Safety and Efficacy of Fingolimod in Pediatric Patients With Multiple Sclerosis

NCT ID: NCT01892722

Last Updated: 2025-11-20

Study Results

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Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE3

Total Enrollment

240 participants

Study Classification

INTERVENTIONAL

Study Start Date

2013-07-26

Study Completion Date

2030-02-18

Brief Summary

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

Detailed Description

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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

Conditions

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Multiple Sclerosis

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

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 Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Investigators

Study Groups

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Fingolimod

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

Group Type EXPERIMENTAL

Fingolimod

Intervention Type DRUG

Administrated orally once daily:

0.5 mg capsule for patients over 40 kg or 0.25 mg capsule for patients 40 kg or less.

Placebo capsule

Intervention Type DRUG

Matching placebo capsule required for double-dummy masking to blind formulations.

Interferon beta-1a

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

Group Type ACTIVE_COMPARATOR

Interferon beta-1a

Intervention Type DRUG

Administration once weekly via i.m. injections.

Placebo i.m. injection

Intervention Type DRUG

Matching placebo i.m. injection required for double-dummy masking to blind formulations.

Fingolimod-Younger Cohort

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)

Group Type EXPERIMENTAL

Fingolimod

Intervention Type DRUG

Administrated orally once daily:

0.5 mg capsule for patients over 40 kg or 0.25 mg capsule for patients 40 kg or less.

Interventions

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Interferon beta-1a

Administration once weekly via i.m. injections.

Intervention Type DRUG

Fingolimod

Administrated orally once daily:

0.5 mg capsule for patients over 40 kg or 0.25 mg capsule for patients 40 kg or less.

Intervention Type DRUG

Placebo capsule

Matching placebo capsule required for double-dummy masking to blind formulations.

Intervention Type DRUG

Placebo i.m. injection

Matching placebo i.m. injection required for double-dummy masking to blind formulations.

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* 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



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

* Central review (including initial MRI report) of the diagnosis of pediatric MS will be required for all newly recruited patients.

Exclusion Criteria

* 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


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

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

10 Years

Maximum Eligible Age

17 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Novartis Pharmaceuticals

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Novartis Pharmaceuticals

Role: STUDY_DIRECTOR

Novartis Pharmaceuticals

Locations

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UAB Childrens Hospital Harbor Center Neurology Dept

Birmingham, Alabama, United States

Site Status

Childrens Hospital Los Angeles

Los Angeles, California, United States

Site Status

UCSF

San Francisco, California, United States

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University of Miami

Miami, Florida, United States

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AMO Corporation

Tallahassee, Florida, United States

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Massachusetts General Hospital

Boston, Massachusetts, United States

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Wayne State University

Detroit, Michigan, United States

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Robert Wood Johnson Medical School

New Brunswick, New Jersey, United States

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Childrens Hospital of Philadelphia

Philadelphia, Pennsylvania, United States

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University of Utah Clinical Trials Office

Salt Lake City, Utah, United States

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Novartis Investigative Site

Parkville, Victoria, Australia

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Novartis Investigative Site

Vienna, , Austria

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Novartis Investigative Site

Belo Horizonte, Minas Gerais, Brazil

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Novartis Investigative Site

Rio de Janeiro, Rio de Janeiro, Brazil

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Novartis Investigative Site

São Paulo, São Paulo, Brazil

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Novartis Investigative Site

Goiânia, , Brazil

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Novartis Investigative Site

Sofia, , Bulgaria

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Novartis Investigative Site

Calgary, Alberta, Canada

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Ottawa, Ontario, Canada

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Osijek, , Croatia

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Tallinn, , Estonia

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Bordeaux, , France

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Le Kremlin-Bicêtre, , France

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Marseille, , France

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Montpellier, , France

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Toulouse, , France

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Freiburg im Breisgau, Baden-Wurttemberg, Germany

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Göttingen, Lower Saxony, Germany

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Dresden, Saxony, Germany

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Bochum, , Germany

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Erlangen, , Germany

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Bari, BA, Italy

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Montichiari, BS, Italy

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Catania, CT, Italy

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Milan, MI, Italy

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Cefalù, PA, Italy

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Roma, RM, Italy

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Roma, RM, Italy

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Gallarate, VA, Italy

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Riga, , Latvia

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Kaunas, LTU, Lithuania

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Mexico City, D F, Mexico

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Distrito Federal, , Mexico

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Rotterdam, South Holland, Netherlands

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Lodz, , Poland

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Lublin, , Poland

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Poznan, , Poland

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Wroclaw, , Poland

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San Jorge Childrens Hospital

Santurce, , Puerto Rico

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Novartis Investigative Site

Bucharest, , Romania

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Kazan', , Russia

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Moscow, , Russia

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Moscow, , Russia

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Novosibirsk, , Russia

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Saint Petersburg, , Russia

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Belgrade, , Serbia

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Bratislava, , Slovakia

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Seville, Andalusia, Spain

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Vigo, Pontevedra, Spain

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Barakaldo, Vizcaya, Spain

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Madrid, , Spain

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Málaga, , Spain

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Valencia, , Spain

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Samsun, Atakum, Turkey (Türkiye)

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Izmir, Balcova, Turkey (Türkiye)

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Novartis Investigative Site

Istanbul, Fatih, Turkey (Türkiye)

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Novartis Investigative Site

Ankara, Sihhiye-Altindag, Turkey (Türkiye)

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Novartis Investigative Site

Ankara, Yenimahalle, Turkey (Türkiye)

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Novartis Investigative Site

Kharkiv, , Ukraine

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Novartis Investigative Site

West Midlands, Birmingham, United Kingdom

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Novartis Investigative Site

Edinburgh, , United Kingdom

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Novartis Investigative Site

London, , United Kingdom

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Novartis Investigative Site

London, , United Kingdom

Site Status

Countries

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United States Australia Austria Brazil Bulgaria Canada Croatia Estonia France Germany Italy Latvia Lithuania Mexico Netherlands Poland Puerto Rico Romania Russia Serbia Slovakia Spain Turkey (Türkiye) Ukraine United Kingdom

References

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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.

Reference Type DERIVED
PMID: 31467033 (View on PubMed)

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.

Reference Type DERIVED
PMID: 30207920 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

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Other Identifiers

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2011-005677-23

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CFTY720D2311

Identifier Type: -

Identifier Source: org_study_id

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