Trial record 1 of 2 for:    ONO-4641
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Phase 2 Extension Trial in Patients With Relapsing-Remitting Multiple Sclerosis (RRMS) (DreaMS)

This study has been terminated.
(Merck has decided to not pursue phase 3 development of ceralifimod (ONO-4641). The decision was not related to any safety and efficacy findings)
Sponsor:
Collaborators:
Merck KGaA
Ono Pharmaceutical Co. Ltd
Information provided by (Responsible Party):
EMD Serono
ClinicalTrials.gov Identifier:
NCT01226745
First received: October 19, 2010
Last updated: June 2, 2016
Last verified: June 2016
  Purpose
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]).

Condition Intervention Phase
Multiple Sclerosis
Drug: ONO-4641
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: A Safety and Efficacy Extension Study of ONO-4641 (MSC2430913A) in Patients With Relapsing-Remitting Multiple Sclerosis

Resource links provided by NLM:


Further study details as provided by EMD Serono:

Primary Outcome Measures:
  • Number of Subjects With Clinically Significant Abnormal Vital Signs [ Time Frame: Baseline up to Week 255 ] [ Designated as safety issue: Yes ]
    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) [ Time Frame: Baseline, Week 40, 52, 76, 100, 124, 148, early termination, Week 152, 200, early termination 2, Week 255 ] [ Designated as safety issue: Yes ]
    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) [ Time Frame: Baseline, Week 40, 52, 76, 100, 124, 148, early termination, Week 152, 200, early termination 2, Week 255 ] [ Designated as safety issue: Yes ]
    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) [ Time Frame: Baseline, Week 40, 52, early termination, Week 152, 200, 255 ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: Baseline up to Week 255 ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: Baseline up to Week 255 ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: Baseline up to end of the treatment, assessed up to Week 255 ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: 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 ] [ Designated as safety issue: Yes ]
    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:
  • Number of Gadolinium (Gd)-Enhanced Lesions [ Time Frame: Baseline, Week 40, 52, 100, 148, early termination, Week 152, 200, early termination 2, Week 255 and end of treatment (5 years) ] [ Designated as safety issue: No ]
    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) [ Time Frame: Baseline, End of treatment (5 years) ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: Baseline and at end of treatment (Week 255) ] [ Designated as safety issue: Yes ]
    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.


Enrollment: 340
Study Start Date: October 2010
Study Completion Date: January 2015
Primary Completion Date: January 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: ONO-4641 0.15 milligram (mg) - 0.15 mg Drug: ONO-4641
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.
Other Names:
  • MSC2430913A
  • Ceralifimod
Experimental: ONO-4641 0.10 mg - 0.10 mg Drug: ONO-4641
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.
Other Names:
  • MSC2430913A
  • Ceralifimod
Experimental: ONO-4641 0.05 mg - 0.05 mg Drug: ONO-4641
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.
Other Names:
  • MSC2430913A
  • Ceralifimod
Experimental: Placebo - ONO4641 0.15 mg Drug: ONO-4641
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.
Other Names:
  • MSC2430913A
  • Ceralifimod
Experimental: Placebo - ONO4641 0.10 mg Drug: ONO-4641
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.
Other Names:
  • MSC2430913A
  • Ceralifimod
Experimental: Placebo - ONO4641 0.05 mg Drug: ONO-4641
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.
Other Names:
  • MSC2430913A
  • Ceralifimod

  Eligibility

Ages Eligible for Study:   18 Years to 55 Years   (Adult)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01226745

  Hide Study Locations
Locations
United States, Arizona
Tucson Clinical Site 133
Tucson, Arizona, United States, 85705
United States, Colorado
Aurora Clinical Site 132
Aurora, Colorado, United States, 80045
Fort Collins Clinical Site 123
Fort Collins, Colorado, United States, 80528
United States, Connecticut
Fairfield Clinical Site 110
Fairfield, Connecticut, United States, 06824
United States, Florida
Ormond Beach Clinical Site 129
Ormond Beach, Florida, United States, 32174
Sarasota Clinical Site 116
Sarasota, Florida, United States, 34243
United States, Illinois
Northbrook Clinical Site 135
Northbrook, Illinois, United States, 60062
United States, Indiana
Fort Wayne Clinical Site 111
Fort Wayne, Indiana, United States, 46805
Indianapolis Clinical Site 121
Indianapolis, Indiana, United States, 46202
United States, Michigan
Detroit Clinical Site 104
Detroit, Michigan, United States, 48202
Farmington Hills Clinical Site 126
Farmington Hills, Michigan, United States, 48334
United States, New Hampshire
Lebanon Clinical Site 115
Lebanon, New Hampshire, United States, 03756
United States, New Mexico
Albuquerque Clinical Site 106
Albuquerque, New Mexico, United States, 87131
United States, New York
Rochester Clinical Site 108
Rochester, New York, United States, 14642
United States, North Carolina
Charlotte Clinical Site 125
Charlotte, North Carolina, United States, 28201
Raleigh Clinical Site 103
Raleigh, North Carolina, United States, 27607
United States, Ohio
Akron Clinical Site 112
Akron, Ohio, United States, 44320
United States, Pennsylvania
Philadelphia Clinical Site 120
Philadelphia, Pennsylvania, United States, 19104
United States, Tennessee
Knoxville Clinical Site 134
Knoxville, Tennessee, United States, 37934
United States, Texas
Round Rock Clinical Site 107
Round Rock, Texas, United States, 78681
Belgium
Brugge Clinical Site 203
Brugge, Belgium, 8000
La Louviere Clinical Site 201
La Louviere, Belgium, 8000
Canada, British Columbia
Vancouver Clinical Site 131
Vancouver, British Columbia, Canada, V6T 2B5
Canada, Quebec
Gatineau Clinical Site 114
Gatineau, Quebec, Canada
Greenfield park Clinical Site 109
Greenfield Park, Quebec, Canada, J4V2J2
Montreal Clinical Site 101
Montreal, Quebec, Canada, H1T2M4
Canada
Montreal Clinical Site 102
Montreal, Canada, H9X3Z9
Czech Republic
Olomouc Clinical Site 212
Olomouc, Czech Republic, 775 20
Pardubice Clinical Site 211
Pardubice, Czech Republic, 53203
Praha 5 Clinical Site 213
Praha 5, Czech Republic, 15006
Germany
Glessen Clinical Site 221
Glessen, Germany, 35385
Leipzig Clinical Site 229
Leipzig, Germany, 04103
Marburg Clinical Site 228
Marburg, Germany, 35033
Tubingen Clinical Site 226
Tubingen, Germany, 72076
Greece
Athens Clinical Site 243
Athens, Greece, 115 29
Japan
Kanto Region Clinical Site 404
Kanto, Japan
Kanto Region Clinical Site 405
Kanto, Japan
Kanto Region Clinical Site 406
Kanto, Japan
Kanto Region Clinical Site 409
Kanto, Japan
Kinki Region Clinical Site 407
Kinki, Japan
Kinki Region Clinical Site 408
Kinki, Japan
Kinki Region Clinical Site 401
Kinki, Japan
Tohoku Region Clinical Site 410
Tohoku, Japan
Tohoku Region Clinical Site 403
Tohoku, Japan
Poland
Bialystok Clinical Site 305
Bialystok, Poland, 15-402
Czeladz Clinical Site 303
Czeladz, Poland, 41-250
Gdansk Clinical Site 302
Gdansk, Poland, 80-803
Katowice Clinical Site 309
Katowice, Poland, 40-594
Krakow Clinical Site 307
Krakow, Poland, 31-530
Lodz Clinical Site 306
Lodz, Poland, 90-153
Plewiska Clinical Site 304
Plewiska, Poland, 62-064
Warszawa Clinical Site 308
Warszawa, Poland, 04-749
Russian Federation
Kazan Clinical Site 333
Kazan, Russian Federation, 420103
Moscow Clinical Site 330
Moscow, Russian Federation, 121356
Moscow Clinical Site 332
Moscow, Russian Federation, 107150
Nizhniy Novgorod Clinical Site 321
Nizhniy Novgorod, Russian Federation, 107150
Novosibirsk Clinical Site 324
Novosibirsk, Russian Federation, 630091
Samara Clinical Site 329
Samara, Russian Federation, 443095
St. Petersburg Clinical Site 325
St. Petersburg, Russian Federation, 194354
Ufa Clinical Site 326
Ufa, Russian Federation, 450005
Spain
Barcelona Clinical Site 253
Barcelona, Spain, 08025
Barcelona Clinical Site 252
Barcelona, Spain, 08025
Bilbao Clinical Site 255
Bilbao, Spain, 48013
Girona Clinical Site 254
Girona, Spain, 17007
Hospitalet de Llobregat Clinical Site 251
Hospitalet de Llobregat, Spain, 08907
Sevilla Clinical Site 256
Sevilla, Spain, 41071
Ukraine
Dnipropetrovsk Clinical Site 341
Dnipropetrovsk, Ukraine, 49027
Kyiv Clinical Site 344
Kyiv, Ukraine, 03110
Lviv Clinical Site 343
Lviv, Ukraine, 03110
Vinnytsya Clinical Site 342
Vinnytsya, Ukraine, 21005
Sponsors and Collaborators
EMD Serono
Merck KGaA
Ono Pharmaceutical Co. Ltd
Investigators
Study Director: Medical Responsible EMD Serono Inc., an affiliate of Merck KGaA, Darmstadt, Germany
Study Director: Medical Responsible Ono Pharmaceutical Co. Ltd
  More Information

Additional Information:
Publications:
Effect of Ceralifimod (ONO-4641), a Sphingosine-1-Phosphate Receptor-1 and -5 Agonist, on Magnetic Resonance Imaging Outcomes in Patients with Multiple Sclerosis: Interim Results from the Extension of the DreaMS Study (P3.161) Amit Bar-Or, Frauke Zipp, Matthew Scaramozza, Timothy Vollmer, Bryan Due, Karthinathan Thangavelu, Tanya Fischer, and Krzysztof Selmaj April 8, 2014 82:10 Supplement P3.161; 1526-632X

Responsible Party: EMD Serono
ClinicalTrials.gov Identifier: NCT01226745     History of Changes
Other Study ID Numbers: ONO-4641POU007 (EMR200559-002)  2010-018705-11 
Study First Received: October 19, 2010
Results First Received: January 31, 2016
Last Updated: June 2, 2016
Health Authority: United States: Food and Drug Administration
Belgium: Federal Agency for Medicinal Products and Health Products
Canada: Health Canada
Czech Republic: State Institute for Drug Control
Poland: Ministry of Health
Spain: Ministry of Health
Japan: Ministry of Health, Labor and Welfare
Germany: Federal Institute for Drugs and Medical Devices
Greece: National Organization of Medicines
Russia: Ministry of Health of the Russian Federation
Ukraine: Ministry of Health

Keywords provided by EMD Serono:
Multiple sclerosis
ONO-4641
MSC2430913A
Efficacy

Additional relevant MeSH terms:
Sclerosis
Multiple Sclerosis
Multiple Sclerosis, Relapsing-Remitting
Pathologic Processes
Demyelinating Autoimmune Diseases, CNS
Autoimmune Diseases of the Nervous System
Nervous System Diseases
Demyelinating Diseases
Autoimmune Diseases
Immune System Diseases

ClinicalTrials.gov processed this record on July 26, 2016