Safety and Efficacy of Fingolimod in Pediatric Patients With Multiple Sclerosis

Multiple Sclerosis Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT01892722
• Other study ID #: CFTY720D2311
• Secondary ID: 2011-005677-23
• Status: Recruiting
• Phase: Phase 3
• Start date: July 26, 2013
• Est. completion date: July 12, 2029

Study information

• Verified date: April 2024
• Source: Novartis
• Contact: Novartis Pharmaceuticals
• Phone: 1-888-669-6682
• Email: Novartis.email[@]novartis.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 235
• Est. completion date: July 12, 2029
• Est. primary completion date: July 14, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 10 Years to 17 Years

Eligibility

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.

Related Conditions & MeSH terms

• Multiple Sclerosis
• Sclerosis

Intervention

Drug:
• Interferon beta-1a
Administration once weekly via i.m. injections.
• 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.
• Placebo capsule
Matching placebo capsule required for double-dummy masking to blind formulations.
• Placebo i.m. injection
Matching placebo i.m. injection required for double-dummy masking to blind formulations.

Locations

Country	Name	City	State
Australia	Novartis Investigative Site	Parkville	Victoria
Austria	Novartis Investigative Site	Vienna
Belarus	Novartis Investigative Site	Minsk
Brazil	Novartis Investigative Site	Belo Horizonte	Minas Gerais
Brazil	Novartis Investigative Site	Goiania
Brazil	Novartis Investigative Site	Rio de Janeiro	RJ
Brazil	Novartis Investigative Site	Sao Paulo	SP
Bulgaria	Novartis Investigative Site	Sofia
Canada	Novartis Investigative Site	Calgary	Alberta
Canada	Novartis Investigative Site	Ottawa	Ontario
Croatia	Novartis Investigative Site	Osijek
Estonia	Novartis Investigative Site	Tallinn
France	Novartis Investigative Site	Bordeaux Cedex
France	Novartis Investigative Site	Le Kremlin Bicetre
France	Novartis Investigative Site	Marseille Cedex 05
France	Novartis Investigative Site	Montpellier
France	Novartis Investigative Site	Toulouse Cedex
Germany	Novartis Investigative Site	Bochum
Germany	Novartis Investigative Site	Bonn
Germany	Novartis Investigative Site	Dresden
Germany	Novartis Investigative Site	Erlangen
Germany	Novartis Investigative Site	Essen
Germany	Novartis Investigative Site	Freiburg
Germany	Novartis Investigative Site	Gottingen
Germany	Novartis Investigative Site	Hamburg
Germany	Novartis Investigative Site	Muenchen
Germany	Novartis Investigative Site	Muenster
Italy	Novartis Investigative Site	Bari	BA
Italy	Novartis Investigative Site	Catania	CT
Italy	Novartis Investigative Site	Cefalu	PA
Italy	Novartis Investigative Site	Gallarate	VA
Italy	Novartis Investigative Site	Milano	MI
Italy	Novartis Investigative Site	Montichiari	BS
Italy	Novartis Investigative Site	Napoli
Italy	Novartis Investigative Site	Roma	RM
Italy	Novartis Investigative Site	Roma	RM
Latvia	Novartis Investigative Site	Riga
Lithuania	Novartis Investigative Site	Kaunas	LTU
Mexico	Novartis Investigative Site	Ciudad De Mexico	D F
Mexico	Novartis Investigative Site	Merida	Yucatán
Mexico	Novartis Investigative Site	Mexico	Distrito Federal
Mexico	Novartis Investigative Site	Mexico	Distrito Federal
Mexico	Novartis Investigative Site	Mexico	Distrito Federal
Netherlands	Novartis Investigative Site	Rotterdam
Poland	Novartis Investigative Site	Lodz
Poland	Novartis Investigative Site	Lublin
Poland	Novartis Investigative Site	Poznan
Poland	Novartis Investigative Site	Wroclaw
Puerto Rico	Novartis Investigative Site	Santurce
Romania	Novartis Investigative Site	Bucuresti
Russian Federation	Novartis Investigative Site	Kazan
Russian Federation	Novartis Investigative Site	Moscow
Russian Federation	Novartis Investigative Site	Moscow
Russian Federation	Novartis Investigative Site	Novosibirsk
Russian Federation	Novartis Investigative Site	St. Petersburg
Serbia	Novartis Investigative Site	Belgrade
Serbia	Novartis Investigative Site	Kragujevac
Serbia	Novartis Investigative Site	Novi Sad
Slovakia	Novartis Investigative Site	Bratislava	Slovensko
Spain	Novartis Investigative Site	Barakaldo	Pais Vasco
Spain	Novartis Investigative Site	Barcelona	Catalunya
Spain	Novartis Investigative Site	Esplugues De Llobregat	Barcelona
Spain	Novartis Investigative Site	Madrid
Spain	Novartis Investigative Site	Madrid
Spain	Novartis Investigative Site	Malaga	Andalucia
Spain	Novartis Investigative Site	Sevilla	Andalucia
Spain	Novartis Investigative Site	Valencia	Comunidad Valenciana
Spain	Novartis Investigative Site	Vigo	Pontevedra
Sweden	Novartis Investigative Site	Lund
Turkey	Novartis Investigative Site	Ankara
Turkey	Novartis Investigative Site	Ankara
Turkey	Novartis Investigative Site	Istanbul	TUR
Turkey	Novartis Investigative Site	Izmir
Turkey	Novartis Investigative Site	Konak-Izmir
Turkey	Novartis Investigative Site	Samsun
Ukraine	Novartis Investigative Site	Cherkasy
Ukraine	Novartis Investigative Site	Dnipropetrovsk
Ukraine	Novartis Investigative Site	Kharkiv
Ukraine	Novartis Investigative Site	Kharkiv
Ukraine	Novartis Investigative Site	Kiev
Ukraine	Novartis Investigative Site	Lviv
Ukraine	Novartis Investigative Site	Odesa
Ukraine	Novartis Investigative Site	Vinnytsa
United Kingdom	Novartis Investigative Site	Edinburgh
United Kingdom	Novartis Investigative Site	London
United Kingdom	Novartis Investigative Site	London
United Kingdom	Novartis Investigative Site	West Midlands	Birmingham
United States	Novartis Investigative Site	Aurora	Colorado
United States	Novartis Investigative Site	Birmingham	Alabama
United States	Novartis Investigative Site	Boston	Massachusetts
United States	Novartis Investigative Site	Boston	Massachusetts
United States	Novartis Investigative Site	Chapel Hill	North Carolina
United States	Novartis Investigative Site	Chicago	Illinois
United States	Novartis Investigative Site	Detroit	Michigan
United States	Novartis Investigative Site	Durham	North Carolina
United States	Novartis Investigative Site	Greenville	South Carolina
United States	Novartis Investigative Site	Little Rock	Arkansas
United States	Novartis Investigative Site	Los Angeles	California
United States	Novartis Investigative Site	Miami	Florida
United States	Novartis Investigative Site	New Brunswick	New Jersey
United States	Novartis Investigative Site	Orlando	Florida
United States	Novartis Investigative Site	Philadelphia	Pennsylvania
United States	Novartis Investigative Site	Rochester	New York
United States	Novartis Investigative Site	Salt Lake City	Utah
United States	Novartis Investigative Site	San Antonio	Texas
United States	Novartis Investigative Site	San Francisco	California
United States	Novartis Investigative Site	Stony Brook	New York
United States	Novartis Investigative Site	Tallahassee	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

United States,  Australia,  Austria,  Belarus,  Brazil,  Bulgaria,  Canada,  Croatia,  Estonia,  France,  Germany,  Italy,  Latvia,  Lithuania,  Mexico,  Netherlands,  Poland,  Puerto Rico,  Romania,  Russian Federation,  Serbia,  Slovakia,  Spain,  Sweden,  Turkey,  Ukraine,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Frequency of Relapses in Patients Treated for up to 24 Months	Frequency of relapses assessed by the annualized relapse rate (ARR). The ARR is defined as the average number of confirmed relapses per year (total number of confirmed relapses divided by the total days in the study multiplied by 365.25).	24 months
Secondary	New/Newly Enlarged T2 Lesions	Annualized rate of the number of new/newly enlarged T2 lesions up to Month 24	24 months
Secondary	Time to First Relapse	Time to first relapse was determined.	24 months
Secondary	Proportion of Patients Relapse-free	Proportion of patients relapse-free was determined	24 months
Secondary	T1 Gd- Enhancing Lesions	Number of T1 Gd-enhancing lesions per scan up to Month 24	24 months
Secondary	Pharmacokinetics (Cavg) of Fingolimod-P	Cavg (average drug concentration over the dose interval) will be evaluated.	24 months
Secondary	Pharmacokinetic/Pharmacodynamic Relationship for Fingolimod-P to Lymphocyte Levels	Population PK/PD modeling approaches were used to relate the individual fingolimod-P concentrations to lymphocyte counts.	24 months

External Links

•   Recruitment website