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Safety and Efficacy of Fingolimod in Pediatric Patients With Multiple Sclerosis

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ClinicalTrials.gov Identifier: NCT01892722
Recruitment Status : Recruiting
First Posted : July 4, 2013
Results First Posted : September 19, 2018
Last Update Posted : August 14, 2020
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Tracking Information
First Submitted Date  ICMJE May 8, 2013
First Posted Date  ICMJE July 4, 2013
Results First Submitted Date  ICMJE June 8, 2018
Results First Posted Date  ICMJE September 19, 2018
Last Update Posted Date August 14, 2020
Actual Study Start Date  ICMJE July 26, 2013
Actual Primary Completion Date July 14, 2017   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 8, 2018)
Frequency of Relapses in Patients Treated for up to 24 Months [ Time Frame: 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).
Original Primary Outcome Measures  ICMJE
 (submitted: July 1, 2013)
Frequency of relapses" in patients treated for up to 24 months [ Time Frame: 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).
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: April 12, 2018)
  • New/Newly Enlarged T2 Lesions [ Time Frame: 24 months ]
    Annualized rate of the number of new/newly enlarged T2 lesions up to Month 24
  • Time to First Relapse [ Time Frame: 24 months ]
    Time to first relapse was determined.
  • Proportion of Patients Relapse-free [ Time Frame: 24 months ]
    Proportion of patients relapse-free was determined
  • T1 Gd- Enhancing Lesions [ Time Frame: 24 months ]
    Number of T1 Gd-enhancing lesions per scan up to Month 24
  • Pharmacokinetics (Cavg) of Fingolimod-P [ Time Frame: 24 months ]
    Cavg (average drug concentration over the dose interval) will be evaluated.
  • Pharmacokinetic/Pharmacodynamic Relationship for Fingolimod-P to Lymphocyte Levels [ Time Frame: 24 months ]
    Population PK/PD modeling approaches were used to relate the individual fingolimod-P concentrations to lymphocyte counts.
Original Secondary Outcome Measures  ICMJE
 (submitted: July 1, 2013)
  • Number of new/newly enlarged T2 (n/neT2) lesions [ Time Frame: 24 months ]
    Cumulative number of new/newly enlarged T2 lesions (n/neT2) over 24 months.
  • Frequency and nature of adverse events as a measure of Safety and Tolerability [ Time Frame: 24 months ]
    Based on frequency adverse events (the number and percentage of patients having any AE by primary system organ class and preferred term) and on the incidence of clinically notable laboratory abnormalities.
  • Pharmacokinetics (Cavg)of fingolimod and fingolimod-P [ Time Frame: 24 months ]
    Characterization of pharmacokinetics (PK): Cavg (average drug concentration over the dose interval) will be evaluated. Determine if population covariates affect PK in the pediatric MS population.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Safety and Efficacy of Fingolimod in Pediatric Patients With Multiple Sclerosis
Official Title  ICMJE 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
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 (30 patients) was requested as a post- approval health authority commitment
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
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 30 new younger patients per HA post approval committment.
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Condition  ICMJE Multiple Sclerosis
Intervention  ICMJE
  • Drug: Interferon beta-1a
    Administration once weekly via i.m. injections.
  • 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.

  • Drug: Placebo capsule
    Matching placebo capsule required for double-dummy masking to blind formulations.
  • Drug: Placebo i.m. injection
    Matching placebo i.m. injection required for double-dummy masking to blind formulations.
Study Arms  ICMJE
  • Experimental: 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
    Interventions:
    • Drug: Fingolimod
    • Drug: Placebo capsule
  • Active Comparator: 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
    Interventions:
    • Drug: Interferon beta-1a
    • Drug: Placebo i.m. injection
  • Experimental: 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)
    Intervention: Drug: Fingolimod
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: July 31, 2020)
245
Original Estimated Enrollment  ICMJE
 (submitted: July 1, 2013)
190
Estimated Study Completion Date  ICMJE December 15, 2028
Actual Primary Completion Date July 14, 2017   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 10 Years to 17 Years   (Child)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Novartis Pharmaceuticals 1-888-669-6682 Novartis.email@novartis.com
Contact: Novartis Pharmaceuticals +41613241111
Listed Location Countries  ICMJE 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,   United States
Removed Location Countries Czech Republic,   South Africa
 
Administrative Information
NCT Number  ICMJE NCT01892722
Other Study ID Numbers  ICMJE CFTY720D2311
2011-005677-23 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
Plan Description:

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com

Responsible Party Novartis ( Novartis Pharmaceuticals )
Study Sponsor  ICMJE Novartis Pharmaceuticals
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
PRS Account Novartis
Verification Date July 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP