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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
Results First Received: January 31, 2016  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Double Blind (Subject, Investigator);   Primary Purpose: Treatment
Condition: Multiple Sclerosis
Intervention: Drug: ONO-4641

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
No text entered.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
One Subject received 0.15 mg of ONO-4641 instead of placebo in error in the core trial and was subsequently re-randomized during the extension trial and received 0.10 mg of ONO-4641.This subject was not reported in the participant flow for the study.

Reporting Groups
  Description
ONO-4641 0.15 Milligram (mg) - 0.15 mg Subjects who were administered with ONO-4641 at a dose of 0.15 mg in the core study were administered with ONO-4641 at a dose of 0.15 mg once daily in the extension study for a duration of 225 weeks.
ONO-4641 0.10 mg - 0.10 mg Subjects who were administered with ONO-4641 at a dose of 0.10 mg in the core study were administered with ONO-4641 at a dose of 0.10 mg once daily in the extension study for a duration of 225 weeks.
ONO-4641 0.05 mg - 0.05 mg Subjects who were administered with ONO-4641 at a dose of 0.05 mg in the core study were administered with ONO-4641 at a dose of 0.05 mg once daily in the extension study for a duration of 225 weeks.
Placebo - ONO4641 0.15 mg Subjects who were administered with placebo in the core study were administered with ONO-4641 at a dose of 0.15 mg once daily in the extension study for a duration of 225 weeks.
Placebo - ONO4641 0.10 mg Subjects who were administered with placebo in the core study were administered with ONO-4641 at a dose of 0.10 mg once daily in the extension study for a duration of 225 weeks.
Placebo - ONO4641 0.05 mg Subjects who were administered with placebo in the core study were administered with ONO-4641 at a dose of 0.05 mg once daily in the extension study for a duration of 225 weeks.

Participant Flow:   Overall Study
    ONO-4641 0.15 Milligram (mg) - 0.15 mg   ONO-4641 0.10 mg - 0.10 mg   ONO-4641 0.05 mg - 0.05 mg   Placebo - ONO4641 0.15 mg   Placebo - ONO4641 0.10 mg   Placebo - ONO4641 0.05 mg
STARTED   80   87   89   29   26   29 
COMPLETED   63   71   69   24   22   24 
NOT COMPLETED   17   16   20   5   4   5 
Did not complete schedule of assessments                8                3                6                0                0                1 
Lost to Follow-up                2                6                6                1                1                2 
Death                1                0                0                0                0                1 
Unspecified                6                7                8                4                3                1 



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Safety analysis set consisted of all the enrolled subjects.

Reporting Groups
  Description
ONO-4641 0.15 mg - 0.15 mg Subjects who were administered with ONO-4641 at a dose of 0.15 mg in the core study were administered with ONO-4641 at a dose of 0.15 mg once daily in the extension study for a duration of 225 weeks.
ONO-4641 0.10 mg - 0.10 mg Subjects who were administered with ONO-4641 at a dose of 0.10 mg in the core study were administered with ONO-4641 at a dose of 0.10 mg once daily in the extension study for a duration of 225 weeks.
ONO-4641 0.05 mg - 0.05 mg Subjects who were administered with ONO-4641 at a dose of 0.05 mg in the core study were administered with ONO-4641 at a dose of 0.05 mg once daily in the extension study for a duration of 225 weeks.
Placebo - ONO4641 0.15 mg Subjects who were administered with placebo in the core study were administered with ONO-4641 at a dose of 0.15 mg once daily in the extension study for a duration of 225 weeks.
Placebo - ONO4641 0.10 mg Subjects who were administered with placebo in the core study were administered with ONO-4641 at a dose of 0.10 mg once daily in the extension study for a duration of 225 weeks.
Placebo - ONO4641 0.05 mg Subjects who were administered with placebo in the core study were administered with ONO-4641 at a dose of 0.05 mg once daily in the extension study for a duration of 225 weeks.
Total Total of all reporting groups

Baseline Measures
   ONO-4641 0.15 mg - 0.15 mg   ONO-4641 0.10 mg - 0.10 mg   ONO-4641 0.05 mg - 0.05 mg   Placebo - ONO4641 0.15 mg   Placebo - ONO4641 0.10 mg   Placebo - ONO4641 0.05 mg   Total 
Overall Participants Analyzed 
[Units: Participants]
 80   87   89   29   26   29   340 
Age 
[Units: Years]
Mean (Standard Deviation)
 36.3  (8.47)   36.0  (8.64)   38.2  (8.66)   35.6  (9.59)   37.0  (6.96)   38.7  (9.48)   36.9  (8.66) 
Gender 
[Units: Subjects]
             
Female   53   74   66   18   17   24   252 
Male   27   13   23   11   9   5   88 


  Outcome Measures
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1.  Primary:   Number of Subjects With Clinically Significant Abnormal Vital Signs   [ Time Frame: Baseline up to Week 255 ]

2.  Primary:   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 ]

3.  Primary:   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 ]

4.  Primary:   Change From Baseline in Diffusing Capacity of Lung for Carbon Monoxide (DLCO)   [ Time Frame: Baseline, Week 40, 52, early termination, Week 152, 200, 255 ]

5.  Primary:   Number of Subjects With Clinically Significant Abnormal Electrocardiogram (ECG) Measures   [ Time Frame: Baseline up to Week 255 ]

6.  Primary:   Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination   [ Time Frame: Baseline up to Week 255 ]

7.  Primary:   Number of Subjects With Clinically Significant Abnormalities in Dermatological Examination   [ Time Frame: Baseline up to end of the treatment, assessed up to Week 255 ]

8.  Primary:   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 ]

9.  Secondary:   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) ]

10.  Secondary:   Change From Baseline in Lesion Volume at the End of the Treatment (EoT)   [ Time Frame: Baseline, End of treatment (5 years) ]

11.  Secondary:   Percent Brain Volume Change (PBVC) From Baseline at the End of Treatment   [ Time Frame: Baseline and at end of treatment (Week 255) ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
Company has decided to not pursue phase 3 development of ceralifimod (ONO-4641). The decision was not related to any safety and efficacy findings.


  More Information
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Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Results Point of Contact:  
Name/Title: Merck KGaA Communication Center
Organization: Merck Healthcare, a business of Merck KGaA, Darmstadt, Germany
phone: +49-6151-72-5200
e-mail: service@merckgroup.com


Publications of Results:
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 ( EudraCT Number )
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