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

Novartis

Status and phase: Enrolling; Phase 3

Conditions: Multiple Sclerosis (MS)

Treatments: Other: Ofatumumab placebo; Drug: Siponimod; Drug: Ofatumumab; Other: Fingolimod placebo; Other: Siponimod placebo; Drug: Fingolimod

Study type: Interventional

Funder types: Industry

Identifiers

NCT04926818

CBAF312D2301

Details and patient eligibility

About

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

Full 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.

Enrollment: 120 estimated patients

Sex: All

Ages: 10 to 17 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

---

120 participants in 3 patient groups

ofatumumab - 20 mg injection/ placebo

Experimental group

Description:

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).

Treatment:

Drug: Ofatumumab

Other: Ofatumumab placebo

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

Experimental group

Description:

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).

Treatment:

Other: Siponimod placebo

Drug: Siponimod

fingolimod - 0.5 mg or 0.25 mg/ placebo

Active Comparator group

Description:

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

Treatment:

Drug: Fingolimod

Other: Fingolimod placebo