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

• Register: EUCTR
• Last refreshed on: 27 January 2025
• Main ID: EUCTR2020-002700-39-LV
• Date of registration: 28/07/2021
• Prospective Registration: Yes
• Primary sponsor: Novartis Pharma AG
• Public title: Efficacy and safety of ofatumumab and siponimod compared to fingolimod in pediatric patients with multiple sclerosis.
• Scientific 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. Additional PIP decision number: P/014/2021 - NEOS
• Date of first enrolment: 09/09/2021
• Target sample size: 95
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2020-002700-39
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: yes Placebo: no Other: no Number of treatment arms in the trial: 3
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

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

Contacts

• Name: Clinical Trial Information Desk
• Affiliation: SIA Novartis Baltics

• Name: Clinical Trial Information Desk
• Affiliation: SIA Novartis Baltics

Key inclusion & exclusion criteria

Inclusion criteria:
-Signed informed consent/assent must be obtained prior to participation in the study
-Between 10 to <18 years of age (i.e., have not yet had their 18th birthday) at randomization
-A diagnosis of MS as defined by the consensus definition for pediatric MS
-Expanded Disability Status Scale (EDSS) score of 0 to 5.5 (inclusive) at screening
-At least one MS relapse/attack during the previous year or two MS relapses in the previous two years prior to screening or evidence of one or more new T2 lesions compared to prior MRI conducted within 12 months prior to randomization (including screening MRI) or one or more Gd-enhancing
T1 lesions on MRI conducted within 12 months prior to randomization
-Other protocol-defined inclusion/exclusion criteria may apply
Are the trial subjects under 18? yes
Number of subjects for this age range: 180
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
-Participants with progressive MS
-Participants meeting the definition of ADEM
-Participants meeting criteria for neuromyelitis optica or tested positive for aquaporin 4 (AQP4) at Screening
-Participants tested positive for anti-MOG at Screening
-Participants with widespread and symmetric white matter alterations in the Screening MRI suggestive of other demyelinating disorders (e.g. metabolic disorders, mitochondrial disorders)
-Homozygosity for CYP2C9*3, or refusal to test for CYP2C9
-Participants with an active, chronic disease (or stable but treated with immune therapy) of the immune system other than MS (e.g. Sjögren’s disease, systemic lupus erythematosus) or with a known immunodeficiency syndrome (Acquired immunodeficiency syndrome (AIDS), hereditary immunodeficiency, drug-induced immunodeficiency ) or tested positive for HIV at Screening
-Participants with neurological symptoms consistent with progressive multifocal leukoencephalopathy (PML) or confirmed PML
-Participants diagnosed with macular edema during the Screening period -Participants with severe active systemic bacterial, viral or fungal infections, including tuberculosis
-Participants with any severe cardiac disease or significant findings on the screening ECG
Any history of malignancy of any organ system
-Participants treated with any of the listed medication as Exclusion Medication within defined timespan
-Positive results of screening period testing for serological markers for hepatitis A, B, C and E indicating acute or chronic infection
-Any other clinically significant laboratory assessment as determined by the Investigator (e.g. significant anemia, neutropenia, thrombocytopenia, signs of impaired bone marrow function
-Have received any live or live-attenuated vaccines (including for varicellazoster virus or measles) within 4 weeks prior to first study drug administration
-Participants without acceptable evidence of immunity to varicella-zoster virus, mumps, measles, rubella, diphtheria, tetanus and pertussis at Randomization
-Participants with any other significant condition, as assessed by the investigator, which may preclude participant from participating in the study.
-Pregnant or nursing (lactating) female participant
-other protocol-defined inclusion/exclusion criteria may apply


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Nervous System Diseases [C10]

Multiple Sclerosis in pediatric patients
MedDRA version: 20.1 Level: PT Classification code 10028245 Term: Multiple sclerosis System Organ Class: 10029205 - Nervous system disorders

Intervention(s)

Trade Name: Kesimpta
Product Name: ofatumumab
Product Code: OMB157
Pharmaceutical Form: Solution for injection in pre-filled pen
INN or Proposed INN: OFATUMUMAB
CAS Number: 679818-59-8
Current Sponsor code: OMB157
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 50-
Pharmaceutical form of the placebo: Solution for injection in pre-filled pen
Route of administration of the placebo: Subcutaneous use

Trade Name: Mayzent
Product Code: BAF312
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Siponimod
CAS Number: 1234627-85-0
Current Sponsor code: BAF312
Other descriptive name: SIPONIMOD FUMARIC ACID
Concentration unit: mg/g milligram(s)/gram
Concentration type: equal
Concentration number: 2-
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use

Product Name: Siponimod
Product Code: BAF312
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Siponimod
CAS Number: 1234627-85-0
Current Sponsor code: BAF312
Other descriptive name: SIPONIMOD FUMARIC ACID
Concentration unit: mg/g milligram(s)/gram
Concentration type: equal
Concentration number: 1-
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use

Product Name: Siponimod
Product Code: BAF312
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Siponimod
CAS Number: 1234627-85-0
Current Sponsor code: BAF312
Other descriptive name: SIPONIMOD FUMARIC ACID
Concentration unit: mg/g milligram(s)/gram
Concentration type: equal
Concentration number: 0.5-
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use

Trade Name: Mayzent
Product Code: BAF312
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN:

Primary Outcome(s)

Main Objective: To demonstrate the non-inferiority of ofatumumab and/or siponimod as compared to fingolimod as assessed by annualized relapse rate (ARR) in the target pediatric MS participants treated for up to 2-years

Primary end point(s): Annualized relapse rate (ARR of confirmed relapses)

Timepoint(s) of evaluation of this end point: participants treated up to 2-years

Secondary Objective: -Key secondary objective: To demonstrate the superiority of ofatumumab and/ or siponimod as compared to historical interferon ß-1a data, assessed by annualized relapse rate (ARR)
-To evaluate the effects of ofatumumab and/or siponimod versus fingolimod on the number of new or newly enlarging T2 lesions
- To evaluate the effects of ofatumumab and/or siponimod versus fingolimod on neurofilament light chain (NfL) concentrations
- To evaluate the pharmacokinetic (PK) properties of ofatumumab and siponimod (and its metabolite M17) in pediatric MS patients
- To evaluate immunogenicity (ofatumumab)
- To evaluate the safety and tolerability of ofatumumab and siponimod

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: For the key secondary endpoint ARR, the endpoint is for participants treated up to 2-years. Information for the timepoints for other secondary endpoints can be found in the study protocol

Secondary end point(s): -Annualized relapse rate (ARR of confirmed relapses)
-Number of new or newly enlarging T2 lesions on MRI per year (annualized T2 lesion rate)
-Neurofilament light chain (NfL) concentration in serum
-Ofatumumab and siponimod and(metabolite M17) plasma concentrations
-Proportion of participants with antiofatumumab antibodies
-Adverse events, Columbia Suicide Severity Rating Scale (C-SSRS), ECG, laboratory and ophthalmological data, pulmonary function tests and vital signs

Secondary ID(s)

2020-002700-39-DE

CBAF312D2301

Source(s) of Monetary Support

Novartis Pharma AG

Ethics review

Status: Approved
Approval date: 04/08/2021
Contact: