared to Fingolimod in Pediatric Patients With Multiple Sclerosis (NEOS)

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

Study Overview

• Status: Active, not recruiting
• Conditions: Multiple Sclerosis (MS)
• Intervention / Treatment: Drug: Ofatumumab; Other: Ofatumumab placebo; Drug: Siponimod; Other: Siponimod placebo; Drug: Fingolimod; Other: Fingolimod placebo

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 Type: Interventional
• Enrollment (Actual): 129
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • CABA, Argentina, C1181ACH
    • Novartis Investigative Site
• Australia
  • Victoria
    • Parkville, Victoria, Australia, 3052
      • Novartis Investigative Site
• Austria
  • Vienna, Austria, 1090
    • Novartis Investigative Site
• Belgium
  • Esneux, Belgium, 4130
    • Novartis Investigative Site
  • Ghent, Belgium, 9000
    • Novartis Investigative Site
• Brazil
  • Paraná
    • Curitiba, Paraná, Brazil, 81210-310
      • Novartis Investigative Site
  • Rio Grande do Sul
    • Porto Alegre, Rio Grande do Sul, Brazil, 90430-001
      • Novartis Investigative Site
  • São Paulo
    • São Paulo, São Paulo, Brazil, 05403-000
      • Novartis Investigative Site
• Canada
  • Quebec
    • Montreal, Quebec, Canada, H3T 1C5
      • Novartis Investigative Site
    • Montreal, Quebec, Canada, H3A 2B4
      • Novartis Investigative Site
• Chile
  • Santiago Metropolitan
    • Lo Barnechea, Santiago Metropolitan, Chile, 7691236
      • Novartis Investigative Site
• Croatia
  • Zagreb, Croatia, 10000
    • Novartis Investigative Site
• Estonia
  • Tallinn, Estonia, 11315
    • Novartis Investigative Site
• France
  • Le Kremlin-Bicêtre, France, 94275
    • Novartis Investigative Site
  • Montpellier, France, 34090
    • Novartis Investigative Site
  • Strasbourg, France, 67000
    • Novartis Investigative Site
• Germany
  • Bochum, Germany, 44791
    • Novartis Investigative Site
  • Baden-Wurttemberg
    • Freiburg im Breisgau, Baden-Wurttemberg, Germany, 79106
      • Novartis Investigative Site
  • Lower Saxony
    • Göttingen, Lower Saxony, Germany, 37075
      • Novartis Investigative Site
• Guatemala
  • Guatemala City, Guatemala, 01015
    • Novartis Investigative Site
• India
  • National Capital Territory of Delhi
    • New Delhi, National Capital Territory of Delhi, India, 110017
      • Novartis Investigative Site
  • Uttar Pradesh
    • Lucknow, Uttar Pradesh, India, 226014
      • Novartis Investigative Site
  • West Bengal
    • Kolkata, West Bengal, India, 700017
      • Novartis Investigative Site
• Israel
  • Petah Tikva, Israel, 4920235
    • Novartis Investigative Site
• Italy
  • Naples, Italy, 80131
    • Novartis Investigative Site
  • RM
    • Roma, RM, Italy, 00165
      • Novartis Investigative Site
• Latvia
  • Riga, Latvia, LV-1004
    • Novartis Investigative Site
• Mexico
  • Mexico City
    • Mexico City, Mexico City, Mexico, 06700
      • Novartis Investigative Site
    • Mexico City, Mexico City, Mexico, 06720
      • Novartis Investigative Site
• Poland
  • Gdansk, Poland, 80-214
    • Novartis Investigative Site
  • Lodz, Poland, 93-338
    • Novartis Investigative Site
  • Poznan, Poland, 60-355
    • Novartis Investigative Site
  • Warsaw, Poland, 04-730
    • Novartis Investigative Site
• Portugal
  • Coimbra, Portugal, 3000-602
    • Novartis Investigative Site
  • Lisbon, Portugal, 1169-050
    • Novartis Investigative Site
• Serbia
  • Belgrade, Serbia, 11000
    • Novartis Investigative Site
• Slovakia
  • Bratislava, Slovakia, 833 40
    • Novartis Investigative Site
• Spain
  • Seville, Spain, 41009
    • Novartis Investigative Site
  • Vizcaya
    • Barakaldo, Vizcaya, Spain, 48903
      • Novartis Investigative Site
• Taiwan
  • Tainan, Taiwan, 704302
    • Novartis Investigative Site
  • Taipei, Taiwan, 10002
    • Novartis Investigative Site
• Turkey (Türkiye)
  • Kocaeli, Turkey (Türkiye), 41380
    • Novartis Investigative Site
  • Atakum
    • Samsun, Atakum, Turkey (Türkiye), 55200
      • Novartis Investigative Site
  • Fatih
    • Istanbul, Fatih, Turkey (Türkiye), 34098
      • Novartis Investigative Site
  • Karsiyaka
    • Izmir, Karsiyaka, Turkey (Türkiye), 35575
      • Novartis Investigative Site
• United States
  • Arkansas
    • Little Rock, Arkansas, United States, 72202
      • Arkansas Childrens Hosp Rsch Inst
  • California
    • Los Angeles, California, United States, 90027
      • Childrens Hospital Los Angeles
  • District of Columbia
    • Washington D.C., District of Columbia, United States, 20010
      • Childrens National Medical Center
  • Florida
    • Tampa, Florida, United States, 33609
      • Axiom Clinical Research of Florida
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104 4399
      • Childrens Hospital of Philadelphia
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Medical College of Wisconsin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 10 years to 17 years (Child)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Between 10 to <18 years of age (i.e., have not yet had their 18th birthday) at randomization
2. Diagnosis of multiple sclerosis
3. EDSS score of 0 to 5.5, inclusive
4. 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

Exclusion Criteria:

1. Participants with progressive MS
2. Participants with an active, chronic disease of the immune system other than MS
3. Participants meeting the definition of ADEM
4. Participants with severe cardiac disease or significant findings on the screening ECG.
5. Participants with severe renal insufficiency

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ofatumumab - 20 mg injection/ placebo; 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).	Drug: Ofatumumab; 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).; Other Names: OMB157; Other: Ofatumumab placebo; Ofatumumab matching placebo autoinjector
Experimental: siponimod - 0.5 mg, 1 mg or 2 mg/ placebo; 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).	Drug: Siponimod; 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).; Other Names: BAF312; Other: Siponimod placebo; Siponimod matching placebo tablet
Active Comparator: fingolimod - 0.5 mg or 0.25 mg/ placebo; Fingolimod 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; Fingolimod capsule administered orally once daily at a dose of either 0.5 mg or 0.25 mg (depending on patient's body weight).; Other Names: FTY720; Other: Fingolimod placebo; Fingolimod matching placebo capsule

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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).	Baseline up to 24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Baseline up to 24 months
Annualized T2 lesion rate	Number of new/newly enlarged T2 lesions per year	Baseline up to 24 months
Neurofilament light chain (NfL) concentrations	Neurofilament light chain (NfL) concentration in serum of ofatumumab and/or siponimod versus fingolimod	Day 1, Months 3,6,12,18,24
Plasma Concentrations of ofatumumab	Ofatumumab plasma concentrations	Day 1, pre-dose for Day 7, Months 2,3,5,6,12,18,24
Plasma Concentrations of siponimod	Siponimod plasma concentrations	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	Pre-dose Month 3, 5 and Month 12
Percentage of participants with anti-ofatumumab antibodies	Anti-ofatumumab antibodies to demonstrate immunogenicity of ofatumumab	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	Baseline up approximately 66 months

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals
• Investigators: Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): October 5, 2021
• Primary Completion (Actual): March 25, 2026
• Study Completion (Estimated): February 28, 2031

Study Registration Dates

• First Submitted: June 14, 2021
• First Submitted That Met QC Criteria: June 14, 2021
• First Posted (Actual): June 15, 2021

Study Record Updates

• Last Update Posted (Actual): May 14, 2026
• Last Update Submitted That Met QC Criteria: May 13, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: MS; relapse; pediatric; ofatumumab; EDSS; siponimod; RMS; relapsing multiple sclerosis; fingolimod
• Additional Relevant MeSH Terms: Nervous System Diseases; Pathologic Processes; Disease Attributes; Autoimmune Diseases; Immune System Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Pathological Conditions, Signs and Symptoms; Multiple Sclerosis; Recurrence; Organic Chemicals; Amines; Alcohols; Glycols; Amino Alcohols; Sphingosine; Propylene Glycols; Fingolimod Hydrochloride; ofatumumab; siponimod
• Other Study ID Numbers: CBAF312D2301

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

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

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No