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

NCT01142466 | Completed Phase 4 Results

• 1 other identifier: IMP 25874
• Study Type: interventional
• Target: 30
• Locations: 0 countries
• Sites: N/A

Brief 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.

Conditions

Multiple Sclerosis, Relapsing-Remitting

Keywords

Multiple sclerosis; Expanded Disability Status Scale; Multiple Sclerosis, Relapsing-Remitting; Rebif; Beta-1, interferon

Outcome Measures

Primary Outcomes (1)

• Time From Baseline to First Multiple Sclerosis Relapse (in Weeks)

  A qualifying relapse was defined as a new or worsening neurological symptom, in the absence of fever, lasting for \>= 48 hours, and accompanied by an objective change in the relevant (i.e. symptomatic) Kurtzke Functional Systems (KFS).

  Baseline through Week 96

Secondary Outcomes (6)

• Number of Relapse-free Participants

  Baseline through Week 96

• Absolute Changes in the Number of T1 Lesions From Baseline to Week 24, 48, 72 and 96

  Baseline to Week 24, 48, 72, and 96

• Absolute Changes in the Number of T1-Gadolinium (T1-Gd) Lesions From Baseline to Week 24, 48, 72 and 96

  Baseline to Week 24, 48, 72, and 96

• Absolute Changes in the Number of T2 Lesions From Baseline to Week 24, 48, 72 and 96

  Baseline to Week 24, 48, 72, and 96

• Mean Changes in Expanded Disability Status Scale (EDSS) Score From Baseline to Week 12, 24, 36, 48, 60, 72, 84, and 96

  Baseline to Week 12, 24, 36, 48, 60, 72, 84, and 96

Study Arms (2)

Rebif (3x44 mcg) Group

EXPERIMENTAL

Drug: Interferon beta-1a (Rebif)

No treatment Group

NO INTERVENTION

Interventions

Interferon beta-1a (Rebif) DRUG

The dosage of IFN-beta-1a , following initial dose titration, was 44 mcg injected subcutaneously (s.c.) tiw. An auto-injector device, Rebiject, was available as an optional aid for the administration of IFN-beta-1a . IFN-beta-1a was administered, if possible, at the same time (preferably in the late afternoon or evening) on the same three days at least 48 hours apart each week.

Also known as: Rebif

Rebif (3x44 mcg) Group

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Merck KGaA, Darmstadt, Germany: lead
• Gesellschaft für Therapieforschung mbH: collaborator

MeSH Terms

Conditions

Multiple Sclerosis, Relapsing-Remitting; Multiple Sclerosis

Interventions

Interferon beta-1a

Condition Hierarchy (Ancestors)

Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Interferon-beta; Interferon Type I; Interferons; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors

Results Point of Contact

• Title: Medical Responsible
• Organization: Merck Serono GmbH, Germany, an affiliate of Merck KGaA, Darmstadt, Germany

service@merckgroup.com

+49 6151 72 5200

Study Officials

• Sigbert Jahn, PD Dr. med

  Merck Serono GmbH, Germany

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 10, 2010
• First Posted: June 11, 2010
• Study Start: December 1, 2005
• Primary Completion: December 1, 2009
• Study Completion: January 1, 2010
• Last Updated: February 27, 2014
• Results First Posted: June 10, 2011

Record last verified: 2014-01