Phase 4 N=30 Randomized Treatment

A Phase IV 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

Multiple Sclerosis, Relapsing-Remitting

Bottom Line

View on ClinicalTrials.gov: NCT01142466 ↗

Enrolled (actual)

Serious AEs

20.0%

Results posted

Jun 2011

Primary outcome: Primary: Time From Baseline to First Multiple Sclerosis Relapse (in Weeks) — 35.5; 40.9 weeks — p=0.1384

Study Design & Population

Study type: Interventional
Phase: Phase 4
Interventions: Interferon beta-1a (Rebif) (Drug)
Age: Adult · 18+ yrs
Sex: All
Sponsor: Merck KGaA, Darmstadt, Germany
Primary completion: Dec 2009

Outcome Measures

Outcome	Result	p-value
PRIMARY Time From Baseline to First Multiple Sclerosis Relapse (in Weeks)	35.5; 40.9	0.1384
SECONDARY Number of Relapse-free Participants	10; 7	0.2635
SECONDARY Absolute Changes in the Number of T1 Lesions From Baseline to Week 24, 48, 72 and 96	-0.5; -0.9; -0.8; 1.5; -0.8; -3.6	—
SECONDARY Absolute Changes in the Number of T1-Gadolinium (T1-Gd) Lesions From Baseline to Week 24, 48, 72 and 96	—	—
SECONDARY Absolute Changes in the Number of T2 Lesions From Baseline to Week 24, 48, 72 and 96	-1.2; 1.0; 0.2; 3.2; -1.8; 3.1	—
SECONDARY Mean Changes in Expanded Disability Status Scale (EDSS) Score From Baseline to Week 12, 24, 36, 48, 60, 72, 84, and 96	-0.1; -0.1; 0.3; 0.1; 0.5; -0.2	—
SECONDARY Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE)	15; 14; 5; 1	—

Summary

In the course of therapy escalation, the multiple sclerosis (MS) subjects with high activity of disease receive mainly mitoxantrone. The duration of therapy is limited because of a cumulative dose for life (140 mg/m^2 body surface area). In practice lower doses of mitoxantrone (60-120 mg/m^2 body surface area) are being used. The specific reason for this limited total dose are potential cardiotoxic side effects of mitoxantrone. Once this cumulative dose of mitoxantrone is reached and the subject becomes stable, there is the question for subsequent therapy. A possibility at this time, is the so-called "de-escalation", therefore reducing the subject back to immunomodulating basic treatment. The target of this open-label, randomised, multicentric, comparative, parallel-group study was to inquire systematically into the use and course of basic therapy with Rebif 44 mcg thrice weekly (tiw) for a larger number of subjects.

Eligibility Criteria

Inclusion Criteria

Subject who had given written informed consent.
Subjects with definite RRMS or SPMS with relapses
Subjects with EDSS 1-6
Subjects aged between 18-60 years
Subjects who were escalated to mitoxantrone due to high relapse activity or MRI activity (not due to EDSS progression exclusively)
Subjects who may not have a confirmed 1 point EDSS progression (0.5 points for EDSS >5.5) within the last 9 months
Subjects free of relapses over the last 6 months
Subjects with last mitoxantrone treatment between 1 and 6 months prior to screening
Subjects treated with mitoxantrone for minimum 9 months and maximum 36 months, total cumulative dose being 40-120 mg/m^2
Female subjects who 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 who has received any cytokine or anti-cytokine therapy within the 3 months prior to study Day 1
Subject who has been escalated to mitoxantrone due to EDSS progression
Subject with an ongoing MS relapse
Subject with PPMS
Subject with SPMS without superimposed relapses
Subject who has received immunomodulatory treatment other than IFN-beta or glatiramer acetate before mitoxantrone
Subject who has previously received total lymphoid irradiation
Subject who has received oral or systemic corticosteroids or adrenocorticotrophic hormone ACTH within 30 days of study Day 1
Subject who has received intravenous immunoglobulins or underwent plasmapheresis within the 6 months prior to study day 1
Subject who has received immunomodulatory or immunosuppressive therapy (including but not limited to cyclophosphamide, cyclosporin, methotrexate, azathioprine, linomide, teriflunomide, natalizumab, laquinimod, Campath) within the 12 months prior to study Day 1
Subject who requires chronic or monthly pulse corticosteroids during the study
Subject who has received any investigational drug or experimental procedure within 12 month of study Day 1
Subject who 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 who has inadequate bone marrow reserve, defined as a white blood cell count less than 0.5 times the lower limit of normal
Subject who suffers from current autoimmune disease
Subject with known allergy to IFN or the excipient(s)
Subject who 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 treated with drugs other than IFN-beta or glatiramer acetate within 2 years before mitoxantrone
Subject with known cardiac or other systemic diseases
Subjects who are pregnant.

View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT01142466). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.