Clinical trial NCT04926818: Efficacy and Safety of Ofatumumab and Siponimod Compared to Fingolimod in Pediatric Patients With Multiple Sclerosis
Official title: A 2-year Randomized, 3-arm, Double-blind, Non-inferiority Study Comparing the Efficacy and Safety of Ofatumumab and Siponimod Versus Fingolimod in Pediatric Patients With Multiple Sclerosis Followed by an Open-label Extension
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Multiple Sclerosis (MS)
Keywords: relapsing multiple sclerosis
pediatric
relapse
EDSS
ofatumumab
siponimod
fingolimod
RMS
MS
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2021-06-15
Enrollment: 129
Sex: ALL
Minimum age (years): 10
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Annualized relapse rate (ARR) in target pediatric participants
timeFrame: Baseline up to 24 months
Secondary outcomes:
measure: Annualized relapse rate (ARR) as compared to historical interferon β-1a data
timeFrame: Baseline up to 24 months
measure: Annualized T2 lesion rate
timeFrame: Baseline up to 24 months
measure: Neurofilament light chain (NfL) concentrations
timeFrame: Day 1, Months 3,6,12,18,24
measure: Plasma Concentrations of ofatumumab
timeFrame: Day 1, pre-dose for Day 7, Months 2,3,5,6,12,18,24
measure: Plasma Concentrations of siponimod
timeFrame: Day 1 (2,3,4,6 h), Day 3 (2,3,4,6 h), pre-dose for Months 1 (pre, 3h), 3,5,12
measure: Plasma Concentrations of siponimod metabolite (M17)
timeFrame: Pre-dose Month 3, 5 and Month 12
measure: Percentage of participants with anti-ofatumumab antibodies
timeFrame: Day 1, Pre-Dose Months 2,3,5,6,12,18,24
measure: Number of adverse events and serious adverse events
timeFrame: Baseline up approximately 66 months
Other outcomes:
Locations:
city: Little Rock
country: United States
facility: Arkansas Childrens Hosp Rsch Inst
state: Arkansas
city: Los Angeles
country: United States
facility: Childrens Hospital Los Angeles
state: California
city: Washington
country: United States
facility: Childrens National Medical Center
state: District of Columbia
city: Tampa
country: United States
facility: Axiom Clinical Research of Florida
state: Florida
city: Louisville
country: United States
facility: Uni of Louisville Clncl Trials Unit
state: Kentucky
city: Saint Louis
country: United States
facility: WA Uni School Of Med
state: Missouri
city: Philadelphia
country: United States
facility: Childrens Hospital of Philadelphia
state: Pennsylvania
city: Milwaukee
country: United States
facility: Medical College of Wisconsin
state: Wisconsin
city: Caba
country: Argentina
facility: Novartis Investigative Site
state: Buenos Aires
city: Parkville
country: Australia
facility: Novartis Investigative Site
state: Victoria
city: Wien
country: Austria
facility: Novartis Investigative Site
city: Esneux
country: Belgium
facility: Novartis Investigative Site
city: Gent
country: Belgium
facility: Novartis Investigative Site
city: Curitiba
country: Brazil
facility: Novartis Investigative Site
state: PR
city: Porto Alegre
country: Brazil
facility: Novartis Investigative Site
state: RS
city: Sao Paulo
country: Brazil
facility: Novartis Investigative Site
state: SP
city: Montreal
country: Canada
facility: Novartis Investigative Site
state: Quebec
city: Montreal
country: Canada
facility: Novartis Investigative Site
state: Quebec
city: Lo Barnechea
country: Chile
facility: Novartis Investigative Site
state: Santiago
city: Zagreb
country: Croatia
facility: Novartis Investigative Site
city: Tallinn
country: Estonia
facility: Novartis Investigative Site
city: Le Kremlin Bicetre
country: France
facility: Novartis Investigative Site
city: Montpellier
country: France
facility: Novartis Investigative Site
city: Strasbourg
country: France
facility: Novartis Investigative Site
city: Goettingen
country: Germany
facility: Novartis Investigative Site
state: Niedersachsen
city: Berlin
country: Germany
facility: Novartis Investigative Site
city: Bochum
country: Germany
facility: Novartis Investigative Site
city: Erlangen
country: Germany
facility: Novartis Investigative Site
city: Freiburg
country: Germany
facility: Novartis Investigative Site
city: Guatemala
country: Guatemala
facility: Novartis Investigative Site
city: New Delhi
country: India
facility: Novartis Investigative Site
state: Delhi
city: Lucknow
country: India
facility: Novartis Investigative Site
state: Uttar Pradesh
city: Kolkata
country: India
facility: Novartis Investigative Site
state: West Bengal
city: Petach Tikva
country: Israel
facility: Novartis Investigative Site
city: Roma
country: Italy
facility: Novartis Investigative Site
state: RM
city: Napoli
country: Italy
facility: Novartis Investigative Site
city: Riga
country: Latvia
facility: Novartis Investigative Site
city: Ciudad de Mexico
country: Mexico
facility: Novartis Investigative Site
state: Distrito Federal
city: Mexico
country: Mexico
facility: Novartis Investigative Site
state: Distrito Federal
city: Gdansk
country: Poland
facility: Novartis Investigative Site
city: Lodz
country: Poland
facility: Novartis Investigative Site
city: Poznan
country: Poland
facility: Novartis Investigative Site
city: Warsaw
country: Poland
facility: Novartis Investigative Site
city: Coimbra
country: Portugal
facility: Novartis Investigative Site
city: Lisboa
country: Portugal
facility: Novartis Investigative Site
city: Belgrade
country: Serbia
facility: Novartis Investigative Site
city: Bratislava
country: Slovakia
facility: Novartis Investigative Site
city: Sevilla
country: Spain
facility: Novartis Investigative Site
state: Andalucia
city: Baracaldo
country: Spain
facility: Novartis Investigative Site
state: Vizcaya
city: Tainan
country: Taiwan
facility: Novartis Investigative Site
city: Taipei
country: Taiwan
facility: Novartis Investigative Site
city: Istanbul
country: Turkey
facility: Novartis Investigative Site
state: TUR
city: Izmir
country: Turkey
facility: Novartis Investigative Site
city: Kocaeli
country: Turkey
facility: Novartis Investigative Site
city: Samsun
country: Turkey
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References: