Clinical trial NCT00110396: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Multiple Sclerosis
Keywords: Multiple Sclerosis
Relapsing forms of multiple sclerosis
Lead sponsor: EMD Serono
Sponsor class: INDUSTRY
Collaborators: name: Pfizer
First posted: 2005-05-09
Enrollment: 260
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Number of Participants Who Were Neutralising Antibody (NAb) Positive at the Week 96 Visit.
timeFrame: 96 weeks
Secondary outcomes:
measure: Number of Participants Who Were Neutralising Antibody (NAb) Positive at Anytime During the Study
timeFrame: 96 weeks
measure: Number of Participants With Binding Antibodies (BAb) at Week 96
timeFrame: 96 weeks
Other outcomes:
Locations:
city: Rockland
country: United States
facility: Local US Medical Information
state: Massachusetts
Study officials:
affiliation: Merck Serono SA - Geneva
name: Bettina Stubinski, MD
role: STUDY_DIRECTOR
References:
citation: Giovannoni G, Barbarash O, Casset-Semanaz F, Jaber A, King J, Metz L, Pardo G, Simsarian J, Sorensen 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. doi: 10.1016/j.clinthera.2007.06.002.
citation: Giovannoni G, Barbarash O, Casset-Semanaz F, King J, Metz L, Pardo G, Simsarian J, Sorensen 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.