- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00110396
Rebif New Formulation (RNF) in Relapsing Forms of Multiple Sclerosis (RNF)
June 18, 2015 updated by: EMD Serono
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
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.
Study Overview
Status
Completed
Conditions
Intervention / Treatment
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
Enrollment (Actual)
260
Phase
- Phase 3
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
-
-
Massachusetts
-
Rockland, Massachusetts, United States, 02370
- Local US Medical Information
-
-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years to 60 years (Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
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.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Non-Randomized
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Rebif New Formulation Cohort
|
Pre-filled syringes 44mcg/injected subcutaneous 3x per week.
Total study period is 96 weeks.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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.
|
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
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.
|
96 weeks
|
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).
|
96 weeks
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Collaborators
Investigators
- Study Director: Bettina Stubinski, MD, Merck Serono SA - Geneva
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
General Publications
- 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.
- 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.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start
January 1, 2005
Primary Completion (Actual)
April 1, 2007
Study Completion (Actual)
April 1, 2007
Study Registration Dates
First Submitted
May 6, 2005
First Submitted That Met QC Criteria
May 6, 2005
First Posted (Estimate)
May 9, 2005
Study Record Updates
Last Update Posted (Estimate)
July 15, 2015
Last Update Submitted That Met QC Criteria
June 18, 2015
Last Verified
June 1, 2015
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Pathologic Processes
- Nervous System Diseases
- Immune System Diseases
- Demyelinating Autoimmune Diseases, CNS
- Autoimmune Diseases of the Nervous System
- Demyelinating Diseases
- Autoimmune Diseases
- Multiple Sclerosis
- Sclerosis
- Physiological Effects of Drugs
- Anti-Infective Agents
- Antiviral Agents
- Antineoplastic Agents
- Immunologic Factors
- Adjuvants, Immunologic
- Interferons
- Interferon beta-1a
- Interferon-beta
Other Study ID Numbers
- 25632
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Multiple Sclerosis
-
University Hospital, Basel, SwitzerlandSwiss National Science FoundationRecruitingMultiple Sclerosis (MS) | Relapsing-remitting Multiple Sclerosis (RRMS) | Secondary-progressive Multiple Sclerosis (SPMS) | Primary Progressive Multiple Sclerosis (PPMS)Switzerland
-
University of California, Los AngelesUnknownRelapsing-remitting Multiple Sclerosis | Secondary-progressive Multiple Sclerosis | Primary-progressive Multiple SclerosisUnited States
-
BiogenCompletedMultiple Sclerosis | Relapsing-Remitting Multiple Sclerosis | Secondary Progressive Multiple Sclerosis | Multiple Sclerosis, Primary Progressive | Multiple Sclerosis, Remittent ProgressiveJapan
-
The Cleveland ClinicUniversity Hospitals Cleveland Medical CenterCompletedRelapsing-Remitting Multiple Sclerosis | Secondary Progressive Multiple Sclerosis | Progressive Relapsing Multiple SclerosisUnited States
-
Rigshospitalet, DenmarkOdense University Hospital; Aarhus University Hospital; Hvidovre University Hospital and other collaboratorsActive, not recruitingRelapsing Remitting Multiple Sclerosis | Primary Progressive Multiple Sclerosis | Secondary Progressive Multiple SclerosisDenmark
-
Queen Mary University of LondonTakeda Pharmaceuticals International, Inc.RecruitingRelapsing Remitting Multiple Sclerosis | Primary Progressive Multiple Sclerosis | Secondary Progressive Multiple SclerosisUnited Kingdom
-
Icahn School of Medicine at Mount SinaiColumbia University; New York Stem Cell Foundation Research InstituteCompletedClinically Isolated Syndrome | Relapsing-Remitting Multiple Sclerosis | Primary Progressive Multiple Sclerosis | Secondary Progressive Multiple SclerosisUnited States
-
Banc de Sang i TeixitsVall d'Hebron Research Institute (VHIR)CompletedRelapsing-Remitting Multiple Sclerosis | Secondary Progressive Multiple SclerosisSpain
-
BiogenElan PharmaceuticalsCompletedRelapsing-Remitting Multiple Sclerosis | Secondary Progressive Multiple SclerosisUnited States
-
Brigham and Women's HospitalMassachusetts General HospitalRecruitingMultiple Sclerosis | Relapsing Multiple Sclerosis | Primary Progressive Multiple Sclerosis | Secondary Progressive Multiple SclerosisUnited States
Clinical Trials on Interferon-beta-1a FBS-free/HSA-free
-
Centre Hospitalier Universitaire VaudoisBioPartners GmbHCompletedMultiple Sclerosis, Relapsing-Remitting
-
BiogenCompletedMultiple SclerosisUnited States
-
BiogenCompletedRelapsing Remitting Multiple SclerosisPortugal
-
BiocadCompletedMultiple SclerosisRussian Federation
-
CinnagenCompletedRelapsing Remitting Multiple Sclerosis (RRMS)Iran, Islamic Republic of
-
BiogenWithdrawnRelapsing Multiple Sclerosis
-
BiogenCompletedRelapsing-Remitting Multiple Sclerosis (RRMS)Italy
-
EMD SeronoMerck Serono International SACompletedUlcerative ColitisSweden, Germany, Netherlands, Israel, Singapore, Switzerland, United Kingdom
-
Merck KGaA, Darmstadt, GermanyCompletedRelapsing-Remitting Multiple SclerosisGermany, Estonia, Latvia, Lithuania, Finland, Austria, Denmark, Netherlands, Portugal, Switzerland, Norway, Italy