Multiple SclerosisPhase 3RNFNCT00110396
Rebif New Formulation (RNF) in Relapsing Forms of Multiple Sclerosis
A Phase 3 study testing Interferon-beta-1a FBS-free/HSA-free in people with Multiple Sclerosis, run by EMD Serono at 1 site in United States.
Trial 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 more about this study
- Who is it for?
- Ages 18 to 60 years
- Conditions the study is for
- Multiple Sclerosis
- What is being tested?
- Interferon-beta-1a FBS-free/HSA-free
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 260 participants
- Where
- 1 siteUnited States
- Study dates
- Jan 2005to Apr 2007
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 60 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- 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
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- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
Local US Medical Information
Rockland, Massachusetts, 02370
About this study
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
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.
- Conditions
- Multiple Sclerosis
- Being tested
- Interferon-beta-1a FBS-free/HSA-free
- Keywords
- Multiple Sclerosis, Relapsing forms of multiple sclerosis
- Medical subject headings
- Multiple Sclerosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Interferon-beta-1a FBS-free/HSA-freeBiological
Pre-filled syringes 44mcg/injected subcutaneous 3x per week. Total study period is 96 weeks.
| Study group | Role | What they receive |
|---|---|---|
| Rebif New Formulation Cohort | Experimental | Not described Receives: Biological: Interferon-beta-1a FBS-free/HSA-free |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 96 weeks
Secondary outcomes (2)
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.
Measured: 96 weeks
Number of Participants With Binding Antibodies (BAb) at Week 96
Presence of BAbs. BAbs were measured by ELISA (Enzyme-linked immunosorbent assay).
Measured: 96 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 May 2005 (estimated)
- Study startJan 2005
- Primary completionApr 2007
- Study completionApr 2007
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Multiple SclerosisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 260 participants (actual)
Sponsor and investigators
- Lead sponsor
- EMD Serono
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Pfizer
- Investigators
- Bettina Stubinski, MD, Study director, Merck Serono SA - Geneva
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00110396
- Sponsor's protocol ID
- 25632
- Acronym
- RNF
- Status last verified
- Jun 2015
- First submitted
- 6 May 2005
- Last updated
- 15 Jul 2015
- Results posted
- Yes, on ClinicalTrials.gov
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 17692727Giovannoni 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
Study at a glance
From the registry record, last updated by the sponsor on 15 Jul 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT00110396
- Acronym / sponsor ID
- RNF / 25632
- Conditions
- Multiple Sclerosis
- Keywords
- Multiple Sclerosis, Relapsing forms of multiple sclerosis
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 260 participants (actual)
- Lead sponsor
- EMD SeronoIndustry (pharma, biotech, devices)
- Collaborators
- Pfizer
- Study start
- Jan 2005
- Primary completion
- Apr 2007 (actual)
- Study completion
- Apr 2007 (actual)
- First posted
- 9 May 2005 (estimated)
- Results
- Posted 9 Jul 2010
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Rebif New Formulation Cohort | Experimental | Biological: Interferon-beta-1a FBS-free/HSA-free |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (10 listed)
- 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
Key exclusion criteria (15 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Interferon-beta-1a FBS-free/HSA-freePre-filled syringes 44mcg/injected subcutaneous 3x per week. Total study period is 96 weeks. | Biological | Rebif New Formulation Cohort |
Primary outcome
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.
2 secondary outcomes
Number of Participants Who Were Neutralising Antibody (NAb) Positive at Anytime During the Study
Time frame: 96 weeks
Number of Participants With Binding Antibodies (BAb) at Week 96
Time frame: 96 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Jul 2015.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 17692727Giovannoni 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 publication: PubMed 18755819Giovannoni 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.
- Full FDA approved prescribing information can be found hereLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Bettina Stubinski, MD study director
Merck Serono SA - Geneva
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Interferon-beta-1a FBS-free/HSA-free in people with Multiple Sclerosis, run by EMD Serono at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 15 Jul 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 9 Jul 2010). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants Who Were Neutralising Antibody (NAb) Positive at the Week 96 Visit. (time frame: 96 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00110396, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Jul 2015; AzTrials last refreshed its copy on 1 Nov 2026.