Rebif New Formulation (RNF) in Relapsing Forms of Multiple Sclerosis (RNF)

• ClinicalTrials.gov Identifier: NCT00110396
• Recruitment Status: Completed
• First Posted: May 9, 2005
• Results First Posted: July 9, 2010
• Last Update Posted: July 15, 2015
• Sponsor: EMD Serono
• Collaborator: Pfizer
• Information provided by: EMD Serono

Tracking Information

• First Submitted Date: May 6, 2005
• First Posted Date: May 9, 2005
• Results First Submitted Date: April 30, 2010
• Results First Posted Date: July 9, 2010
• Last Update Posted Date: July 15, 2015
• Study Start Date: January 2005
• Actual Primary Completion Date: April 2007 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: June 14, 2010)

Number of Participants Who Were Neutralising Antibody (NAb) Positive at the Week 96 Visit. [ Time Frame: 96 weeks ]

The NAb positive value was defined as NAb value greater or equal to 20 NU/mL. NAbs were detected using a viral cytopathic assay.

• Original Primary Outcome Measures: Not Provided

Current Secondary Outcome Measures (submitted: June 14, 2010)

• Number of Participants Who Were Neutralising Antibody (NAb) Positive at Anytime During the Study [ Time Frame: 96 weeks ]
  The NAb positive value was defined as NAb value greater or equal to 20 NU/mL. NAbs were detected using a viral cytopathic assay.
• Number of Participants With Binding Antibodies (BAb) at Week 96 [ Time Frame: 96 weeks ]
  Presence of BAbs. BAbs were measured by ELISA (Enzyme-linked immunosorbent assay).

• 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: Rebif New Formulation (RNF) in Relapsing Forms of Multiple Sclerosis
• Official Title: A Multicentre, Single Arm, Open-Label, Phase IIIB Study to Evaluate the Safety and Antigenicity of Rebif® (Interferon-beta-1a) in Subjects With Relapsing Forms of Multiple Sclerosis
• Brief Summary: The primary objective of the study is to compare the immunogenicity of the new fetal bovine serum (FBS)-free/human serum albumin (HSA)-free Rebif® formulation (RNF) to historical data.
• Detailed Description: As has been seen with other recombinant protein molecules, the use of injectable recombinant proteins may result in the development of neutralising antibodies (NAbs). Antibodies are considered neutralising by their ability to inhibit the biological effect of interferon in a bioassay system. EMD Serono has actively pursued improvements in the formulation of interferon (IFN) beta-1a to reduce aggregate levels and to develop a formulation that is HSA-free. Reducing aggregates should reduce antigenicity of the product while removal of HSA may have an unpredictable effect on antigenicity. EMD Serono will conduct a study to assess the immunogenicity and safety of the new HSA-free formulation, manufactured using IFN-ß-1a drug substance produced by a new clone from the FBS-free process.
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Non-Randomized; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Multiple Sclerosis

Intervention

Biological: Interferon-beta-1a FBS-free/HSA-free

Pre-filled syringes 44mcg/injected subcutaneous 3x per week. Total study period is 96 weeks.

Study Arms

Experimental: Rebif New Formulation Cohort

Intervention: Biological: Interferon-beta-1a FBS-free/HSA-free

Publications *

• Giovannoni G, Barbarash O, Casset-Semanaz F, Jaber A, King J, Metz L, Pardo G, Simsarian J, Sørensen PS, Stubinski B; RNF Study Group. Immunogenicity and tolerability of an investigational formulation of interferon-beta1a: 24- and 48-week interim analyses of a 2-year, single-arm, historically controlled, phase IIIb study in adults with multiple sclerosis. Clin Ther. 2007 Jun;29(6):1128-45.
• Giovannoni G, Barbarash O, Casset-Semanaz F, King J, Metz L, Pardo G, Simsarian J, Sørensen PS, Stubinski B; Rebif New Formulation Study Group. Safety and immunogenicity of a new formulation of interferon beta-1a (Rebif New Formulation) in a Phase IIIb study in patients with relapsing multiple sclerosis: 96-week results. Mult Scler. 2009 Feb;15(2):219-28. doi: 10.1177/1352458508097299. Epub 2008 Aug 28.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: June 14, 2010): 260
• Original Enrollment (submitted: June 23, 2005): 230
• Actual Study Completion Date: April 2007
• Actual Primary Completion Date: April 2007 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Participant has a relapsing form of Multiple Sclerosis (MS); diagnosis of MS is in accordance with the McDonald criteria
• Participant is eligible for interferon therapy
• Participant is between 18 and 60 years old
• Participant has an Expanded Disability Status Scale (EDSS) < 6.0.
• Participant is willing to follow study procedures
• Participant has given written informed consent
• Female participants must be neither pregnant nor breast-feeding, and must lack childbearing potential, as defined by either:
• Being post-menopausal or surgically sterile, or
• Using a hormonal contraceptive, intra-uterine device, diaphragm with spermicide or condom with spermicide for the duration of the study.
• Confirmation that the participant is not pregnant must be established by a negative serum or urinary hCG test within 7 days prior to start of study treatment. A pregnancy test is not required if the participant is post-menopausal or surgically sterile.

Exclusion Criteria:

• Participant has a Clinically Isolated Syndrome (CIS), Primary Progressive MS, or Secondary Progressive MS without superimposed relapses.
• Participant had any prior interferon beta therapy (either beta-1b or beta-1a)
• Participant has an ongoing MS relapse.
• Participant received any other approved disease modifying therapy for MS (e.g. glatiramer acetate) or any cytokine or anti-cytokine therapy within the 3 months prior to Study Day 1(SD1).
• Participant had prior use of cladribine or has previously received total lymphoid irradiation.
• Participant received oral or systemic corticosteroids or adrenocorticotropic hormone (ACTH) within 30 days of SD1.
• Participant received intravenous immunoglobulins or underwent plasmapheresis within the 6 months prior to SD1.
• Participant received immunomodulatory or immunosuppressive therapy (including but not limited to cyclophosphamide, cyclosporin, methotrexate, azathioprine, linomide, mitoxantrone, teriflunomide, natalizumab, laquinimod, Campath) within the 12 months prior to SD1.
• Participant requires chronic or monthly pulse corticosteroids during the study.
• Participant received any investigational drug or experimental procedure within 12 weeks of SD1.
• Participant has inadequate liver function, defined by a total bilirubin, aspartate aminotransferase (AST) or alanine aminotransferase (ALT) or alkaline phosphatase > 2.5 times the upper limit of the normal values.
• Participant has inadequate bone marrow reserve, defined as a white blood cell count less than 0.5 x lower limit of normal.
• Participant suffers from current autoimmune disease.
• Participant 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 study protocol.
• Participant has a known allergy to IFN or the excipients.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 60 Years (Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT00110396
• Other Study ID Numbers: 25632
• Has Data Monitoring Committee: Not Provided
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: Susan Fischer, EMD Serono Inc
• Study Sponsor: EMD Serono
• Collaborators: Pfizer

Investigators

• Study Director: Bettina Stubinski, MD; Merck Serono SA - Geneva

• PRS Account: EMD Serono
• Verification Date: June 2015