Clinical trial NCT01892722: Safety and Efficacy of Fingolimod in Pediatric Patients With Multiple Sclerosis
Official title: A 2 Year, Double-blind, Randomized, Multicenter, Active-controlled Core Phase to Evaluate Safety & Efficacy of Daily Fingolimod vs Weekly Interferon β-1a im in Pediatric Patients With Multiple Sclerosis and 5 Year Fingolimod Extension Phase
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Multiple Sclerosis
Keywords: pediatric
multiple sclerosis
fingolimod
pre-pubertal
low weight
children
adolescent
MS
core phase
extension phase
younger cohort
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2013-07-04
Enrollment: 240
Sex: ALL
Minimum age (years): 10
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: There are 2 arms in the core phase. In the extension phase all participants are receiving open-label.study drug. A third arm has been added to enroll up to 25 new younger patients per HA post approval commitment.
Primary purpose: TREATMENT

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

Detailed 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

Eligibility 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.

Primary outcomes:
measure: Frequency of Relapses in Patients Treated for up to 24 Months
timeFrame: 24 months
Secondary outcomes:
measure: New/Newly Enlarged T2 Lesions
timeFrame: 24 months
measure: Time to First Relapse
timeFrame: 24 months
measure: Proportion of Patients Relapse-free
timeFrame: 24 months
measure: T1 Gd- Enhancing Lesions
timeFrame: 24 months
measure: Pharmacokinetics (Cavg) of Fingolimod-P
timeFrame: 24 months
measure: Pharmacokinetic/Pharmacodynamic Relationship for Fingolimod-P to Lymphocyte Levels
timeFrame: 24 months
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: UAB Childrens Hospital Harbor Center Neurology Dept
state: Alabama
city: Los Angeles
country: United States
facility: Childrens Hospital Los Angeles
state: California
city: San Francisco
country: United States
facility: UCSF
state: California
city: Miami
country: United States
facility: University of Miami
state: Florida
city: Tallahassee
country: United States
facility: AMO Corporation
state: Florida
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Detroit
country: United States
facility: Wayne State University
state: Michigan
city: New Brunswick
country: United States
facility: Robert Wood Johnson Medical School
state: New Jersey
city: Philadelphia
country: United States
facility: Childrens Hospital of Philadelphia
state: Pennsylvania
city: Salt Lake City
country: United States
facility: University of Utah Clinical Trials Office
state: Utah
city: Parkville
country: Australia
facility: Novartis Investigative Site
state: Victoria
city: Wien
country: Austria
facility: Novartis Investigative Site
city: Belo Horizonte
country: Brazil
facility: Novartis Investigative Site
state: Minas Gerais
city: Rio de Janeiro
country: Brazil
facility: Novartis Investigative Site
state: RJ
city: Sao Paulo
country: Brazil
facility: Novartis Investigative Site
state: SP
city: Goiania
country: Brazil
facility: Novartis Investigative Site
city: Sofia
country: Bulgaria
facility: Novartis Investigative Site
city: Calgary
country: Canada
facility: Novartis Investigative Site
state: Alberta
city: Ottawa
country: Canada
facility: Novartis Investigative Site
state: Ontario
city: Osijek
country: Croatia
facility: Novartis Investigative Site
city: Tallinn
country: Estonia
facility: Novartis Investigative Site
city: Bordeaux Cedex
country: France
facility: Novartis Investigative Site
city: Le Kremlin Bicetre
country: France
facility: Novartis Investigative Site
city: Marseille
country: France
facility: Novartis Investigative Site
city: Montpellier
country: France
facility: Novartis Investigative Site
city: Toulouse Cedex
country: France
facility: Novartis Investigative Site
city: Goettingen
country: Germany
facility: Novartis Investigative Site
state: Niedersachsen
city: Bochum
country: Germany
facility: Novartis Investigative Site
city: Dresden
country: Germany
facility: Novartis Investigative Site
city: Erlangen
country: Germany
facility: Novartis Investigative Site
city: Freiburg
country: Germany
facility: Novartis Investigative Site
city: Bari
country: Italy
facility: Novartis Investigative Site
state: BA
city: Montichiari
country: Italy
facility: Novartis Investigative Site
state: BS
city: Catania
country: Italy
facility: Novartis Investigative Site
state: CT
city: Milano
country: Italy
facility: Novartis Investigative Site
state: MI
city: Cefalu
country: Italy
facility: Novartis Investigative Site
state: PA
city: Roma
country: Italy
facility: Novartis Investigative Site
state: RM
city: Roma
country: Italy
facility: Novartis Investigative Site
state: RM
city: Gallarate
country: Italy
facility: Novartis Investigative Site
state: VA
city: Riga
country: Latvia
facility: Novartis Investigative Site
city: Kaunas
country: Lithuania
facility: Novartis Investigative Site
state: LTU
city: Ciudad De Mexico
country: Mexico
facility: Novartis Investigative Site
state: D F
city: Distrito Federal
country: Mexico
facility: Novartis Investigative Site
city: Rotterdam
country: Netherlands
facility: Novartis Investigative Site
city: Lodz
country: Poland
facility: Novartis Investigative Site
city: Lublin
country: Poland
facility: Novartis Investigative Site
city: Poznan
country: Poland
facility: Novartis Investigative Site
city: Wroclaw
country: Poland
facility: Novartis Investigative Site
city: Santurce
country: Puerto Rico
facility: San Jorge Childrens Hospital
city: Bucuresti
country: Romania
facility: Novartis Investigative Site
city: Kazan
country: Russian Federation
facility: Novartis Investigative Site
city: Moscow
country: Russian Federation
facility: Novartis Investigative Site
city: Moscow
country: Russian Federation
facility: Novartis Investigative Site
city: Novosibirsk
country: Russian Federation
facility: Novartis Investigative Site
city: St Petersburg
country: Russian Federation
facility: Novartis Investigative Site
city: Belgrade
country: Serbia
facility: Novartis Investigative Site
city: Bratislava
country: Slovakia
facility: Novartis Investigative Site
city: Malaga
country: Spain
facility: Novartis Investigative Site
state: Andalucia
city: Sevilla
country: Spain
facility: Novartis Investigative Site
state: Andalucia
city: Valencia
country: Spain
facility: Novartis Investigative Site
state: Comunidad Valenciana
city: Vigo
country: Spain
facility: Novartis Investigative Site
state: Pontevedra
city: Baracaldo
country: Spain
facility: Novartis Investigative Site
state: Vizcaya
city: Madrid
country: Spain
facility: Novartis Investigative Site
city: Istanbul
country: Turkey
facility: Novartis Investigative Site
state: TUR
city: Ankara
country: Turkey
facility: Novartis Investigative Site
city: Ankara
country: Turkey
facility: Novartis Investigative Site
city: Izmir
country: Turkey
facility: Novartis Investigative Site
city: Samsun
country: Turkey
facility: Novartis Investigative Site
city: Kharkiv
country: Ukraine
facility: Novartis Investigative Site
city: West Midlands
country: United Kingdom
facility: Novartis Investigative Site
state: Birmingham
city: Edinburgh
country: United Kingdom
facility: Novartis Investigative Site
city: London
country: United Kingdom
facility: Novartis Investigative Site
city: London
country: United Kingdom
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References:
citation: Deiva K, Huppke P, Banwell B, Chitnis T, Gartner J, Krupp L, Waubant E, Stites T, Pearce GL, Merschhemke M. Consistent control of disease activity with fingolimod versus IFN beta-1a in paediatric-onset multiple sclerosis: further insights from PARADIGMS. J Neurol Neurosurg Psychiatry. 2020 Jan;91(1):58-66. doi: 10.1136/jnnp-2019-321124. Epub 2019 Aug 29.
citation: Chitnis T, Arnold DL, Banwell B, Bruck W, Ghezzi A, Giovannoni G, Greenberg B, Krupp L, Rostasy K, Tardieu M, Waubant E, Wolinsky JS, Bar-Or A, Stites T, Chen Y, Putzki N, Merschhemke M, Gartner J; PARADIGMS Study Group. Trial of Fingolimod versus Interferon Beta-1a in Pediatric Multiple Sclerosis. N Engl J Med. 2018 Sep 13;379(11):1017-1027. doi: 10.1056/NEJMoa1800149.