Clinical Trials

Inclusion Criteria - Core Part:

• 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 (Thompson et al 2018).
• 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.

Inclusion Criteria - Extension Part:

• Re-consent / assent must be obtained prior to E-Day 1 in the Extension part.
• Participants who complete the Core Part on randomized double-blind treatment.

Exclusion Criteria - Core Part:

• Participants with progressive MS.
• Participants meeting the definition of ADEM (Krupp et al 2013); participants meeting criteria for neuromyelitis optica (Wingerchuk et al 2006) 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 immune deficiency, drug-induced immune deficiency) or tested positive for HIV at Screening.
• Participants with neurological symptoms consistent with 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, such as:
  • History of symptomatic bradycardia or recurrent syncope;
  • Known ischaemic heart disease;
  • History of congenital heart disease (except conditions such as small patent ductus arteriosus, atrial septal defect, ventricular septal defect, or an ECG or rhythm abnormality, which have been assessed by a pediatric cardiologist and considered to be clinically insignificant);
  • Cerebrovascular disease;
  • History of myocardial infarction;
  • Congestive heart failure;
  • History of cardiac arrest;
  • Resting (sitting) heart rate < 55 bpm (in participants 12 years or older) and <60 bpm (in participants below 12 years);
  • Severe untreated sleep apnea;
  • Sick sinus syndrome or sino-atrial heart block;
  • Clinically significant cardiac arrhythmias (e.g., ventricular tachycardia), complete left bundle branch block, high-grade AV block (e.g., bifascicular block, Mobitz type II and third degree AV block) ;
  • QTcF interval > 450 msec in males and > 460 msec in females or relevant risk factors for QT prolongation (e.g., hypokalaemia, hypomagnesemia, congenital QT prolongation) or treatment with QT prolonging drugs with a known risk of Torsades de pointes or history of familial long QT syndrome or known family history of Torsades de Pointes;
  • Uncontrolled arterial hypertension despite prescribed medications.
• Participants with any pulmonary conditions, as determined by the investigator, including severe asthma defined as per the 2010 World Health Organization (WHO) uniform definition on severe asthma (Bousquet et al 2010);
• Participants with any of the following neurologic/psychiatric disorder:
  • History of any type of epileptic seizure(s) as well as psychogenic non-epileptic seizure(s) during the past 12 months before screening;
  • Ongoing substance abuse (drug or alcohol) or any other factor (i.e., serious psychiatric condition) that may interfere with the participant’s ability to cooperate and comply with the study procedures;
  • History of clinically significant CNS disease (e.g., stroke, traumatic brain or spinal injury, history or presence of myelopathy) or neurological disorders which may mimic MS.
• Participants with a score of “yes” on item 4 or item 5 of the Suicidal Ideation section of the C‑SSRS, if this ideation occurred in the past 6 months, or with a score of “yes” on any item of the Suicidal Behavior section, except for “Non-Suicidal Self Injurious Behavior”, if this behavior occurred in the past 2 years.
• Any history of malignancy of any organ system
• Any of the following conditions or treatments that may impact the safety of the participant:
  • Participants with any history of or active severe respiratory disease as determined by the investigator;
  • Severe hepatic impairment (Child-Pugh class C) or any chronic liver or biliary disease, acute or chronic pancreatitis, with the exception of Gilbert’s syndrome;
  • Participants with severe renal insufficiency (GFR <30 mL/min/1.73 m^2).
• Any of the following abnormal laboratory values as confirmed by the central laboratory prior to first study drug administration:
  • Positive results of screening period testing for serological markers for hepatitis A, B, C and E indicating acute or chronic infection;
  • Anti-HAV IgM positive;
  • If HBs Ag and/or anti-HBc positive, HBV-DNA Polymerase Chain Reaction (PCR) will be performed (if negative, participant can be included);
  • If anti-HCV antibody positive, HCV-RNA PCR will be performed (if negative, participant can be included);
  • If anti- HEV IgM or IgG positive, HEV-RNA PCR will be performed (if negative, participant can be included).