Study of Efficacy and Safety of Fingolimod (Gilenya) 0.5 mg in Chinese Patients With Relapsing Multiple Sclerosis (RMS) Patients

Phase 4

Completed

Conditions: Relapsing Multiple Sclerosis (RMS)

Interventions: Drug: Fingolimod 0.5mg

Registration Number: NCT04667949

Lead Sponsor: Novartis Pharmaceuticals

Brief Summary: The main purpose of this study was to assess the efficacy and safety of 0.5mg Fingolimod (Gilenya) in Chinese patients with relapsing multiple sclerosis (RMS)

Detailed Description: This was a 24-month, open-label, multicenter, interventional, single-arm study to collect efficacy and, safety of oral fingolimod 0.5 mg/day in approximately 100 relapsing multiple sclerosis (RMS) participants in China.

The study consisted of three Phases:

* Screening (up to 1 month): After signing informed consent, participants entered a Screening Phase to determine eligibility according to inclusion and exclusion criteria.

* Treatment Period (24 months): On visit Day 1, all eligibility criteria were confirmed, including a pre-dose ECG and vital signs. The first dose of study drug was taken in the clinic on Day 1 and the participant was monitored for 6 hours after the first dose administration before discharge. Participants returned to site for evaluation at month 1 and then every three months until the end of treatment up to 24 months.

* Follow Up (2 months): Subjects who completed Treatment Period or discontinued from treatment returned for the Follow-up visit 2 months after the last dose of study drug.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 98

Inclusion Criteria

Participant 10 to 17 years old inclusive with weight > 40kg.
Participant 18 to 65 years old inclusive;
Participants with relapsing multiple sclerosis
Participants never used fingolimod before enrollment
Subjects with Expanded Disability Status Scale (EDSS) score of 0 - 6.0 (inclusive) at Screening

Exclusion Criteria

Participants with certain cardiovascular conditions and/or findings in the screening ECG.
Diagnosis of macular edema during screening visit.
Increased risk for opportunistic infections
Participants with known active malignancies.
Participants who have been treated with teriflunomide within 3.5 months prior to baseline, except if active washout.
Participants with severe active infections, active chronic infection.
Participants with severe liver impairment.
Pregnant confirmed by a positive pregnancy test or nursing (lactating) women.

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Fingolimod	Fingolimod 0.5mg	Fingolimod 0.5 mg capsule taken orally once daily

Primary Outcome Measures

Name	Time	Method
Adjusted Annualized Relapse Rate (ARR) in Adult Group	Baseline to Month 24	A confirmed relapse is any relapse that is accompanied by an increase of at least 0.5 on the EDSS or an increase of 1 point on two different Functional Systems (FS) of the EDSS or 2 points on one of the FS (excluding Bowel/Bladder or Cerebral FS) as confirmed by the treating physician. The adjusted annualized relapse rate (ARR) was estimated by a negative binomial regression model with log-link function, the cumulative number of confirmed MS relapses per subject as the response variable, number of relapses in the previous two years before enrollment and baseline EDSS as continuous covariates. Natural log of time on study in years was used as the offset variable to account for the varying lengths of subjects' time in the study. The adjusted ARR (i.e.model-based estimate adjusted for covariates) and the corresponding 95% confidence interval were obtained. As per SAP this analysis was only performed for the Adult group. Descriptive data is presented in subsequent OMs.

Secondary Outcome Measures

Name	Time	Method
Number of Participants With Treatment Emergent Adverse Events (AE) and Serious Adverse Events (SAE)	From first dose of study treatment to 45 days after last study dose up to aproximately 25.5 months	An adverse event (AE) is any untoward medical occurrence in a clinical investigation subject after providing written informed consent for participation in the study. For reporting purposes, the main focus was on treatment emergent adverse event (TEAE), defined as any AE which started on or after the day of first dose of study medication or events present prior to the start of treatment but increased in severity.
Annualized Rate of the Number of New or Newly Enlarged T2 Lesions	Baseline to end of treatment (up to Month 24)	Obtained from fitting a negative binomial regression model with log-link function, the total number of new or newly enlarged T2 lesions during the treatment period (per participant) as the response variable. The model included baseline age and volume of T2 lesions at baseline as continuous covariates. Natural log of time from screening scan in years was used as the offset. Baseline is defined as the last non-missing assessment obtained prior to the first administration of study drug. As per SAP this analysis was only performed for the Adult group.
Change From Baseline in Number of New or Newly Enlarged T2 Lesions	Baseline up to Month 24	Number of new/newly enlarged T2 lesions since baseline as measured by MRI
Change From Baseline in T2 Lesion Volume	Baseline up to Month 24	T2 lesion volume as measured by MRI and calculated as post-baseline value - baseline value
Number of Gd-enhancing T1 Lesions Per Scan in Adult Group	Baseline up to Month 24	Obtained from fitting a negative binomial regression model with log-link function, the total number of Gd-enhancing T1 lesions during the treatment period (per patient) as the response variable. The model included baseline age and number of Gd-enhancing T1 lesions at baseline as continuous covariates. Natural log of the number of MRI scans was used as the offset. MRI scans were performed at baseline, month 12 and month 24 and End of treatment for participants that discontinued treatment. Unscheduled MRIs could be performed at the investigator's judgement. As per SAP this analysis was only performed for the Adult group.
Number of Gd-enhancing T1 Lesions	Baseline up to Month 24	Number of Gd-enhancing T1 lesions as measured by MRI
Change From Baseline in Gd-enhancing T1 Lesion Volume	Baseline up to Month 24	Gd-enhancing T1 lesion volume as measured by MRI and calculated as post-baseline value - baseline value
Number of T1 Hypo-intense Lesions	Baseline up to Month 24	Number of T1 hypo-intense lesions as measured by MRI
Change From Baseline in T1 Hypo-intense Lesion Volume	Baseline up to Month 24	T1 hypo-intense lesions as measured by MRI and calculated as post-baseline value - baseline value