Safety and Efficacy of Fingolimod in Pediatric Patients With Multiple Sclerosis

Novartis

Status and phase: Enrolling; Phase 3

Conditions: Multiple Sclerosis

Treatments: Drug: Interferon beta-1a; Drug: Placebo capsule; Drug: Fingolimod; Drug: Placebo i.m. injection

Study type: Interventional

Funder types: Industry

Identifiers

NCT01892722

CFTY720D2311

2011-005677-23 (EudraCT Number)

Details and patient eligibility

About

To evaluate the safety and efficacy of fingolimod vs. interferon beta-1a i.m. in pediatric patients with multiple sclerosis (MS)

Full description

The study is divided into a Core Phase, which includes the Double-Blind Treatment Period, and an Extension Phase in which all patients will be treated with fingolimod. The Core Phase is a 24-month, double-blind, randomized, active-controlled, parallel-group multicenter study phase to evaluate the efficacy and safety of fingolimod compared to IFN β-1a in children/adolescent patients aged 10-17 years old with MS. The Extension Phase is a 60-month (5 year) study phase for patients who complete the Core Phase of the study and meet all inclusion/exclusion criteria and for patients who will be recruited in the younger cohort to participate in the Extension Phase. The 'younger cohort' refers to the population of pediatric patients fulfilling any single one or a combination of the following criteria: being ≤12 years of age, or weighing ≤40 kg, or being prepubertal (i.e. pubertal status of Tanner stage <2). The recruitment of the younger cohort (up to 25 patients) was requested as a post- approval health authority commitment

Enrollment: 245 estimated patients

Sex: All

Ages: 10 to 17 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Key Inclusion Criteria Core Phase:

• diagnosis of multiple sclerosis
• at least one MS relapse during the previous year or two MS relapses in the previous 2 years or evidence of Gd enhancing lesions on MRI within 6 months EDSS score of 0 to 5.5, inclusive

Key Exclusion Criteria Core Phase:

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

Key Inclusion Criteria Extension Phase:

Applies to all patients participating in the Core Phase and then entering the Extension Phase. 1. Patients that originally met Core Phase Inclusion criteria and completed the Core phase on or off of study drug.

Applies to patients newly recruited to participate in the Extension Phase.

• All newly recruited patients' that enroll directly into the Extension Phase must fulfill the local country health authority product label approved for pediatric age group for inclusion criteria.
• Central review (including initial MRI report) of the diagnosis of pediatric MS will be required for all newly recruited patients.

Key Exclusion Criteria Extension Phase:

Applies to patients who completed the Core Phase, but prematurely discontinued study drug.

1. Premature discontinuation of the study drug during the Core Phase due to:

   • an adverse event,
   • serious adverse event,
   • laboratory abnormality
   • other conditions leading to permanent study drug discontinuation due to safety reasons

2. Patients with known new events or concomitant medications (washout periods required prior to Visit 15) that would exclude them from the Core Phase exclusion criteria. Serological or other additional tests will not be required.

Applies to patients newly recruited in the younger cohort to participate in the Extension Phase.

1. All newly recruited patients in the younger cohort that enroll directly into the Extension Phase must fulfill the exclusion criteria for the core phase.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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245 participants in 3 patient groups

Fingolimod

Experimental group

Description:

Fingolimod was administered orally once daily at a dose of either 0.5 mg or 0.25 mg (depending on patient's body weight) with the aim to achieve systemic exposure in range of that in adults at the licensed 0.5 mg dose. Participants in this arm during core continued into extension and received open-label treatment

Treatment:

Drug: Fingolimod

Drug: Placebo capsule

Interferon beta-1a

Active Comparator group

Description:

An intramuscular (IM) injection of Interferon beta-1a was administered once weekly during core phase. Participants switched to receive open-label fingolimod in extension phase

Treatment:

Drug: Placebo i.m. injection

Drug: Interferon beta-1a

Fingolimod-Younger Cohort

Experimental group

Description:

The 'younger cohort' refers to the new pediatric patients to be recruited in the extension phase who fulfill any single one or a combination of the following criteria: being ≤12 years of age, or weighing ≤40 kg, or being prepubertal (i.e. pubertal status of Tanner stage \<2)

Treatment:

Drug: Fingolimod