Trial | NCT01297699  Report issue

Title

Tocilizumab Treatment in Graves´ Ophthalmopathy (Graves´ Orbitopathy or Thyroid Eye Disease)
Clinical Trial Phase III, Parallel Group, Randomized, Placebo-controlled, Double-blind, Multicenter Study to Evaluate the Efficacy and Safety of Tocilizumab Administration in Patients With Moderate-to-severe or Sight-threatening Graves' Ophthalmopathy (GO), That Had Not Responded Adequately to Treatment With Intravenous Corticoid Pulses.

  • Phase

    Phase 3

  • Study Type

    Interventional

  • Status

    Completed No Results Posted

  • Study Participants

    32
The purpose is to investigate tocilizumab administration in patients with moderately to severely or sight-threatening GO (Graves' ophthalmopathy) without response to treatment with corticoid intravenous pulses. Currently, these patients only have surgery as therapeutic alternative.

The principal aim of this study is to evaluate efficacy and safety of tocilizumab treatment in order to provide a better alternative to surgery for this patients.
Thyroid orbitopathy or Graves´orbitopathy (GO) is manifested for inflammation of the orbital and periorbital soft tissues. Ten percent of patients with GO will have long-term serious eye problems.

The cause of the GO is complex. Autoreactive T cells recognize an autoantigen, the TSH receptor present in the orbit and thyroid follicular cell, secrete cytokines (IL-6), which stimulate the fibroblasts to synthesize glycosaminoglycan, which draws liquid produce periorbital edema and muscle, causing exophthalmos.

This approach suggests that inhibition of IL-6 can be an effective treatment for this problem on the basis that tocilizumab specifically binds to the receptors of the IL-6, both soluble and membrane-bound. Tocilizumab has been shown to inhibit signaling mediated for IL-6Rm IL-6Rs.
Study Started
Mar 31
2012
Primary Completion
Oct 31
2015
Study Completion
Dec 31
2015
Last Update
Jan 20
2016
Estimate

Drug Tocilizumab (RoActemra®)

Single intravenous infusion of tocilizumab (8 mg/kg); every 4 weeks during 16 weeks.

Drug Sterile 0.9% Sodium Chloride

Single intravenous dip infusion of a sterile 0.9% sodium chloride, every four weeks during 16 weeks.

Tocilizumab Experimental

Sterile 0.9% Sodium Chloride Placebo Comparator

Criteria 

Principal Inclusion Criteria:

Patients diagnosed GO with CAS ≥ 4 and an index of severity, according EUGOGO guidelines, 1. moderately to severely or 2. sight-threatening GO, after receiving corticosteroid pulse treatment due to:

Poor response to intravenous corticosteroid pulses Or
Recurrence of the GO, after treatment with intravenous corticosteroids

Exclusion Criteria:

Orbital decompression surgery needed immediately
Active smoker
Patients who could need treatment with radioactive iodine or thyroidectomy during the study
Pregnant patient or patient who is planning to become pregnant during the study
History of chronic recurrent or active infection
History of intestinal ulceration or diverticulitis
Patients with a history of chronic liver disease or liver disorders: Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) above 5 times upper limit of normal (ULN)
History of HIV, hepatitis C or hepatitis B Positive
Neutrophil count < 0.5 × 109/L or a platelet count < 50×103/μL
Simultaneous use or contraindications to the use of immunosuppressive agents
A treatment with another investigational drug within four weeks of selection or five half-lives of study drug
Cardiovascular or cerebrovascular disease clinically significant
Uncontrolled diabetes mellitus
Use of corticosteroids during four weeks before to inclusion period
History of reactions or anaphylactic allergic severe human monoclonal antibodies, humanized or murine
Uncontrolled pathologies, whose exacerbations are treated with corticosteroids
No Results Posted