Advertisement

Topics

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

2014-08-27 03:12:57 | BioPortfolio

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/m2 body surface area). In practice lower doses of mitoxantrone (60-120mg/m2 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.

Description

Multiple sclerosis is a chronic, inflammatory, demyelinating disease of the central nervous system (CNS) and is one of the most common causes of neurological disability in young adults. It is characterised by multi-focal recurrent attacks of neurological symptoms and signs with variable recovery. Eventually, the majority of subjects develop a progressive clinical course. The exact cause of MS is unknown, although an autoimmune process has been implicated. Genetic susceptibility plays a role in disease initiation but unidentified environmental factors may also be involved. Three clinical forms of MS are recognized: primary progressive multiple sclerosis (PPMS), secondary progressive multiple sclerosis (SPMS) and relapsing remitting multiple sclerosis (RRMS). Primary progressive subjects are characterised by slow and steady accumulation of neurological deficits from onset without superimposed attacks. Subjects with RRMS have exacerbations or relapses with subsequent variable recovery (remission). Secondary progressive multiple sclerosis is characterised by the steady accumulation of significant and persistent neurological deficit with or without superimposed relapses.

Rebif [recombinant interferon (IFN) beta-1a] has been tested in a series of studies in MS subjects at doses ranging from 22 mcg to 132 mcg weekly with a dose frequency ranging from weekly (qw) to tiw. Rebif has been found to be well tolerated in all clinical pharmacology studies, even at high doses (up to 66 mcg/m2). In later phase trials, Rebif has been tested across a broad range of doses, for varying duration, and in different stages of MS disease. Dose testing has ranged from 22 mcg to 132 mcg weekly with frequency of administration being qw to tiw.

OBJECTIVES

Primary objective:

- To asses if treatment with Rebif 44 mcg tiw compared with subjects not treated during 96 weeks can maintain or prolong clinical or magnetic resonance imaging (MRI) stability after previous treatment with mitoxantrone

Secondary objectives:

- 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

- To assess the safety and efficacy of Rebif 44 mcg

This was an open-label, randomised, multicentric, comparative, parallel-group study with a neurologist blinded to treatment for performing neurologic exams and a neuro-radiologist blinded to treatment for assessing central MRI scans. The study was divided into a screening phase (up to 28 days before the start of IFN-beta-1a treatment), a treatment phase of 96 weeks as well as a follow-up period of 4 weeks for subjects with ongoing serious adverse events (SAEs) at week 96. The study consisted of 2 groups to compare the therapeutic effect of high dose, high frequency IFN beta-1a therapy (Rebif 44 mcg) to subjects who will not be treated with Rebif 44 mcg. Subjects of both groups were previously treated with mitoxantrone in the < 3 months prior to study inclusion. Subjects assigned to no treatment were switched to Rebif 44 mcg x 3 after reaching the primary endpoint or defined stopping criteria. The treatment period of this study begun with the completion of all baseline evaluations and the initiation of study drug treatment on Study Day 1 (baseline visit) and continues through until completion of the treatment period at the Week 96 visit.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Conditions

Multiple Sclerosis, Relapsing-Remitting

Intervention

Interferon beta-1a (Rebif)

Status

Completed

Source

Merck KGaA

Results (where available)

View Results

Links

Published on BioPortfolio: 2014-08-27T03:12:57-0400

Clinical Trials [2344 Associated Clinical Trials listed on BioPortfolio]

Comparison of Alemtuzumab and Rebif® Efficacy in Multiple Sclerosis, Study One

The purpose of this study is to establish the efficacy and safety of alemtuzumab as a treatment for relapsing-remitting multiple sclerosis (MS), in comparison with Rebif® (interferon beta...

Rebif® Versus Copaxone® in the Treatment of Relapsing Remitting Multiple Sclerosis

The primary objective of the study is to assess the clinical efficacy of Rebif® 44 mcg three times per week compared with Copaxone® 20 mg daily in patients with relapsing Multiple Scle...

Comparison of Alemtuzumab and Rebif® Efficacy in Multiple Sclerosis, Study Two

The purpose of this study is to establish the efficacy and safety of two different doses of alemtuzumab as a treatment for relapsing-remitting multiple sclerosis (MS), in comparison with R...

An Observational Study for the Assessment of Compliance and Persistence to Rebif® Therapy of Patients With Relapsing-remitting Multiple Sclerosis (MS) and Evaluation of Potential Factors Influencing These Parameters

The present study aims to assess the adherence to therapy with interferon beta-1a (Rebif®) and at investigating potential factors that are involved in its outcome, in a representative sam...

Minocycline as add-on to Interferon Beta-1a (Rebif®) in Relapsing Remitting Multiple Sclerosis

This is a multicentric, double-blind, placebo-controlled, randomised, parallel group study to estimate the effect of minocycline as add-on to interferon beta 1a (IFN β-1a) in subjects wit...

PubMed Articles [8012 Associated PubMed Articles listed on BioPortfolio]

Neutralizing antibody production against Rebif® and ReciGen® in Relapsing-Remitting Multiple Sclerosis (RRMS) patients and its association with patient's disability.

Human recombinant interferon beta (IFN-β) is one of the first line treatments for Relapsing-Remitting Multiple Sclerosis (RRMS). However, the production of neutralizing antibodies (NAb) can impair it...

Matching-adjusted comparisons demonstrate better clinical outcomes with SC peginterferon beta-1a every two weeks than with SC interferon beta-1a three times per week.

Subcutaneous (SC) peginterferon beta-1a and SC interferon beta-1a (IFN beta-1a) have demonstrated efficacy in treating relapsing-remitting multiple sclerosis (RRMS) but have never been compared in dir...

Fulminant rebound of relapsing-remitting multiple sclerosis after discontinuation of dimethyl fumarate: A case report.

Rebound phenomena after discontinuation of different treatments for relapsing-remitting multiple sclerosis (RRMS) have previously been described. Systematic database research in PubMed did not show an...

Longitudinal analysis of verbal episodic memory in patients with relapsing-remitting multiple sclerosis.

A 4.5-year follow-up study was conducted to characterize baseline verbal episodic memory (VEM) and its behavior and to assess the effects of relapsing-remitting multiple sclerosis (RRMS) on this domai...

Tolerability and Safety Profile of a New Brand-Generic Product of Glatiramer Acetate in Iranian Patients with Relapsing-Remitting Multiple Sclerosis: An Observational Cohort Study.

The aim of this study was to evaluate the safety, tolerability, and efficacy of a brand-generic glatiramer acetate product in patients with relapsing-remitting multiple sclerosis over a 12-month perio...

Medical and Biotech [MESH] Definitions

A non-glycosylated form of interferon beta-1 that has a serine at position 17. It is used in the treatment of both RELAPSING-REMITTING MULTIPLE SCLEROSIS and CHRONIC PROGRESSIVE MULTIPLE SCLEROSIS.

A form of multiple sclerosis characterized by a progressive deterioration in neurologic function which is in contrast to the more typical relapsing remitting form. If the clinical course is free of distinct remissions, it is referred to as primary progressive multiple sclerosis. When the progressive decline is punctuated by acute exacerbations, it is referred to as progressive relapsing multiple sclerosis. The term secondary progressive multiple sclerosis is used when relapsing remitting multiple sclerosis evolves into the chronic progressive form. (From Ann Neurol 1994;36 Suppl:S73-S79; Adams et al., Principles of Neurology, 6th ed, pp903-914)

An interferon beta-1 subtype that has a methionine at position 1, a cysteine at position 17, and is glycosylated at position 80. It functions as an ANTI-VIRAL AGENT and IMMUNOMODULATOR and is used to manage the symptoms of RELAPSING-REMITTING MULTIPLE SCLEROSIS.

A random polymer of L-ALANINE, L-GLUTAMIC ACID, L-LYSINE, and L-TYROSINE that structurally resembles MYELIN BASIC PROTEIN. It is used in the treatment of RELAPSING-REMITTING MULTIPLE SCLEROSIS.

An autoimmune disorder mainly affecting young adults and characterized by destruction of myelin in the central nervous system. Pathologic findings include multiple sharply demarcated areas of demyelination throughout the white matter of the central nervous system. Clinical manifestations include visual loss, extra-ocular movement disorders, paresthesias, loss of sensation, weakness, dysarthria, spasticity, ataxia, and bladder dysfunction. The usual pattern is one of recurrent attacks followed by partial recovery (see MULTIPLE SCLEROSIS, RELAPSING-REMITTING), but acute fulminating and chronic progressive forms (see MULTIPLE SCLEROSIS, CHRONIC PROGRESSIVE) also occur. (Adams et al., Principles of Neurology, 6th ed, p903)

More From BioPortfolio on "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"

Advertisement
Quick Search
Advertisement
Advertisement

 

Relevant Topics

Multiple Sclerosis MS
Multiple sclerosis (MS) is the most common disabling neurological condition affecting 100,000 young adults in the UK. The condition results from autoimmune damage to myelin, causing interference in nerve signaling. Symptoms experienced depend on the pa...

Spinal Cord Disorders
The spinal cord is a bundle of nerves that runs down the middle of the back which carry signals back and forth between the body and brain. It is protected by vertebrae, which are the bone disks that make up the spine. An accident that damages the verte...

Neurology - Central Nervous System (CNS)
Alzheimer's Disease Anesthesia Anxiety Disorders Autism Bipolar Disorders Dementia Epilepsy Multiple Sclerosis (MS) Neurology Pain Parkinson's Disease Sleep Disorders Neurology is the branch of me...


Searches Linking to this Trial