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

Sponsor

Novartis Pharmaceuticals (Industry)

Overall Status

Recruiting

CT.gov ID

NCT04926818

Collaborator

(none)

180

Enrollment

Locations

Arms

91.9

Anticipated Duration (Months)

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Multiple Sclerosis (MS)	Drug: Fingolimod Drug: Ofatumumab Drug: Siponimod Other: Fingolimod placebo Other: Siponimod placebo Other: Ofatumumab placebo	Phase 3

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 180 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 Design

Study Type:

Interventional

Anticipated Enrollment :

180 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, 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.

Primary Purpose:

Treatment

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

Actual Study Start Date :

Oct 5, 2021

Anticipated Primary Completion Date :

Oct 1, 2026

Anticipated Study Completion Date :

Jun 1, 2029

Arms and Interventions

Arm	Intervention/Treatment
Experimental: ofatumumab - 20 mg injection/ placebo 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).	Drug: 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). Other Names: OMB157 Other: Ofatumumab placebo Ofatumumab matching placebo autoinjector
Experimental: siponimod - 0.5 mg, 1 mg or 2 mg/ placebo 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).	Drug: 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 Names: BAF312 Other: Siponimod placebo Siponimod matching placebo tablet
Active Comparator: fingolimod - 0.5 mg or 0.25 mg/ placebo Fingolimod capsule administered orally once daily at a dose of either 0.5 mg or 0.25 mg (depending on patient's body weight).	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). Other Names: FTY720 Other: Fingolimod placebo Fingolimod matching placebo capsule

Arm

Intervention/Treatment

Experimental: ofatumumab - 20 mg injection/ placebo

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).

Drug: Ofatumumab

Other Names:

OMB157

Other: Ofatumumab placebo

Ofatumumab matching placebo autoinjector

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

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).

Drug: Siponimod

Other Names:

BAF312

Other: Siponimod placebo

Siponimod matching placebo tablet

Active Comparator: fingolimod - 0.5 mg or 0.25 mg/ placebo

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

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).

Other Names:

FTY720

Other: Fingolimod placebo

Fingolimod matching placebo capsule

Outcome Measures

Primary Outcome Measures

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 Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

10 Years to 17 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Between 10 to <18 years of age (i.e., have not yet had their 18th birthday) at randomization
Diagnosis of multiple sclerosis
EDSS score of 0 to 5.5, inclusive
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:

Participants with progressive MS
Participants with an active, chronic disease of the immune system other than MS
Participants meeting the definition of ADEM
Participants with severe cardiac disease or significant findings on the screening ECG.
Participants with severe renal insufficiency

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Novartis Investigative Site	Little Rock	Arkansas	United States	72202
2	Novartis Investigative Site	Los Angeles	California	United States	90027
3	Novartis Investigative Site	San Diego	California	United States	92103
4	Novartis Investigative Site	Tampa	Florida	United States	33609
5	Novartis Investigative Site	Atlanta	Georgia	United States	30329
6	Novartis Investigative Site	Portland	Oregon	United States	97225
7	Novartis Investigative Site	Salt Lake City	Utah	United States	84132
8	Novartis Investigative Site	Parkville	Victoria	Australia	3052
9	Novartis Investigative Site	Vienna		Austria	1090
10	Novartis Investigative Site	Esneux		Belgium	4130
11	Novartis Investigative Site	Gent		Belgium	9000
12	Novartis Investigative Site	Porto Alegre	RS	Brazil	90430-001
13	Novartis Investigative Site	Montreal	Quebec	Canada	H3A 2B4
14	Novartis Investigative Site	Zagreb		Croatia
15	Novartis Investigative Site	Tallinn		Estonia	11315
16	Novartis Investigative Site	Le Kremlin Bicetre		France	94275
17	Novartis Investigative Site	Montpellier		France	34295
18	Novartis Investigative Site	Strasbourg		France	67098
19	Novartis Investigative Site	Erlangen		Germany	91054
20	Novartis Investigative Site	Gottingen		Germany	37075
21	Novartis Investigative Site	Guatemala		Guatemala	01015
22	Novartis Investigative Site	New Delhi	Delhi	India	110 060
23	Novartis Investigative Site	New Delhi	Delhi	India	110017
24	Novartis Investigative Site	Lucknow	Uttar Pradesh	India	226014
25	Novartis Investigative Site	Kolkata	West Bengal	India	700017
26	Novartis Investigative Site	Milano	MI	Italy	20132
27	Novartis Investigative Site	Napoli		Italy	80131
28	Novartis Investigative Site	Riga		Latvia	LV-1004
29	Novartis Investigative Site	Ciudad de Mexico	Distrito Federal	Mexico	06700
30	Novartis Investigative Site	Chihuahua		Mexico	31203
31	Novartis Investigative Site	Gdansk		Poland	80 952
32	Novartis Investigative Site	Lodz		Poland	93-338
33	Novartis Investigative Site	Poznan		Poland	60-355
34	Novartis Investigative Site	Warsaw		Poland	04 730
35	Novartis Investigative Site	Coimbra		Portugal	3000-602
36	Novartis Investigative Site	Lisboa		Portugal	1169-050
37	Novartis Investigative Site	St Petersburg		Russian Federation	190000
38	Novartis Investigative Site	Bratislava		Slovakia	833 40
39	Novartis Investigative Site	Sevilla	Andalucia	Spain	41009
40	Novartis Investigative Site	Baracaldo	Vizcaya	Spain	48903
41	Novartis Investigative Site	Taipei		Taiwan	10002
42	Novartis Investigative Site	Istanbul	TUR	Turkey	34098
43	Novartis Investigative Site	Izmir		Turkey	35340
44	Novartis Investigative Site	Kocaeli		Turkey	41380
45	Novartis Investigative Site	Samsun		Turkey	55139