Phase 2 Extension Trial in Patients With Relapsing-Remitting Multiple Sclerosis (RRMS)

Study Overview
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Brief Summary
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The objective of this active-drug Extension Study is to evaluate the continuing safety and efficacy of ONO-4641 (MSC2430913A) in subjects with relapsing-remitting multiple sclerosis (RRMS) who have completed an initial 26-week Core Study (ONO-4641POU006 [NCT01081782]).

Official Title
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A Safety and Efficacy Extension Study of ONO-4641 (MSC2430913A) in Patients With Relapsing-Remitting Multiple Sclerosis

Conditions
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Multiple Sclerosis

Intervention / Treatment
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* Drug: ONO-4641
* Drug: ONO-4641
* Drug: ONO-4641
* Drug: ONO-4641
* Drug: ONO-4641
* Drug: ONO-4641


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Completed 26 weeks of double-blind phase of Study ONO-4641POU006 Exclusion Criteria: Presence of any dermatological abnormalities during Study ONO-4641POU006 that could increase the risk of the patient developing a skin cancer

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ONO-4641 0.15 milligram (mg) - 0.15 mg<br> | Drug: ONO-4641<br>* Subjects will be administered with ONO-4641 at a dose of 0.15 milligram (mg) in the core study will be administered with ONO-4641 0.15 mg in this extension study for a duration of 225 weeks.<br>* Other names: Ceralifimod;|
| Experimental: ONO-4641 0.10 mg - 0.10 mg<br> | Drug: ONO-4641<br>* Subjects will be administered with ONO-4641 at a dose of 0.10 mg in the core study will be administered with ONO-4641 0.10 mg in this extension study for a duration of 225 weeks.<br>* Other names: Ceralifimod;|
| Experimental: ONO-4641 0.05 mg - 0.05 mg<br> | Drug: ONO-4641<br>* Subjects will be administered with ONO-4641 at a dose of 0.05 mg in the core study will be administered with ONO-4641 0.05 mg in this extension study for a duration of 225 weeks.<br>* Other names: Ceralifimod;|
| Experimental: Placebo - ONO4641 0.15 mg<br> | Drug: ONO-4641<br>* Subjects will receive placebo in the core study will be administered with ONO-4641 0.15 mg in this extension study for a duration of 225 weeks.<br>* Other names: Ceralifimod;|
| Experimental: Placebo - ONO4641 0.10 mg<br> | Drug: ONO-4641<br>* Subjects will receive placebo in the core study will be administered with ONO-4641 0.10 mg in this extension study for a duration of 225 weeks.<br>* Other names: Ceralifimod;|
| Experimental: Placebo - ONO4641 0.05 mg<br> | Drug: ONO-4641<br>* Subjects will receive placebo in the core study will be administered with ONO-4641 0.05 mg in this extension study for a duration of 225 weeks.<br>* Other names: Ceralifimod;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects With Clinically Significant Abnormal Vital Signs | Vital signs included oral temperature, pulse, respiration rate and blood pressure (BP) (taken after 5 minutes in the sitting position). The abnormalities in vital signs were decided as clinically significant or not based on the clinical judgment of the investigator. | Baseline up to Week 255 | 
| Change From Baseline in Forced Expiratory Volume in One Second (FEV1) (Percent (%) Predicted Value) | FEV1 was defined as the maximal volume of air exhaled in the 1st second of a forced expiration from a position of full inspiration. FEV1 was obtained from spirometry, performed before study treatment administration. Early termination visit was recorded when the subject was early terminated from the study during the first 2.5 year period, while early termination 2 visit was recorded when the subject early terminated from the study during the additional 2 year period with delay shall be defined. | Baseline, Week 40, 52, 76, 100, 124, 148, early termination, Week 152, 200, early termination 2, Week 255 | 
| Change From Baseline in Forced Vital Capacity (FVC) | FVC (% of predicted value) was the volume of air which was forcibly exhaled from the lungs after taking the deepest breath possible. Early termination visit was recorded when the subject was early terminated from the study during the first 2.5 year period, while early termination 2 visit was recorded when the subject early terminated from the study during the additional 2 year period with delay shall be defined. | Baseline, Week 40, 52, 76, 100, 124, 148, early termination, Week 152, 200, early termination 2, Week 255 | 
| Change From Baseline in Diffusing Capacity of Lung for Carbon Monoxide (DLCO) | DLCO was one of the most clinically valuable tests of lung function. The DLCO measure the ability of the lungs to transfer gas from inhaled air to the red blood cells in pulmonary capillaries. Early termination visit was recorded when the subject was early terminated from the study during the first 2.5 year period, while early termination 2 visit was recorded when the subject was early terminated from the study during the additional 2 year period with delay. The values for the DLCO % of predicted was defined as the mean value of 2 test results that were within a 10% variability of each other. | Baseline, Week 40, 52, early termination, Week 152, 200, 255 | 
| Number of Subjects With Clinically Significant Abnormal Electrocardiogram (ECG) Measures | The 12-lead ECG was recorded after the subject was in supine position for 5 minutes. ECGs were acquired on digital cardiographs. Abnormal findings were analyzed as clinically significant or not clinically significant as per the discretion of the study investigator. | Baseline up to Week 255 | 
| Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination | Subjects underwent comprehensive ophthalmic examination (COE) including best corrected visual acuity (Snellen), manifest refractions, pupil examination, ocular motility, nystagmus, confrontation visual fields, Ishihara color plates, Amsler grid, and tonometry as well as a biomicroscopy slit lamp examination of the conjunctiva, cornea, anterior chamber, iris and lens; and a fundoscopic examination (with dilation) of the vitreous, optic nerve, retinal vessels, macula, and peripheral retina. Optical Coherence Tomography (OCT): Thicknesses of the macular retina and retinal nerve fiber layer at the optic nerve head in each eye was assessed by OCT using the fast macular thickness map scan and the fast retinal nerve fiber layer (RNFL) scan features, respectively. The abnormalities of the ophthalmologic examination was judged to be clinically significant or not as per the investigators discretion. The ophthalmologic examination was performed for both right eye (RE) and left eye (LE). | Baseline up to Week 255 | 
| Number of Subjects With Clinically Significant Abnormalities in Dermatological Examination | A whole body examination, paying particular attention to identify precancerous or cancerous lesions was done by a dermatologist and based on the clinical judgment of the dermatologist the abnormalities were categorized as clinically significant or clinically not significant. Early termination visit was recorded when the subject was early terminated from the study during the first 2.5 year period, while early termination 2 visit was recorded when the subject early terminated from the study during the additional 2 year period with delay shall be defined. | Baseline up to end of the treatment, assessed up to Week 255 | 
| Number of Subjects With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, TEAEs Leading to Death and TEAEs Leading to Discontinuation | An Adverse Event (AE) was defined as any new untoward medical occurrences/worsening of pre-existing medical condition without regard to possibility of causal relationship. A Serious Adverse Event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect. TEAEs were defined as the AEs that occur between first dose of study drug administration and 35 days after the last dose of study drug administration that were absent before treatment or that worsened relative to pretreatment state. | From the first dose of study drug administration up to 35 days after the last dose of study drug administration, assessed up to 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Gadolinium (Gd)-Enhanced Lesions | Gd-enhanced lesions were obtained by magnetic resonance imaging (MRI) at each scheduled assessment visit over the study period. Extension study baseline is defined as the measurement most immediately prior to or on the day of the first dose day of extension study. End of treatment (EoT) lesion count is the average number of lesion counts per scan, calculated by dividing the sum of all lesion counts by number of scans during the extension treatment period. Early termination visit was recorded when the subject was early terminated from the study during the first 2.5 year period, while early termination 2 visit was recorded when the subject early terminated from the study during the additional 2 year period with delay. Extension study baseline is defined as the measurement most immediately prior to or on the day of the first dose day of extension study.Full Analysis Set (FAS) included all subjects who provided any post baseline efficacy data. | Baseline, Week 40, 52, 100, 148, early termination, Week 152, 200, early termination 2, Week 255 and end of treatment (5 years) | 
| Change From Baseline in Lesion Volume at the End of the Treatment (EoT) | Brain lesion volume was obtained by magnetic resonance imaging (MRI). Extension study baseline was defined as the measurement most immediately prior to or on the day of the first dose day of extension study. End of treatment (EOT) was defined as the last visit during the treatment period. Change from extension baseline to EOT = last treatment period value in extension study - extension baseline value. | Baseline, End of treatment (5 years) | 
| Percent Brain Volume Change (PBVC) From Baseline at the End of Treatment | Brain volume was obtained by magnetic resonance imaging (MRI). Extension study baseline is defined as the measurement most immediately prior to or on the day of the first dose day of extension study. Brain volume changes very little over time. Hence, the PBVC at the end of treatment was calculated by adding up all the PBVC values from the scans performed during the extension treatment period. | Baseline and at end of treatment (Week 255) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Multiple sclerosis, ONO-4641, MSC2430913A, Efficacy