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

NCT04926818 | Active Not Recruiting Phase 3 DMC FDA Drug

• 1 other identifier: CBAF312D2301
• Study Type: interventional
• Target: 129
• Locations: 23 countries
• Sites: 48

Brief Summary

Efficacy and safety of ofatumumab and siponimod compared to fingolimod in pediatric patients with multiple sclerosis

Conditions

Multiple Sclerosis (MS)

Keywords

relapsing multiple sclerosis; pediatric; relapse; EDSS; ofatumumab; siponimod; fingolimod; RMS; MS

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (8)

• Annualized relapse rate (ARR) as compared to historical interferon β-1a data

  Baseline up to 24 months

• Annualized T2 lesion rate

  Baseline up to 24 months

• Neurofilament light chain (NfL) concentrations

  Day 1, Months 3,6,12,18,24

• Plasma Concentrations of ofatumumab

  Day 1, pre-dose for Day 7, Months 2,3,5,6,12,18,24

• Plasma Concentrations of siponimod

  Day 1 (2,3,4,6 h), Day 3 (2,3,4,6 h), pre-dose for Months 1 (pre, 3h), 3,5,12

Study Arms (3)

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).

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).

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).

Drug: Fingolimod; Other: Fingolimod placebo

Interventions

Fingolimod DRUG

Fingolimod capsule administered orally once daily at a dose of either 0.5 mg or 0.25 mg (depending on patient's body weight).

Also known as: FTY720

fingolimod - 0.5 mg or 0.25 mg/ placebo

Ofatumumab DRUG

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).

Also known as: OMB157

ofatumumab - 20 mg injection/ placebo

Siponimod DRUG

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).

Also known as: BAF312

siponimod - 0.5 mg, 1 mg or 2 mg/ placebo

Fingolimod placebo OTHER

Fingolimod matching placebo capsule

fingolimod - 0.5 mg or 0.25 mg/ placebo

Siponimod placebo OTHER

Siponimod matching placebo tablet

siponimod - 0.5 mg, 1 mg or 2 mg/ placebo

Ofatumumab placebo OTHER

Ofatumumab matching placebo autoinjector

ofatumumab - 20 mg injection/ placebo

Eligibility Criteria

• Age: 10 Years - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (51)

Arkansas Childrens Hosp Rsch Inst

Little Rock, Arkansas, 72202, United States

Location

Childrens Hospital Los Angeles

Los Angeles, California, 90027, United States

Location

Childrens National Medical Center

Washington D.C., District of Columbia, 20010, United States

Location

Axiom Clinical Research of Florida

Tampa, Florida, 33609, United States

Location

Childrens Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104 4399, United States

Location

Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

Novartis Investigative Site

CABA, C1181ACH, Argentina

Location

Novartis Investigative Site

Parkville, Victoria, 3052, Australia

Location

Novartis Investigative Site

Vienna, 1090, Austria

Location

Novartis Investigative Site

Esneux, 4130, Belgium

Location

Novartis Investigative Site

Ghent, 9000, Belgium

Location

Novartis Investigative Site

Curitiba, Paraná, 81210-310, Brazil

Location

Novartis Investigative Site

Porto Alegre, Rio Grande do Sul, 90430-001, Brazil

Location

Novartis Investigative Site

São Paulo, São Paulo, 05403-000, Brazil

Location

Novartis Investigative Site

Montreal, Quebec, H3A 2B4, Canada

Location

Novartis Investigative Site

Montreal, Quebec, H3T 1C5, Canada

Location

Novartis Investigative Site

Lo Barnechea, Santiago Metropolitan, 7691236, Chile

Location

Novartis Investigative Site

Zagreb, 10000, Croatia

Location

Novartis Investigative Site

Tallinn, 11315, Estonia

Location

Novartis Investigative Site

Le Kremlin-Bicêtre, 94275, France

Location

Novartis Investigative Site

Montpellier, 34090, France

Location

Novartis Investigative Site

Strasbourg, 67000, France

Location

Novartis Investigative Site

Freiburg im Breisgau, Baden-Wurttemberg, 79106, Germany

Location

Novartis Investigative Site

Göttingen, Lower Saxony, 37075, Germany

Location

Novartis Investigative Site

Bochum, 44791, Germany

Location

Novartis Investigative Site

Guatemala City, 01015, Guatemala

Location

Novartis Investigative Site

New Delhi, National Capital Territory of Delhi, 110017, India

Location

Novartis Investigative Site

Lucknow, Uttar Pradesh, 226014, India

Location

Novartis Investigative Site

Kolkata, West Bengal, 700017, India

Location

Novartis Investigative Site

Petah Tikva, 4920235, Israel

Location

Novartis Investigative Site

Roma, RM, 00165, Italy

Location

Novartis Investigative Site

Naples, 80131, Italy

Location

Novartis Investigative Site

Riga, LV-1004, Latvia

Location

Novartis Investigative Site

Mexico City, Mexico City, 06700, Mexico

Location

Novartis Investigative Site

Mexico City, Mexico City, 06720, Mexico

Location

Novartis Investigative Site

Gdansk, 80-214, Poland

Location

Novartis Investigative Site

Lodz, 93-338, Poland

Location

Novartis Investigative Site

Poznan, 60-355, Poland

Location

Novartis Investigative Site

Warsaw, 04-730, Poland

Location

Novartis Investigative Site

Coimbra, 3000-602, Portugal

Location

Novartis Investigative Site

Lisbon, 1169-050, Portugal

Location

Novartis Investigative Site

Belgrade, 11000, Serbia

Location

Novartis Investigative Site

Bratislava, 833 40, Slovakia

Location

Novartis Investigative Site

Barakaldo, Vizcaya, 48903, Spain

Location

Novartis Investigative Site

Seville, 41009, Spain

Location

Novartis Investigative Site

Tainan, 704302, Taiwan

Location

Novartis Investigative Site

Taipei, 10002, Taiwan

Location

Novartis Investigative Site

Samsun, Atakum, 55200, Turkey (Türkiye)

Location

Novartis Investigative Site

Istanbul, Fatih, 34098, Turkey (Türkiye)

Location

Novartis Investigative Site

Izmir, Karsiyaka, 35575, Turkey (Türkiye)

Location

Novartis Investigative Site

Kocaeli, 41380, Turkey (Türkiye)

Location

MeSH Terms

Conditions

Multiple Sclerosis; Recurrence

Interventions

Fingolimod Hydrochloride; ofatumumab; siponimod

Condition Hierarchy (Ancestors)

Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Sphingosine; Amino Alcohols; Alcohols; Organic Chemicals; Propylene Glycols; Glycols; Amines

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: The core part of the study and the first 12 weeks of the extension period (transition) will be double-blinded and the remainder of the extension period will be open label.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 14, 2021
• First Posted: June 15, 2021
• Study Start: October 5, 2021
• Primary Completion: March 25, 2026
• Study Completion (Estimated): February 28, 2031
• Last Updated: April 29, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share

Locations

IN (3); BE (2); AR (1); BR (3); TW (2); TU (4); PL (4); GU (1); SL (1); ME (2); CA (2); LA (1); IL (1); AU (1); SE (1); US (6); CR (1); ES (1); DE (3); PT (2); IT (2); CL (1); FR (3)