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

Phase 3

Active, not recruiting

• Conditions: Multiple Sclerosis (MS)
• Interventions: Drug: Ofatumumab; Drug: Siponimod; Drug: Fingolimod; Other: Ofatumumab placebo; Other: Siponimod placebo; Other: Fingolimod placebo

• Registration Number: NCT04926818
• Lead Sponsor: Novartis Pharmaceuticals

Brief Summary

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 Timeline

• Study First Submitted: 2021-06-14
• Study First Submitted QC: 2021-06-14
• Study First Posted: 2021-06-15
• Study Start: 2021-10-05
• Status Verified: 2025-04
• Last Update Submitted: 2025-04-23
• Last Update Posted: 2025-04-24
• Primary Completion: 2027-03-02
• Study Completion: 2031-11-18

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 129

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
ofatumumab - 20 mg injection/ placebo	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).
ofatumumab - 20 mg injection/ placebo	Ofatumumab 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).
siponimod - 0.5 mg, 1 mg or 2 mg/ placebo	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).
siponimod - 0.5 mg, 1 mg or 2 mg/ placebo	Siponimod 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).
fingolimod - 0.5 mg or 0.25 mg/ placebo	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).
fingolimod - 0.5 mg or 0.25 mg/ placebo	Fingolimod 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).

Primary Outcome Measures

Name	Time	Method
Annualized relapse rate (ARR) in target pediatric participants	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).

Secondary Outcome Measures

Name	Time	Method
Annualized relapse rate (ARR) as compared to historical interferon β-1a data	Baseline up to 24 months	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.
Number of adverse events and serious adverse events	Baseline up approximately 66 months	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
Annualized T2 lesion rate	Baseline up to 24 months	Number of new/newly enlarged T2 lesions per year
Neurofilament light chain (NfL) concentrations	Day 1, Months 3,6,12,18,24	Neurofilament light chain (NfL) concentration in serum of ofatumumab and/or siponimod versus fingolimod
Plasma Concentrations of ofatumumab	Day 1, pre-dose for Day 7, Months 2,3,5,6,12,18,24	Ofatumumab plasma concentrations
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	Siponimod plasma concentrations
Plasma Concentrations of siponimod metabolite (M17)	Pre-dose Month 3, 5 and Month 12	Siponimod metabolite (M17) plasma concentration
Percentage of participants with anti-ofatumumab antibodies	Day 1, Pre-Dose Months 2,3,5,6,12,18,24	Anti-ofatumumab antibodies to demonstrate immunogenicity of ofatumumab

Trial Locations

Locations (9)

Novartis Investigative Site; 🇹🇷 Samsun, Turkey

Arkansas Childrens Hosp Rsch Inst; 🇺🇸 Little Rock, Arkansas, United States

Childrens Hospital Los Angeles; 🇺🇸 Los Angeles, California, United States

Childrens National Medical Center; 🇺🇸 Washington, District of Columbia, United States

Axiom Clinical Research of Florida; 🇺🇸 Tampa, Florida, United States

Uni of Louisville Clncl Trials Unit; 🇺🇸 Louisville, Kentucky, United States

WA Uni School Of Med; 🇺🇸 Saint Louis, Missouri, United States

Childrens Hospital of Philadelphia; 🇺🇸 Philadelphia, Pennsylvania, United States

Medical College of Wisconsin; 🇺🇸 Milwaukee, Wisconsin, United States