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

Primary Purpose

Multiple Sclerosis

Status
Completed
Phase
Phase 3
Locations
United States
Study Type
Interventional
Intervention
Interferon-beta-1a FBS-free/HSA-free
Sponsored by
EMD Serono
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Multiple Sclerosis focused on measuring Multiple Sclerosis, Relapsing forms of multiple sclerosis

Eligibility Criteria

18 Years - 60 Years (Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Local US Medical Information

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Rebif New Formulation Cohort

Arm Description

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.
Number of Participants With Binding Antibodies (BAb) at Week 96
Presence of BAbs. BAbs were measured by ELISA (Enzyme-linked immunosorbent assay).

Full Information

First Posted
May 6, 2005
Last Updated
June 18, 2015
Sponsor
EMD Serono
Collaborators
Pfizer
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1. Study Identification

Unique Protocol Identification Number
NCT00110396
Brief Title
Rebif New Formulation (RNF) in Relapsing Forms of Multiple Sclerosis
Acronym
RNF
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

2. Study Status

Record Verification Date
June 2015
Overall Recruitment Status
Completed
Study Start Date
January 2005 (undefined)
Primary Completion Date
April 2007 (Actual)
Study Completion Date
April 2007 (Actual)

3. Sponsor/Collaborators

Name of the Sponsor
EMD Serono
Collaborators
Pfizer

4. Oversight

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Multiple Sclerosis
Keywords
Multiple Sclerosis, Relapsing forms of multiple sclerosis

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
260 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Rebif New Formulation Cohort
Arm Type
Experimental
Intervention Type
Biological
Intervention Name(s)
Interferon-beta-1a FBS-free/HSA-free
Intervention Description
Pre-filled syringes 44mcg/injected subcutaneous 3x per week. Total study period is 96 weeks.
Primary Outcome Measure Information:
Title
Number of Participants Who Were Neutralising Antibody (NAb) Positive at the Week 96 Visit.
Description
The NAb positive value was defined as NAb value greater or equal to 20 NU/mL. NAbs were detected using a viral cytopathic assay.
Time Frame
96 weeks
Secondary Outcome Measure Information:
Title
Number of Participants Who Were Neutralising Antibody (NAb) Positive at Anytime During the Study
Description
The NAb positive value was defined as NAb value greater or equal to 20 NU/mL. NAbs were detected using a viral cytopathic assay.
Time Frame
96 weeks
Title
Number of Participants With Binding Antibodies (BAb) at Week 96
Description
Presence of BAbs. BAbs were measured by ELISA (Enzyme-linked immunosorbent assay).
Time Frame
96 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
60 Years
Accepts Healthy Volunteers
No
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Bettina Stubinski, MD
Organizational Affiliation
Merck Serono SA - Geneva
Official's Role
Study Director
Facility Information:
Facility Name
Local US Medical Information
City
Rockland
State/Province
Massachusetts
ZIP/Postal Code
02370
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
17692727
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.
Results Reference
result
PubMed Identifier
18755819
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.
Results Reference
result
Links:
URL
http://www.mslifelines.com
Description
Full FDA approved prescribing information can be found here

Learn more about this trial

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

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