Clinical Trial: Tocilizumab in the Treatment of Refractory Polymyositis and Dermatomyositis

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

Official Title: Tocilizumab in the Treatment of Refractory Polymyositis and Dermatomyositis

Brief Summary: The purpose of this multi-center pilot study is to determine if the drug tocilizumab (Actemra) is effective in the treatment of patients with refractory adult polymyositis (PM) and dermatomyositis (DM).

Detailed Summary:

Although there are several studies supporting the efficacy of tocilizumab (TCZ) in Rheumatoid Arthritis (RA) and systemic onset juvenile idiopathic arthritis, it's use in other autoimmune disorders has also been propose. A consensus statement on blocking the effects of IL-6 in RA and other autoimmune conditions has been recently published. IL-6 is involved in the growth and differentiation of many inflammatory cells. In addition to its initial role in triggering B-cell stimulating factor, it also induces T cell growth and differentiation and plays a critical role in both adaptive and innate immune responses. IL-6, produced by many cells including T cells, B cells, monocytes and endothelial cells, binds to its receptor (IL-6R) and subsequently triggers several intracellular pathways leading to the release of inflammatory mediators and stimulation of the immune system. Inhibition of IL-6 has been studied in phase II and III clinical trials of RA. It has led to a decrease in acute phase reactants and other indicators of chronic inflammation. IL-6 is also a potential therapeutic target in systemic sclerosis, and since IL-6 induces differentiation of B cells into antibody forming cells and contributes to T cells transforming into effector cells, its use in Systemic Lupus erythematosus (SLE) has also been suggested.

The use of TCZ in myositis proposed in this protocol is supported by the aforementioned rationale and its efficacy in other rheumatologic disorders. Patients with refractory polymyositis (PM) were treated with tocilizumab and responded favorably. In dermatomyositis, tissue inflammation implicates soluble cytokine networks contributing to disease pathogenesis. Work on a mouse model of myositis noted IL-6 as a mediator of muscle inflammation. Other investigators studying peripheral blood samples and clinical data on both adult and juvenile dermatomyositis (DM) noted t
Sponsor: University of Pittsburgh

Current Primary Outcome: Proportion of subjects meeting the definition of improvement (DOI) [ Time Frame: Week 4 through week 24 ]

The primary outcome will be to compare the proportion of subjects meeting the definition of improvement (DOI) at visits 2 through 7 during the 6-month treatment period between the treatment and placebo arms. The DOI for this trial is a composite utilizing the six CSM: 3 of 6 CSM improved by ≥ 20%, with no more than 2 CSM worsening by ≥25% (a worsening measure cannot be the MMT).


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Comparison of the time to first DOI between the 2 arms [ Time Frame: Week 4 through week 24 ]
    Comparing the proportion of subjects meeting DOI in the treatment and placebo arms on 2 consecutive visits, and determination of the time to flare [meeting the definition of worsening (DOW)] in those who earlier met the DOI.
  • frequency of defined adverse events between the treatment and placebo arms. [ Time Frame: Week 0 through week 36 ]

    We will statistically compare the frequency of the following adverse events between the treatment and placebo arms:

    • Infections including all opportunistic infections and non-serious infections as defined by those treated with IV anti-infectives
    • Myocardial infarction/acute coronary syndrome
    • GI perforation and related events
    • Malignancies
    • Hypersensitivity reactions and anaphylaxis
    • Demyelinating disorders
    • Stroke
    • Bleeding events
    • Hepatic events

    Similarly, we will analyze the proportion of serious adverse events between the treatment and placebo arms. In addition, the number and percent of patients with AEs during the treatment period will be summarized.



Original Secondary Outcome: Same as current

Information By: University of Pittsburgh

Dates:
Date Received: January 17, 2014
Date Started: October 2014
Date Completion: April 2018
Last Updated: October 26, 2016
Last Verified: October 2016