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

Multiple Sclerosis (MS) Clinical Trial

— NEOS  

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04926818
• Other study ID #: CBAF312D2301
• Status: Recruiting
• Phase: Phase 3
• Start date: October 5, 2021
• Est. completion date: December 23, 2031

Study information

• Verified date: June 2024
• Source: Novartis
• Contact: Novartis Pharmaceuticals
• Phone: 1-888-669-6682
• Email: novartis.email[@]novartis.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 120
• Est. completion date: December 23, 2031
• Est. primary completion date: March 2, 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 10 Years to 17 Years

Eligibility

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

Related Conditions & MeSH terms

• Multiple Sclerosis
• Multiple Sclerosis (MS)
• Sclerosis

Intervention

Drug:
• 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).
• 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).
• 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).

Other:
• Fingolimod placebo
Fingolimod matching placebo capsule
• Siponimod placebo
Siponimod matching placebo tablet
• Ofatumumab placebo
Ofatumumab matching placebo autoinjector

Locations

Country	Name	City	State
Argentina	Novartis Investigative Site	Caba	Buenos Aires
Australia	Novartis Investigative Site	Parkville	Victoria
Austria	Novartis Investigative Site	Vienna
Belgium	Novartis Investigative Site	Esneux
Belgium	Novartis Investigative Site	Gent
Brazil	Novartis Investigative Site	Curitiba	PR
Brazil	Novartis Investigative Site	Porto Alegre	RS
Brazil	Novartis Investigative Site	Sao Paulo	SP
Canada	Novartis Investigative Site	Montreal	Quebec
Canada	Novartis Investigative Site	Montreal	Quebec
Canada	Novartis Investigative Site	Toronto	Ontario
Chile	Novartis Investigative Site	Lo Barnechea	Santiago
Croatia	Novartis Investigative Site	Zagreb
Estonia	Novartis Investigative Site	Tallinn
France	Novartis Investigative Site	Le Kremlin Bicetre
France	Novartis Investigative Site	Montpellier
France	Novartis Investigative Site	Strasbourg
Germany	Novartis Investigative Site	Berlin
Germany	Novartis Investigative Site	Bochum
Germany	Novartis Investigative Site	Erlangen
Germany	Novartis Investigative Site	Freiburg
Germany	Novartis Investigative Site	Gottingen
Guatemala	Novartis Investigative Site	Guatemala
India	Novartis Investigative Site	Kochi	Kerala
India	Novartis Investigative Site	Kolkata	West Bengal
India	Novartis Investigative Site	Lucknow	Uttar Pradesh
India	Novartis Investigative Site	New Delhi	Delhi
India	Novartis Investigative Site	New Delhi	Delhi
Israel	Novartis Investigative Site	Petach Tikva
Italy	Novartis Investigative Site	Milano	MI
Italy	Novartis Investigative Site	Napoli
Italy	Novartis Investigative Site	Roma	RM
Latvia	Novartis Investigative Site	Riga
Mexico	Novartis Investigative Site	Chihuahua
Mexico	Novartis Investigative Site	Ciudad de Mexico	Distrito Federal
Mexico	Novartis Investigative Site	Mexico	Distrito Federal
Poland	Novartis Investigative Site	Gdansk
Poland	Novartis Investigative Site	Lodz
Poland	Novartis Investigative Site	Poznan
Poland	Novartis Investigative Site	Warsaw
Portugal	Novartis Investigative Site	Coimbra
Portugal	Novartis Investigative Site	Lisboa
Romania	Novartis Investigative Site	Bucuresti
Russian Federation	Novartis Investigative Site	St Petersburg
Serbia	Novartis Investigative Site	Belgrade
Slovakia	Novartis Investigative Site	Bratislava
Spain	Novartis Investigative Site	Baracaldo	Vizcaya
Spain	Novartis Investigative Site	Madrid
Spain	Novartis Investigative Site	Oviedo	Asturias
Spain	Novartis Investigative Site	Sevilla	Andalucia
Taiwan	Novartis Investigative Site	Kaohsiung
Taiwan	Novartis Investigative Site	Tainan
Taiwan	Novartis Investigative Site	Taipei
Turkey	Novartis Investigative Site	Istanbul	TUR
Turkey	Novartis Investigative Site	Izmir
Turkey	Novartis Investigative Site	Izmir
Turkey	Novartis Investigative Site	Kocaeli
Turkey	Novartis Investigative Site	Samsun
United Kingdom	Novartis Investigative Site	London
United States	Childrens Healthcare of Atlanta .	Atlanta	Georgia
United States	University of Texas Southwestern Main Center	Dallas	Texas
United States	Arkansas Childrens Hosp Rsch Inst .	Little Rock	Arkansas
United States	Childrens Hospital Los Angeles .	Los Angeles	California
United States	Uni of Louisville Clncl Trials Unit Novak Center	Louisville	Kentucky
United States	Medical College of Wisconsin .	Milwaukee	Wisconsin
United States	West Virginia University Cardio	Morgantown	West Virginia
United States	Childrens Hospital of Philadelphia .	Philadelphia	Pennsylvania
United States	Providence St Vincent Med Center .	Portland	Oregon
United States	Mayo Clinic - Rochester	Rochester	Minnesota
United States	WA Uni School Of Med Main Center	Saint Louis	Missouri
United States	The University of Utah Health Image and Neurosciences	Salt Lake City	Utah
United States	University of California San Diego	San Diego	California
United States	Axiom Clinical Research of Florida	Tampa	Florida
United States	Childrens National Medical Center .	Washington	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Austria,  Belgium,  Brazil,  Canada,  Chile,  Croatia,  Estonia,  France,  Germany,  Guatemala,  India,  Israel,  Italy,  Latvia,  Mexico,  Poland,  Portugal,  Romania,  Russian Federation,  Serbia,  Slovakia,  Spain,  Taiwan,  Turkey,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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).	Baseline up to 24 months
Secondary	Annualized relapse rate (ARR) as compared to historical interferon ß-1a data	Frequency of relapses assessed by the annualized relapse rate (ARR) to historical interferon ß-1a data. The ARR is defined as the average number of confirmed relapses per year. The historical data for interferon ß-1a will derived from prior phase 3 studies.	Baseline up to 24 months
Secondary	Annualized T2 lesion rate	Number of new/newly enlarged T2 lesions per year	Baseline up to 24 months
Secondary	Neurofilament light chain (NfL) concentrations	Neurofilament light chain (NfL) concentration in serum of ofatumumab and/or siponimod versus fingolimod	Day 1, Months 3,6,12,18,24
Secondary	Plasma Concentrations of ofatumumab	Ofatumumab plasma concentrations	Day 1, pre-dose for Day 7, Months 2,3,5,6,12,18,24
Secondary	Plasma Concentrations of siponimod	Siponimod plasma concentrations	Day 1 (2,3,4,6 h), Day 3 (2,3,4,6 h), pre-dose for Months 1 (pre, 3h), 3,5,12
Secondary	Plasma Concentrations of siponimod metabolite (M17)	Siponimod metabolite (M17) plasma concentration	Pre-dose Month 3, 5 and Month 12
Secondary	Percentage of participants with anti-ofatumumab antibodies	Anti-ofatumumab antibodies to demonstrate immunogenicity of ofatumumab	Day 1, Pre-Dose Months 2,3,5,6,12,18,24
Secondary	Number of adverse events and serious adverse events	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	Baseline up approximately 66 months