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

Phase 3Active Not RecruitingNCT04926818

Novartis Pharmaceuticals129 enrolled

Overview

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

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

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

129

Conditions

Multiple Sclerosis (MS)

Interventions

FingolimodDRUG

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

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

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).

Eligibility

Sex: ALLMin age: 10 YearsMax age: 17 Years

Medical Language ↔ Plain English

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

Locations (51)

Outcomes

Primary Outcomes

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).

Time frame: Baseline up to 24 months

Secondary Outcomes

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.

Time frame: Baseline up to 24 months

Annualized T2 lesion rate

Number of new/newly enlarged T2 lesions per year

Time frame: Baseline up to 24 months

Neurofilament light chain (NfL) concentrations

Neurofilament light chain (NfL) concentration in serum of ofatumumab and/or siponimod versus fingolimod

Time frame: Day 1, Months 3,6,12,18,24

Plasma Concentrations of ofatumumab

Ofatumumab plasma concentrations

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

Plasma Concentrations of siponimod

Siponimod plasma concentrations

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)

Data from ClinicalTrials.gov

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Arkansas Childrens Hosp Rsch Inst

Little Rock, Arkansas, United States

Childrens Hospital Los Angeles

Los Angeles, California, United States

Childrens National Medical Center

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

Axiom Clinical Research of Florida

Tampa, Florida, United States

Childrens Hospital of Philadelphia

Philadelphia, Pennsylvania, United States

Medical College of Wisconsin

Milwaukee, Wisconsin, United States

Novartis Investigative Site

CABA, Argentina

Novartis Investigative Site

Parkville, Victoria, Australia

Novartis Investigative Site

Vienna, Austria

Novartis Investigative Site

Esneux, Belgium

...and 41 more locations