Multiple Sclerosis (MS)
Conditions
Keywords
relapsing multiple sclerosis, pediatric, relapse, EDSS, ofatumumab, siponimod, fingolimod, RMS, MS
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.
Interventions
DRUGFingolimod
Fingolimod capsule administered orally once daily at a dose of either 0.5 mg or 0.25 mg (depending on patient's body weight).
DRUGOfatumumab
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).
DRUGSiponimod
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).
OTHERFingolimod placebo
Fingolimod matching placebo capsule
OTHERSiponimod placebo
Siponimod matching placebo tablet
OTHEROfatumumab placebo
Ofatumumab matching placebo autoinjector
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
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.
Eligibility
Sex/Gender
ALL
Age
10 Years to 17 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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 |
| 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 |
Countries
Argentina, Australia, Austria, Belgium, Brazil, Canada, Chile, Croatia, Estonia, France, Germany, Guatemala, India, Israel, Italy, Latvia, Mexico, Poland, Portugal, Serbia, Slovakia, Spain, Taiwan, Turkey (Türkiye), United States
Contacts
STUDY_DIRECTORNovartis Pharmaceuticals
Novartis Pharmaceuticals
Outcome results
None listed