Clinical trial NCT00428584: RNF and Betaseron® Tolerability 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Relapsing Remitting Multiple Sclerosis (RRMS)
Lead sponsor: EMD Serono
Sponsor class: INDUSTRY
Collaborators: name: Pfizer
First posted: 2007-01-30
Enrollment: 129
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.


Eligibility criteria: 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.

Primary outcomes:
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
timeFrame: 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:
measure: Change in Mean VAS for the 21 Full-dose Injections at Pre-injection and Immediately After Injection Timepoints
timeFrame: Pre-Injection to Immediately after Injection
measure: Change in Mean VAS for the 21 Full-dose Injections at Pre-injection and 10 Minutes Post-injection Timepoints
timeFrame: Pre-injection to 10 minutes post-injection
measure: Number of Pain Free Patients at 30 Minutes Post-injection
timeFrame: 30 minutes post injection
measure: Diameter of Injection Site Redness
timeFrame: 1-72 hours post injection over the first 12 weeks including the titration period
Other outcomes:
measure: Secondary Outcome - Extension Phase: Change in Mean (mm) VAS for Pre-injection and Immediately After Injection Timepoints
timeFrame: Pre-injection and immediately after injection
measure: Secondary Outcome - Extension Phase: Change in Mean VAS at Pre-injection and 10 Minutes Post Injection
timeFrame: Pre-injection and 10 minutes post injection
measure: Secondary Outcome - Extension Phase: Number of Pain Free Patients at 30 Minutes Post Injection
timeFrame: Pain free patients at 30 minutes post injection
measure: Secondary Outcome - Extension Phase: Diameter in Injection Site Redness
timeFrame: 1 to 72 hours post injection
measure: Primary Outcome - Extension Phase: Visual Analog Scale (VAS) of Patients Reported Pain; Change in Mean VAS at Pre-injection and 30 Minutes Post Injection
timeFrame: Pre-injection and 30 minutes post injection
Locations:
city: Rockland
country: United States
facility: EMD Serono Med Info
state: Massachusetts
Study officials:
affiliation: EMD Serono
name: Fernando Dangond, MD
role: STUDY_DIRECTOR
References:
citation: 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.