RNF and Betaseron® Tolerability Study (REFORMS)

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.

Study Overview

• Status: Completed
• Conditions: Relapsing Remitting Multiple Sclerosis (RRMS)
• Intervention / Treatment: Drug: New Formulation of rebif - human interferon beta-1a; Drug: Interferon beta -1b

• Study Type: Interventional
• Enrollment (Actual): 129
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Rockland, Massachusetts, United States, 02370
      • EMD Serono Med Info

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Subject with diagnosis of RRMS according to McDonald criteria or Poser
2. Subject is between 18 and 60 years old inclusive
3. Subject is willing to follow study procedures
4. Subject has given written informed consent

5. 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.

Exclusion Criteria:

1. Subject has Clinically Isolated Syndrome (CIS), Primary Progressive MS, or Secondary Progressive MS without superimposed relapses.
2. Subject has had any prior interferon beta therapy (either beta-1b or beta-1a) prior to study Day 1.
3. 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.
4. 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.
5. Subject had prior use of Cladribine or has previously received total lymphoid irradiation.
6. 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).
7. 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.
8. History of any chronic pain syndrome.
9. Subject has any other disease apart from MS that could better explain the subjects signs and symptoms.
10. Subject has complete transverse myelitis or bilateral optic neuritis.
11. Subjects who used any investigational drug or experimental procedure within 12 weeks prior to visit 1.
12. 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.
13. Subject has inadequate bone marrow reserve, defined as a white blood cell count less than 0.5 x lower limit of normal.
14. Subject suffers from current autoimmune disease (other than RRMS).
15. 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
16. Subject is pregnant or attempting to conceive
17. Visual or physical impairment that precludes completion of diaries and questionnaires.
18. Subject received oral or systemic corticosteroids or ACTH within 30 days of visit 1.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1; interferon beta-1a	Drug: New Formulation of rebif - human interferon beta-1a; New Formulation of rebif- 44 mcg, SC (sub-cutaneous) thrice weekly (tiw) injection.
Active Comparator: 2; interferon beta-1b	Drug: Interferon beta -1b; Betaseron - 250 mcg, SC (sub-cutaneous) every other day injection.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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.	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.	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	1-72 hours post injection over the first 12 weeks including the titration period

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Secondary Outcome - Extension Phase: Change in Mean (mm) VAS for 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.	Pre-injection and immediately after injection
Secondary Outcome - Extension Phase: Change in Mean VAS at Pre-injection and 10 Minutes Post Injection		Pre-injection and 10 minutes post injection
Secondary Outcome - Extension Phase: Number of Pain Free Patients at 30 Minutes Post Injection		Pain free patients at 30 minutes post injection
Secondary Outcome - Extension Phase: Diameter in Injection Site Redness		1 to 72 hours post injection
Primary Outcome - Extension Phase: Visual Analog Scale (VAS) of Patients Reported Pain; Change in Mean VAS at Pre-injection and 30 Minutes Post Injection		Pre-injection and 30 minutes post injection

Collaborators and Investigators

• Sponsor: EMD Serono
• Collaborators: Pfizer

Publications and helpful links

General 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.

Helpful Links

• Full FDA approved prescribing information can be found here

Study record dates

Study Major Dates

• Study Start: December 1, 2006
• Primary Completion (Actual): November 1, 2007
• Study Completion (Actual): September 1, 2009

Study Registration Dates

• First Submitted: January 29, 2007
• First Submitted That Met QC Criteria: January 29, 2007
• First Posted (Estimate): January 30, 2007

Study Record Updates

• Last Update Posted (Estimate): August 7, 2013
• Last Update Submitted That Met QC Criteria: August 1, 2013
• Last Verified: August 1, 2013

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; Multiple Sclerosis, Relapsing-Remitting; 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: 27133