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

This study has been completed.
Sponsor:
Collaborator:
Pfizer
Information provided by:
EMD Serono
ClinicalTrials.gov Identifier:
NCT00110396
First received: May 6, 2005
Last updated: August 2, 2013
Last verified: June 2010
  Purpose

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.


Condition Intervention Phase
Multiple Sclerosis
Biological: Interferon-beta-1a FBS-free/HSA-free
Phase 3

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by EMD Serono:

Primary Outcome Measures:
  • Number of Participants Who Were Neutralising Antibody (NAb) Positive at the Week 96 Visit. [ Time Frame: 96 weeks ] [ Designated as safety issue: No ]
    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 [ Time Frame: 96 weeks ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    Presence of BAbs. BAbs were measured by ELISA (Enzyme-linked immunosorbent assay).


Enrollment: 260
Study Start Date: January 2005
Study Completion Date: April 2007
Primary Completion Date: April 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Rebif New Formulation Cohort Biological: Interferon-beta-1a FBS-free/HSA-free
Pre-filled syringes 44mcg/injected subcutaneous 3x per week. Total study period is 96 weeks.

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

Ages Eligible for Study:   18 Years to 60 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00110396

Locations
United States, Massachusetts
Local US Medical Information
Rockland, Massachusetts, United States, 02370
Sponsors and Collaborators
EMD Serono
Pfizer
Investigators
Study Director: Bettina Stubinski, MD Merck Serono SA - Geneva
  More Information

Additional Information:
Publications:
Responsible Party: Susan Fischer, EMD Serono Inc
ClinicalTrials.gov Identifier: NCT00110396     History of Changes
Other Study ID Numbers: 25632
Study First Received: May 6, 2005
Results First Received: April 30, 2010
Last Updated: August 2, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by EMD Serono:
Multiple Sclerosis
Relapsing forms of multiple sclerosis

Additional relevant MeSH terms:
Multiple Sclerosis
Sclerosis
Demyelinating Autoimmune Diseases, CNS
Autoimmune Diseases of the Nervous System
Nervous System Diseases
Demyelinating Diseases
Autoimmune Diseases
Immune System Diseases
Pathologic Processes
Interferon-beta
Interferons
Interferon beta 1a
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Immunologic Factors
Physiological Effects of Drugs
Antineoplastic Agents
Adjuvants, Immunologic

ClinicalTrials.gov processed this record on July 22, 2014