Phase 2 Extension Trial in Patients With Relapsing-Remitting Multiple Sclerosis (RRMS)
- Registration Number
- NCT01226745
- Lead Sponsor
- EMD Serono
- Brief Summary
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 \[NCT01081782\]).
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 340
- Completed 26 weeks of double-blind phase of Study ONO-4641POU006
- Presence of any dermatological abnormalities during Study ONO-4641POU006 that could increase the risk of the patient developing a skin cancer
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo - ONO4641 0.05 mg ONO-4641 - ONO-4641 0.10 mg - 0.10 mg ONO-4641 - Placebo - ONO4641 0.15 mg ONO-4641 - Placebo - ONO4641 0.10 mg ONO-4641 - ONO-4641 0.15 milligram (mg) - 0.15 mg ONO-4641 - ONO-4641 0.05 mg - 0.05 mg ONO-4641 -
- Primary Outcome Measures
Name Time Method Number of Subjects With Clinically Significant Abnormal Vital Signs Baseline up to Week 255 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.
Change From Baseline in Forced Expiratory Volume in One Second (FEV1) (Percent (%) Predicted Value) Baseline, Week 40, 52, 76, 100, 124, 148, early termination, Week 152, 200, early termination 2, Week 255 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.
Change From Baseline in Forced Vital Capacity (FVC) Baseline, Week 40, 52, 76, 100, 124, 148, early termination, Week 152, 200, early termination 2, Week 255 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.
Change From Baseline in Diffusing Capacity of Lung for Carbon Monoxide (DLCO) Baseline, Week 40, 52, early termination, Week 152, 200, 255 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.
Number of Subjects With Clinically Significant Abnormal Electrocardiogram (ECG) Measures Baseline up to Week 255 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.
Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination Baseline up to Week 255 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).
Number of Subjects With Clinically Significant Abnormalities in Dermatological Examination Baseline up to end of the treatment, assessed up to Week 255 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.
Number of Subjects With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, TEAEs Leading to Death and TEAEs Leading to Discontinuation 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 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.
- Secondary Outcome Measures
Name Time Method Number of Gadolinium (Gd)-Enhanced Lesions Baseline, Week 40, 52, 100, 148, early termination, Week 152, 200, early termination 2, Week 255 and end of treatment (5 years) 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.
Change From Baseline in Lesion Volume at the End of the Treatment (EoT) Baseline, End of treatment (5 years) 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.
Percent Brain Volume Change (PBVC) From Baseline at the End of Treatment Baseline and at end of treatment (Week 255) 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.
Trial Locations
- Locations (70)
Aurora Clinical Site 132
🇺🇸Aurora, Colorado, United States
Ormond Beach Clinical Site 129
🇺🇸Ormond Beach, Florida, United States
Sarasota Clinical Site 116
🇺🇸Sarasota, Florida, United States
Northbrook Clinical Site 135
🇺🇸Northbrook, Illinois, United States
Indianapolis Clinical Site 121
🇺🇸Indianapolis, Indiana, United States
Farmington Hills Clinical Site 126
🇺🇸Farmington Hills, Michigan, United States
Albuquerque Clinical Site 106
🇺🇸Albuquerque, New Mexico, United States
Rochester Clinical Site 108
🇺🇸Rochester, New York, United States
Charlotte Clinical Site 125
🇺🇸Charlotte, North Carolina, United States
Raleigh Clinical Site 103
🇺🇸Raleigh, North Carolina, United States
Round Rock Clinical Site 107
🇺🇸Round Rock, Texas, United States
Vancouver Clinical Site 131
🇨🇦Vancouver, British Columbia, Canada
Montreal Clinical Site 102
🇨🇦Montreal, Canada
Montreal Clinical Site 101
🇨🇦Montreal, Quebec, Canada
Pardubice Clinical Site 211
🇨🇿Pardubice, Czech Republic
Glessen Clinical Site 221
🇩🇪Glessen, Germany
Leipzig Clinical Site 229
🇩🇪Leipzig, Germany
Marburg Clinical Site 228
🇩🇪Marburg, Germany
Kanto Region Clinical Site 404
🇯🇵Kanto, Japan
Tubingen Clinical Site 226
🇩🇪Tubingen, Germany
Kinki Region Clinical Site 401
🇯🇵Kinki, Japan
Kinki Region Clinical Site 408
🇯🇵Kinki, Japan
Tohoku Region Clinical Site 410
🇯🇵Tohoku, Japan
Tohoku Region Clinical Site 403
🇯🇵Tohoku, Japan
Moscow Clinical Site 330
🇷🇺Moscow, Russian Federation
Nizhniy Novgorod Clinical Site 321
🇷🇺Nizhniy Novgorod, Russian Federation
Brugge Clinical Site 203
🇧🇪Brugge, Belgium
Olomouc Clinical Site 212
🇨🇿Olomouc, Czech Republic
Kanto Region Clinical Site 406
🇯🇵Kanto, Japan
Kanto Region Clinical Site 409
🇯🇵Kanto, Japan
Gdansk Clinical Site 302
🇵🇱Gdansk, Poland
Praha 5 Clinical Site 213
🇨🇿Praha 5, Czech Republic
Athens Clinical Site 243
🇬🇷Athens, Greece
La Louviere Clinical Site 201
🇧🇪La Louviere, Belgium
Kanto Region Clinical Site 405
🇯🇵Kanto, Japan
Lebanon Clinical Site 115
🇺🇸Lebanon, New Hampshire, United States
Gatineau Clinical Site 114
🇨🇦Gatineau, Quebec, Canada
Katowice Clinical Site 309
🇵🇱Katowice, Poland
Krakow Clinical Site 307
🇵🇱Krakow, Poland
Lodz Clinical Site 306
🇵🇱Lodz, Poland
Novosibirsk Clinical Site 324
🇷🇺Novosibirsk, Russian Federation
Detroit Clinical Site 104
🇺🇸Detroit, Michigan, United States
Barcelona Clinical Site 252
🇪🇸Barcelona, Spain
Fort Wayne Clinical Site 111
🇺🇸Fort Wayne, Indiana, United States
Fairfield Clinical Site 110
🇺🇸Fairfield, Connecticut, United States
Akron Clinical Site 112
🇺🇸Akron, Ohio, United States
Philadelphia Clinical Site 120
🇺🇸Philadelphia, Pennsylvania, United States
Knoxville Clinical Site 134
🇺🇸Knoxville, Tennessee, United States
Greenfield park Clinical Site 109
🇨🇦Greenfield Park, Quebec, Canada
Kinki Region Clinical Site 407
🇯🇵Kinki, Japan
Bialystok Clinical Site 305
🇵🇱Bialystok, Poland
Moscow Clinical Site 332
🇷🇺Moscow, Russian Federation
Plewiska Clinical Site 304
🇵🇱Plewiska, Poland
Warszawa Clinical Site 308
🇵🇱Warszawa, Poland
Hospitalet de Llobregat Clinical Site 251
🇪🇸Hospitalet de Llobregat, Spain
Sevilla Clinical Site 256
🇪🇸Sevilla, Spain
Czeladz Clinical Site 303
🇵🇱Czeladz, Poland
Kazan Clinical Site 333
🇷🇺Kazan, Russian Federation
Samara Clinical Site 329
🇷🇺Samara, Russian Federation
St. Petersburg Clinical Site 325
🇷🇺St. Petersburg, Russian Federation
Lviv Clinical Site 343
🇺🇦Lviv, Ukraine
Vinnytsya Clinical Site 342
🇺🇦Vinnytsya, Ukraine
Ufa Clinical Site 326
🇷🇺Ufa, Russian Federation
Barcelona Clinical Site 253
🇪🇸Barcelona, Spain
Kyiv Clinical Site 344
🇺🇦Kyiv, Ukraine
Girona Clinical Site 254
🇪🇸Girona, Spain
Bilbao Clinical Site 255
🇪🇸Bilbao, Spain
Dnipropetrovsk Clinical Site 341
🇺🇦Dnipropetrovsk, Ukraine
Fort Collins Clinical Site 123
🇺🇸Fort Collins, Colorado, United States
Tucson Clinical Site 133
🇺🇸Tucson, Arizona, United States