Study of Rebif® Compared With no Treatment in the Therapy of Relapsing Multiple Sclerosis After Mitoxantrone

Condition(s) targeted: Multiple Sclerosis, Relapsing-Remitting

Intervention: Rebif® (Drug); No Intervention (Other)

Phase: Phase 4

Status: Active, not recruiting

Sponsored by: EMD Serono

Official(s) and/or principal investigator(s):
Jahn Sigbert, M.D., Study Director, Affiliation: Merck Serono International S.A., an affiliate of Merck KGaA, Darmstadt, Germany

This will be an open-label, randomized, multicenter, comparative, parallel-group study with a neurologist blinded to treatment for performing neurologic exams and a neuroradiologist blinded to treatment for assessing central magnetic resonance imaging (MRI) scans. Subjects will be treated for two years. This study in patients with relapsing remitting multiple sclerosis (RRMS) who have completed treatment with mitoxantrone between >= 1 and <=6 months prior to randomization months prior to randomization will compare the therapeutic effect of subsequent high dose, high frequency interferon (IFN) beta 1a therapy with patients who receive no treatment following discontinuation of mitoxantrone. Rebif® will be supplied as a sterile, preservative-free solution pre-filled syringe of 8,8 mcg and 22 mcg for initial titration or as a 44 mcg pre-filled syringe. The primary objective of the study is to compare the time to first relapse in subjects treated with Rebif® 44 mcg three times per week with that of subjects not treated during 96 weeks after previous treatment with mitoxantrone.

The main secondary objective of the study is to compare the mean number of T2 active lesions, defined as new or enlarging T2 lesions, per subject per scan during 96 weeks of treatment with Rebif® 44 mcg three times per week with subjects not treated.

Safety and efficacy data will be obtained through repeated neurological examinations, MRI scans, routine clinical follow-up, routine haematology, clinical chemistry, urinalysis, determination of titre of antibodies to study drug, and monitoring of adverse events.

Official title: Phase IV, Multicenter, Open Label, Randomized Study of Rebif® 44mcg Administered Three Times Per Week by Subcutaneous Injection Compared With no Treatment in the Therapy of Relapsing Multiple Sclerosis After Mitoxantrone

Study design: Treatment, Randomized, Open Label, Uncontrolled, Parallel Assignment, Efficacy Study

Primary outcome: Time to first relapse.

Secondary outcome: Change in EDSS score from baseline to weeks 12, 24, 36, 48, 60, 72, 84 and 96, changes in MRI criteria (T1, T1-Gd, T2) from baseline to weeks 24, 48, 72 and 96 and Change in MSFC score from baseline to weeks 12, 24, 36, 48, 60, 72, 84 and 96

Minimum age: 18 Years. Maximum age: 60 Years. Gender(s): Both.

Criteria:

Inclusion Criteria:

- Subject has given written informed consent.

- Definite RRMS or secondary progressive multiple sclerosis (SPMS) with relapses

- Expanded Disability Status Scale (EDSS) 1-6

- Age 18-60 years

- Escalation to mitoxantrone due to relapse activity or MRI activity during last year

prior to mitoxantrone or EDSS progression combined with relapse activity or MRI activity during last year prior to mitoxantrone (not due to EDSS progression exclusively)

- Subject may not have a confirmed 1point EDSS progression (0. 5 points for EDSS > 5. 5)

within the last 9 months

- Subject should be free of relapses over the last 6 months.

- Last mitoxantrone treatment between >=1 and <=06 month

- Mitoxantrone for min. 9, max. 36 months, total cumulative dose 40-120 mg/m2 body

surface area in the last cycle

- 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. Confirmation that the subject is not pregnant must be established by a negative serum or urinary human chorionic gonadotropin (hCG) test within 7 days prior to start of study treatment. A pregnancy test is not required if the subject is post-menopausal or surgically sterile.

Exclusion Criteria:

- Subject received any cytokine or anti-cytokine therapy within the 3 months prior to

Study Day 1 (SD1, Week 0).

- Subject was escalated to mitoxantrone due to EDSS progression only (without any

relapse or MRI activity during the last year prior to mitoxantrone).

- Subject has primary progressive MS.

- Subject has secondary progressive MS without superimposed relapses.

- Subject received immunomodulatory treatment other than IFN-beta, glatirameracetat,

azatioprine, immunoglobulins, or no treatment before mitoxantrone.

- Subject has previously received total lymphoid irradiation.

- Subject received oral or systemic corticosteroids or adrenocorticotropic hormone

(ACTH) within 30 days of SD1 (Week 0).

- Subject received intravenous immunoglobulins or underwent plasmapheresis within the 6

months prior to SD1 (Week 0).

- Subject received immunomodulatory or immunosuppressive therapy (including but not

limited to cyclophosphamide, cyclosporin, methotrexate, azathioprine, linomide, teriflunomide, laquinimod, Campath) within the 12 months prior to SD1 (Week 0).

- Subject requires chronic or monthly pulse corticosteroids during the study.

- Subject received any investigational drug or experimental procedure within 12 months

of SD1 (Week 0) or is currently participating in another clinical trial.

- Subject has inadequate liver function, defined by a total bilirubin, aspartate

aminotransferase (AST) or alanine aminotransferase (ALT) or alkaline phosphatase greater than 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 times the lower limit of normal and platelet count <100x103/µl.

- Subject suffers from the following concurrent autoimmune diseases: SLE, ITP,

Rheumatoid arthritis, Crohn´s Disease, Diabetes mellitus.

- Subject has a known allergy to IFN or the excipient(s).

- Subject suffers from major medical or psychiatric illness (e. g. severe depression

and/or suicide risk) that in the opinion of the investigator creates undue risk to the subject or could affect compliance with the study protocol.

- Known clinically significant cardiac or other systemic diseases

- Pregnancy

- Previous treatment with natalizumab

- Subject suffers from epilepsy without adequate therapeutic control of attacks.

Merck Serono International S.A., an affiliate of Merck KGaA,, Darmstadt, Germany

Full FDA approved prescribing information can be found here

Starting date: October 2005
Ending date: November 2010
Last updated: January 16, 2008