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

Study Overview
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Brief Summary
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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
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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.

Official Title
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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

Conditions
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Multiple Sclerosis

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


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Rebif New Formulation Cohort<br> | Biological: Interferon-beta-1a FBS-free/HSA-free<br>* Pre-filled syringes 44mcg/injected subcutaneous 3x per week. Total study period is 96 weeks.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants Who Were Neutralising Antibody (NAb) Positive at the Week 96 Visit. | The NAb positive value was defined as NAb value greater or equal to 20 NU/mL. NAbs were detected using a viral cytopathic assay. | 96 weeks | 

Secondary Outcome Measures

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

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Multiple Sclerosis, Relapsing forms of multiple sclerosis