Relapsing Remitting Multiple Sclerosis (RRMS)Phase 3REFORMSNCT00428584
RNF and Betaseron® Tolerability Study
A Phase 3 study testing New Formulation of rebif - human interferon beta-1a and Interferon beta -1b in people with Relapsing Remitting Multiple Sclerosis (RRMS), run by EMD Serono at 1 site in United States.
Trial summary
To evaluate the tolerability of a new formulation of rebif and Betaseron in subjects with relapsing-remitting multiple sclerosis (RRMS) by comparing the mean change in injection site pain scores from pre-injection to 30 minutes post therapy administration. Read more about this study
- Who is it for?
- Ages 18 to 60 years
- Conditions the study is for
- Relapsing Remitting Multiple Sclerosis (RRMS)
- What is being tested?
- New Formulation of rebif - human interferon beta-1a and Interferon beta -1b
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 129 participants
- Where
- 1 siteUnited States
- Study dates
- Dec 2006to Sep 2009
- 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
- Subject with diagnosis of RRMS according to McDonald criteria or Poser
- Subject is between 18 and 60 years old inclusive
- Subject is willing to follow study procedures
- Subject has given written informed consent
- Female subjects 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.
Who cannot join
- Subject has Clinically Isolated Syndrome (CIS), Primary Progressive MS, or Secondary Progressive MS without superimposed relapses.
- Subject has had any prior interferon beta therapy (either beta-1b or beta-1a) prior to study Day 1.
- Subject received any other approved disease modifying therapy for MS (glatiramer acetate) or any cytokine or anti-cytokine therapy within the 3 months prior to Study Day 1.
- Subject received immunomodulatory or immunosuppressive therapy (including but not limited to cyclophosphamide, cyclosporin, methotrexate, azathioprine, linomide, mitoxantrone, teriflunomide, natalizumab, laquinimod, Campath and cladribine) within the 12 months prior to Study Day 1.
- Subject had prior use of Cladribine or has previously received total lymphoid irradiation.
- Subject has known allergy to natural or recombinant interferon or any other component of formulation excipient(s) of Rebif® or Betaseron®: Mannitol, Poloxamer 188, Methionine, Benzyl alcohol or Albumin (human).
Show all 18Show fewer
- Use of any other injectable medications on a regular basis during the week prior to the screening period or during the screening or treatment periods. Receiving a single injection for treatment or prophylaxis of a condition unrelated to the subject's multiple sclerosis or the subject's Rebif® or Betaseron® therapy (e.g. receiving a influenza or pneumococcus vaccination) is acceptable.
- History of any chronic pain syndrome.
- Subject has any other disease apart from MS that could better explain the subjects signs and symptoms.
- Subject has complete transverse myelitis or bilateral optic neuritis.
- Subjects who used any investigational drug or experimental procedure within 12 weeks prior to visit 1.
- Subject 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.
- Subject has inadequate bone marrow reserve, defined as a white blood cell count less than 0.5 x lower limit of normal.
- Subject suffers from current autoimmune disease (other than RRMS).
- Subject 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
- Subject is pregnant or attempting to conceive
- Visual or physical impairment that precludes completion of diaries and questionnaires.
- Subject received oral or systemic corticosteroids or ACTH within 30 days of visit 1.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Randomized, Multicenter, Two Arm, Open Label, Twelve Week Phase IIIb Study to Evaluate the Tolerability of Rebif (New Formulation) (IFN Beta-1a) and Betaseron (IFN Beta-1b) in IFN-naive Subjects With Relapsing Remitting Multiple Sclerosis (RRMS) Followed by a Single Arm, Eighty-two Week Minimum, Rebif (New Formulation) Only Safety Extension
To evaluate the tolerability of a new formulation of rebif and Betaseron in subjects with relapsing-remitting multiple sclerosis (RRMS) by comparing the mean change in injection site pain scores from pre-injection to 30 minutes post therapy administration.
- Being tested
- New Formulation of rebif - human interferon beta-1a, Interferon beta -1b
- Medical subject headings
- Multiple Sclerosis, Relapsing-Remitting
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
New Formulation of rebif - human interferon beta-1aDrug
New Formulation of rebif- 44 mcg, SC (sub-cutaneous) thrice weekly (tiw) injection.
Interferon beta -1bDrug
Betaseron - 250 mcg, SC (sub-cutaneous) every other day injection.
| Study group | Role | What they receive |
|---|---|---|
| 1 | Experimental | interferon beta-1a Receives: Drug: New Formulation of rebif - human interferon beta-1a |
| 2 | Active comparator | interferon beta-1b Receives: Drug: Interferon beta -1b |
What is being measured
The primary outcome is the main question the study is designed to answer.
Visual Analog Scale (VAS) of Patient Reported Pain: Change in Mean VAS for the 21 Full-dose Injections at Pre-injection and 30 Minutes Post-injection Timepoints
Subject reported perception of pain on the VAS where the slash drawn by the patient represents pain of increasing intensity from 0 (no pain) to 100 (worse possible pain), measured in millimeters. Mean VAS of 21 injections for each patient at pre-injection compared to mean VAS of 21 injections for each patient 30 minutes post-injection
Measured: From pre-injection to 30 minutes post injection of the VAS pain scores across the first 21 injections of full dose therapy of a new formulation of rebif and Betaseron
Secondary outcomes (4)
Change in Mean VAS for the 21 Full-dose Injections at Pre-injection and Immediately After Injection Timepoints
A visual analog scale (VAS) ranging from 0 to 100 mm on which subjects rate pain from no pain (0 mm) to worst possible pain (100 mm) was used. Mean VAS of 21 injections for each patient at pre-injection compared to mean VAS of 21 injections for each patient immediately after injection.
Measured: Pre-Injection to Immediately after Injection
Change in Mean VAS for the 21 Full-dose Injections at Pre-injection and 10 Minutes Post-injection Timepoints
A visual analog scale (VAS) ranging from 0 to 100 mm on which subjects rate pain from no pain (0 mm) to worst possible pain (100 mm) was used. Mean VAS of 21 injections for each patient at pre-injection compared to mean VAS of 21 injections for each patient 10 minutes post injection.
Measured: Pre-injection to 10 minutes post-injection
Number of Pain Free Patients at 30 Minutes Post-injection
A visual analog scale (VAS) ranging from 0 to 100 mm on which subjects rate pain from no pain (0 mm) to worst possible pain (100 mm) was used.
Pain-free was defined as a VAS score of 0 for all 21 full-dose injections for the Intent-to-Treat (ITT) population.
Measured: 30 minutes post injection
Diameter of Injection Site Redness
Blinded assessment of mean change in diameter of redness (in mm) at an injection site following an injection
Measured: 1-72 hours post injection over the first 12 weeks including the titration period
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Jan 2007 (estimated)
- Study startDec 2006
- Primary completionNov 2007
- Study completionSep 2009
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 (1)Papers the sponsor has linked to this study.
- Other trials for Relapsing Remitting Multiple Sclerosis (RRMS)Studies 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
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 129 participants (actual)
Sponsor and investigators
- Lead sponsor
- EMD Serono
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Pfizer
- Investigators
- Fernando Dangond, MD, Study director, EMD Serono
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00428584
- Sponsor's protocol ID
- 27133
- Acronym
- REFORMS
- Status last verified
- Aug 2013
- First submitted
- 29 Jan 2007
- Last updated
- 7 Aug 2013
- Results posted
- Yes, on ClinicalTrials.gov
Publications
Singer B, Bandari D, Cascione M, LaGanke C, Huddlestone J, Bennett R, Dangond F; REFORMS Study Group. Comparative injection-site pain and tolerability of subcutaneous serum-free formulation of interferonbeta-1a versus subcutaneous interferonbeta-1b: results of the randomized, multicenter, Phase IIIb REFORMS study. BMC Neurol. 2012 Dec 6;12:154. doi: 10.1186/1471-2377-12-154.
PubMed 23216674
Study at a glance
From the registry record, last updated by the sponsor on 7 Aug 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Multicenter, Two Arm, Open Label, Twelve Week Phase IIIb Study to Evaluate the Tolerability of Rebif (New Formulation) (IFN Beta-1a) and Betaseron (IFN Beta-1b) in IFN-naive Subjects With Relapsing Remitting Multiple Sclerosis (RRMS) Followed by a Single Arm, Eighty-two Week Minimum, Rebif (New Formulation) Only Safety Extension
- ClinicalTrials.gov ID
- NCT00428584
- Acronym / sponsor ID
- REFORMS / 27133
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 129 participants (actual)
- Lead sponsor
- EMD SeronoIndustry (pharma, biotech, devices)
- Collaborators
- Pfizer
- Study start
- Dec 2006
- Primary completion
- Nov 2007 (actual)
- Study completion
- Sep 2009 (actual)
- First posted
- 30 Jan 2007 (estimated)
- Results
- Posted 4 Mar 2010
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
To evaluate the tolerability of a new formulation of rebif and Betaseron in subjects with relapsing-remitting multiple sclerosis (RRMS) by comparing the mean change in injection site pain scores from pre-injection to 30 minutes post therapy administration.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 1 | Experimental | Drug: New Formulation of rebif - human interferon beta-1ainterferon beta-1a |
| 2 | Active comparator | Drug: Interferon beta -1binterferon beta-1b |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (7 listed)
- Subject with diagnosis of RRMS according to McDonald criteria or Poser
- Subject is between 18 and 60 years old inclusive
- Subject is willing to follow study procedures
- Subject has given written informed consent
- Female subjects must be neither pregnant nor breast-feeding and must lack childbearing potential, as defined by either:
Key exclusion criteria (18 listed)
- Subject has Clinically Isolated Syndrome (CIS), Primary Progressive MS, or Secondary Progressive MS without superimposed relapses.
- Subject has had any prior interferon beta therapy (either beta-1b or beta-1a) prior to study Day 1.
- Subject received any other approved disease modifying therapy for MS (glatiramer acetate) or any cytokine or anti-cytokine therapy within the 3 months prior to Study Day 1.
- Subject received immunomodulatory or immunosuppressive therapy (including but not limited to cyclophosphamide, cyclosporin, methotrexate, azathioprine, linomide, mitoxantrone, teriflunomide, natalizumab, laquinimod, Campath and cladribine) within the 12 months prior to Study Day 1.
- Subject 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 |
|---|---|---|
| New Formulation of rebif - human interferon beta-1aNew Formulation of rebif- 44 mcg, SC (sub-cutaneous) thrice weekly (tiw) injection. | Drug | 1 |
| Interferon beta -1bBetaseron - 250 mcg, SC (sub-cutaneous) every other day injection. | Drug | 2 |
Primary outcome
Visual Analog Scale (VAS) of Patient Reported Pain: Change in Mean VAS for the 21 Full-dose Injections at Pre-injection and 30 Minutes Post-injection Timepoints
Time frame: From pre-injection to 30 minutes post injection of the VAS pain scores across the first 21 injections of full dose therapy of a new formulation of rebif and Betaseron
Subject reported perception of pain on the VAS where the slash drawn by the patient represents pain of increasing intensity from 0 (no pain) to 100 (worse possible pain), measured in millimeters. Mean VAS of 21 injections for each patient at pre-injection compared to mean VAS of 21 injections for each patient 30 minutes post-injection
4 secondary outcomes
Change in Mean VAS for the 21 Full-dose Injections at Pre-injection and Immediately After Injection Timepoints
Time frame: Pre-Injection to Immediately after Injection
Change in Mean VAS for the 21 Full-dose Injections at Pre-injection and 10 Minutes Post-injection Timepoints
Time frame: Pre-injection to 10 minutes post-injection
Number of Pain Free Patients at 30 Minutes Post-injection
Time frame: 30 minutes post injection
Diameter of Injection Site Redness
Time frame: 1-72 hours post injection over the first 12 weeks including the titration period
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Aug 2013.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 23216674Singer B, Bandari D, Cascione M, LaGanke C, Huddlestone J, Bennett R, Dangond F; REFORMS Study Group. Comparative injection-site pain and tolerability of subcutaneous serum-free formulation of interferonbeta-1a versus subcutaneous interferonbeta-1b: results of the randomized, multicenter, Phase IIIb REFORMS study. BMC Neurol. 2012 Dec 6;12:154. doi: 10.1186/1471-2377-12-154.
- 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.
Fernando Dangond, MD study director
EMD Serono
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 New Formulation of rebif - human interferon beta-1a and Interferon beta -1b in people with Relapsing Remitting Multiple Sclerosis (RRMS), 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 7 inclusion and 18 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 7 Aug 2013. 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 4 Mar 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?
Visual Analog Scale (VAS) of Patient Reported Pain: Change in Mean VAS for the 21 Full-dose Injections at Pre-injection and 30 Minutes Post-injection Timepoints (time frame: From pre-injection to 30 minutes post injection of the VAS pain scores across the first 21 injections of full dose therapy of a new formulation of rebif and Betaseron). 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 NCT00428584, which also lists 1 linked publication.
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 7 Aug 2013.