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CompletedNCT00110396RNFUpdated Jul 15, 2015Results posted

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

A Phase 3 interventional study of Interferon-beta-1a FBS-free/HSA-free in Multiple Sclerosis, sponsored by EMD Serono. Completed at 1 site in United States. Open to participants aged 18 Years to 60 Years. Per ClinicalTrials.gov, last updated 2015-07-15.

Sponsored by EMD Serono · Phase 3, Interventional, and Treatment

Phase
Phase 3
Study type
Interventional
Enrollment
260
Allocation
Non-randomized
Ages
18 Years to 60 Years
Sex
All
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Study 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.

Read the 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.

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Conditions studied

  • Multiple Sclerosis

Keywords

  • Multiple Sclerosis
  • Relapsing forms of multiple sclerosis
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In context

Multiple Sclerosis

3,460 studies on the registry are indexed under Multiple Sclerosis; 661 are open to participants now.

This study's enrollment of 260 is above the median of 50 across 2,342 interventional studies indexed under Multiple Sclerosis.

Browse Multiple Sclerosis studies →

Lead sponsor

EMD Serono is the lead sponsor of 88 studies on the registry; none are open to participants now.

Counted across the registry records on this site, refreshed daily.

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Who can participate

Ages eligible
18 Years to 60 Years
Sexes eligible
All
Accepts healthy volunteers
No

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

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.
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Study design

Phase
Phase 3
Primary purpose
Treatment
Allocation
Non-randomized
Intervention model
Single group
Masking
None (open label)
Enrollment
260 participants (actual)

Study arms

  • Experimental
    Rebif New Formulation Cohort

    Biological: Interferon-beta-1a FBS-free/HSA-free

Interventions

  • BiologicalInterferon-beta-1a FBS-free/HSA-free

    Pre-filled syringes 44mcg/injected subcutaneous 3x per week. Total study period is 96 weeks.

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What researchers measure

Primary outcomes

  1. 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.

    Time frame: 96 weeks

Secondary outcomes

  1. 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.

    Time frame: 96 weeks

  2. Number of Participants With Binding Antibodies (BAb) at Week 96

    Presence of BAbs. BAbs were measured by ELISA (Enzyme-linked immunosorbent assay).

    Time frame: 96 weeks

07

Results

Posted Jul 9, 2010

Participant flow

Participants were enrolled from 25 Jan 2005 and attended the last visit on 16 April 2007. Two hundred and eighty two participants were screened for enrollment and 260 were enrolled.

Participant flow — Overall Study
MilestoneRebif New Formulation (RNF) Cohort
Started260
Completed224
Not completed36
Withdrew: Adverse event15
Withdrew: Lost to follow-up1
Withdrew: Administration of plasmapheresis1
Withdrew: Initiated mitoxantrone therapy1
Withdrew: Lack of efficacy1
Withdrew: Decided not to continue treatment1
Withdrew: Patient non-compliance1
Withdrew: Patient refused to continue1
Withdrew: Patient refused to participate1
Withdrew: Patient will1
Withdrew: Patient's decision1
Withdrew: Participation in ms vaccine study1
Withdrew: Pregnancy1
Withdrew: Pregnancy (protocol violation)2
Withdrew: Protocol violation2
Withdrew: Patient refused to come back1
Withdrew: The patient has refused2
Withdrew: The patient has refused to visit site1
Withdrew: Patient is to be administered copaxone1

Outcome measures

PrimaryNumber 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.

Time frame:
96 weeks
Reported as:
Number · participants
Number of Participants Who Were Neutralising Antibody (NAb) Positive at the Week 96 Visit.
participantsRebif New Formulation (RNF) Cohort
Number of Participants Who Were Neutralising Antibody (NAb) Positive at the Week 96 Visit.45
SecondaryNumber 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.

Time frame:
96 weeks
Reported as:
Number · participants
Number of Participants Who Were Neutralising Antibody (NAb) Positive at Anytime During the Study
participantsRebif New Formulation (RNF) Cohort
Number of Participants Who Were Neutralising Antibody (NAb) Positive at Anytime During the Study49
SecondaryNumber of Participants With Binding Antibodies (BAb) at Week 96

Presence of BAbs. BAbs were measured by ELISA (Enzyme-linked immunosorbent assay).

Time frame:
96 weeks
Reported as:
Number · Participants
Number of Participants With Binding Antibodies (BAb) at Week 96
ParticipantsRebif New Formulation (RNF) Cohort
Number of Participants With Binding Antibodies (BAb) at Week 9674

Adverse events

Collected over Adverse event reporting began at signature of informed consent and continued until 4 weeks after the last administration of trial medication.. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Rebif New Formulation (RNF) Cohort—15/260 (5.8%)247/260 (95%)
Most frequent serious events
Showing 10 of 18
Most frequent serious events
EventRebif New Formulation (RNF) Cohort
DepressionPsychiatric disorders3/260
Drug toxicityInjury, poisoning and procedural complications1/260
Humerus fractureInjury, poisoning and procedural complications1/260
Joint dislocationInjury, poisoning and procedural complications1/260
Limb injuryInjury, poisoning and procedural complications1/260
Near drowningInjury, poisoning and procedural complications1/260
HypomaniaPsychiatric disorders1/260
EndometriosisReproductive system and breast disorders1/260
Menstrual disorderReproductive system and breast disorders1/260
Ovarian cyst rupturedReproductive system and breast disorders1/260
Most frequent other events
Showing 10 of 24
Most frequent other events
EventRebif New Formulation (RNF) Cohort
Influenza like illnessGeneral disorders176/260
HeadacheNervous system disorders98/260
Injection site erythemaGeneral disorders63/260
NauseaGastrointestinal disorders26/260
Back painMusculoskeletal and connective tissue disorders26/260
Injection site haemorrhageGeneral disorders25/260
FatigueGeneral disorders24/260
Upper respiratory tract infectionInfections and infestations23/260
ArthralgiaMusculoskeletal and connective tissue disorders21/260
Pain in extremityMusculoskeletal and connective tissue disorders20/260

Baseline characteristics

Age, Categorical
Age, Categorical(Participants)Rebif New Formulation (RNF) Cohort
<=18 years0
Between 18 and 65 years260
>=65 years0
Age, Continuous
Age, Continuous(years)Rebif New Formulation (RNF) Cohort
Mean34.9 ± 9.5
Sex: Female, Male
Sex: Female, Male(Participants)Rebif New Formulation (RNF) Cohort
Female186
Male74
Region of Enrollment
Region of Enrollment(participants)Rebif New Formulation (RNF) Cohort
Argentina14
Australia10
Canada4
Denmark4
Ireland4
Israel4
Lithuania20
Russian Federation134
Spain13
Sweden5
United Kingdom23
United States25
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Study locations

1 site
  • Local US Medical Information
    Rockland, Massachusetts 02370, United States
09

References and documents

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. PubMed 17692727 ↗
  • 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. PubMed 18755819 ↗
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Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Jul 15, 2015, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
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Registry details

Key details

Study ID
NCT00110396
Lead sponsor
EMD Serono
Collaborators
Pfizer
First posted
May 9, 2005
Start date
Jan 2005
Primary completion
Apr 2007
Completion
Apr 2007
Results posted
Jul 9, 2010
Last update
Jul 15, 2015

Study contacts

Bettina Stubinski, MD
study director · Merck Serono SA - Geneva
View the source record on ClinicalTrials.gov ↗

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