A Prospective Study Looking at the Use of Rebif® in Subjects With Clinically Isolated Syndrome (CIS-ON)

• ClinicalTrials.gov Identifier: NCT00287079
• Recruitment Status: Completed
• First Posted: February 6, 2006
• Results First Posted: April 4, 2012
• Last Update Posted: December 27, 2013
• Sponsor: Merck KGaA, Darmstadt, Germany
• Collaborator: EMD Serono Canada Inc.
• Information provided by (Responsible Party): Merck KGaA, Darmstadt, Germany

Tracking Information

• First Submitted Date: February 2, 2006
• First Posted Date: February 6, 2006
• Results First Submitted Date: February 2, 2012
• Results First Posted Date: April 4, 2012
• Last Update Posted Date: December 27, 2013
• Study Start Date: October 2005
• Actual Primary Completion Date: November 2008 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: March 7, 2012)

Time in Month to Clinical Definite Multiple Sclerosis (CDMS) From Kaplan-Meier Estimates [ Time Frame: Up to Week 96 ]

CDMS was defined by the occurrence of a second exacerbation or relapse over 96 weeks in participants who presented with Clinically Isolated Syndrome (CIS) accompanied by an abnormal Magnetic Resonance Imaging (MRI) scan. Time was calculated from the date of the stabilization of the baseline CIS episode to the qualifying relapse for the CDMS.

• Original Primary Outcome Measures: Not Provided

Current Secondary Outcome Measures (submitted: March 7, 2012)

• Percentage of Participants Who Converted to Clinical Definite Multiple Sclerosis (CDMS) [ Time Frame: Up to Week 96 ]
  CDMS was defined as the occurrence of a second exacerbation over 96 weeks in participants who presented with CIS accompanied by an abnormal MRI scan.
• Percentage of Participants With Adverse Events (AEs) or Serious Adverse Events (SAEs) [ Time Frame: Up to Week 96 ]
  AE: any new untoward medical occurrence/worsening of pre-existing medical condition, whether or not related to study drug. SAE: any AE that resulted in death; was life threatening; resulted in persistent/significant disability/incapacity; resulted in/prolonged an existing in-patient hospitalization; was a congenital anomaly/birth defect; or was a medically important condition.

• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Prospective Study Looking at the Use of Rebif® in Subjects With Clinically Isolated Syndrome
• Official Title: A Prospective, Open Label, Multi-centre Study Exploring the Use of Subcutaneous (sc) 44 Microgram Interferon (IFN) Beta - 1a (Rebif®) Once a Week (qw) in Subjects With Clinically Isolated Syndrome (CIS)

Brief Summary

The primary objective of this initiative is to assess the effectiveness of subcutaneous (sc) interferon (IFN) beta - 1a, (Rebif®), versus No Treatment in delaying the conversion to Clinically Definite Multiple Sclerosis (CDMS) - as defined by the occurrence of a second exacerbation - over 96 weeks in subjects that present with Clinically Isolated Syndrome (CIS) accompanied by an abnormal magnetic resonance imaging (MRI). The secondary objectives are to:

• Assess the effectiveness of sc IFN beta - 1a (Rebif®) therapy in reducing the proportion of patients with CIS converting to CDMS
• Assess the safety of sc IFN beta - 1a (Rebif®) in the patients with CIS

• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Clinically Isolated Syndrome

Intervention

• Drug: Rebif®
  44 microgram (mcg) IFN beta-1a sc once a week (qw) for 96 weeks
• Other: No Treatment
  No treatment for 96 weeks

Study Arms

• Experimental: Rebif®
  Intervention: Drug: Rebif®
• No Treatment
  Intervention: Other: No Treatment

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: March 7, 2012): 35
• Original Enrollment: Not Provided
• Actual Study Completion Date: November 2008
• Actual Primary Completion Date: November 2008 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Subject must have experienced a first clinical episode suggestive of demyelinating disease
• Subject must present with an abnormal MRI displaying at least 3 T2 weighted hyperintense lesions typical of multiple sclerosis (MS)
• Subject must be greater than or equal to 18 years old
• Subject must have had onset of the clinical attack within the last 120 days
• Subject must give written informed consent
• Female subjects must be neither pregnant nor breast feeding, and must not be of child-bearing potential as defined by either:
• Being post-menopausal or surgically sterile
• Using hormonal contraceptive, intra-uterine device, diaphragm with spermicide or condom with spermicide for the duration of the study

Subjects electing treatment:

• Subject must be eligible for Interferon-beta 1-a therapy

Exclusion Criteria:

• Subject has evidence of other neurological diseases that could explain his/her symptomatology
• Subject is pregnant or in lactation
• Subject suffers from an intercurrent autoimmune disease
• Subject suffers from major medical or psychiatric illness that in the opinion of the investigator creates undue risk to the subject or could affect compliance with the procedures required by this study
• Subject has received immunomodulatory or immunosuppressive therapy (including but not limited to cyclophosphamide, cyclosporine, methotrexate, azathioprine, linomide, mitoxantrone, teriflunomide, natalizumab, laquinimod, campath), within 12 months of study day 1

Subjects electing treatment:

• Subject has inadequate liver function, defined by total bilirubin, aspartate transaminase (AST), alanine aminotransferase (ALT), or alkaline phosphatase > 2.5 times the upper limit of normal values
• Subject has inadequate bone marrow reserve, defined as white blood cell count less than 0.5 times the lower limit of normal
• Subject has a known allergy to IFN or any of the excipients of the drug product

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Months to 65 Years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Canada

Administrative Information

• NCT Number: NCT00287079
• Other Study ID Numbers: IMP 26222
• Has Data Monitoring Committee: Not Provided
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: Merck KGaA, Darmstadt, Germany
• Study Sponsor: Merck KGaA, Darmstadt, Germany
• Collaborators: EMD Serono Canada Inc.

Investigators

• Study Director: Medical Director; EMD Serono Canada Inc.

• PRS Account: Merck KGaA, Darmstadt, Germany
• Verification Date: December 2013