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

  Show 70 Study Locations
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 August 23, 2016