Tocilizumab Treatment in Graves´ Ophthalmopathy (Graves´ Orbitopathy or Thyroid Eye Disease) (GRC)
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 Associated Ophthalmopathies Graves´ Ophthalmopathy Thyroid Eye Disease||Drug: Tocilizumab (RoActemra®) Drug: Sterile 0.9% Sodium Chloride||Phase 3|
|Study Design:||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
|Official Title:||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.|
- Drug efficacy will be established as a decrease in CAS (clinical activity score) by 2 or more points in a scale of 10. [ Time Frame: It will be measured before treatment (week -4 / 0), after treatment (week 16) and after the end of the follow-up (week 40). ]
- Clinical response of patients who respond to treatment with tocilizumab [ Time Frame: It will be analyzed before treatment (week -4 / 0), after treatment (week 16) and once to follow up (week 40). ]
- Evaluate the patients quality of life associated with tocilizumab treatment, using SF-36 [ Time Frame: It will be analyzed before treatment (week -4 / 0), after treatment (week 16) and once to follow up (week 40). ]
- Determine time to recurrence during follow-up period [ Time Frame: It is measured on a weeks-time scale assessed by the physician during patient follow-up visits. ]
- Safety as adverse events reported [ Time Frame: 12 months ]
|Study Start Date:||March 2012|
|Study Completion Date:||December 2015|
|Primary Completion Date:||October 2015 (Final data collection date for primary outcome measure)|
Drug: Tocilizumab (RoActemra®)
Single intravenous infusion of tocilizumab (8 mg/kg); every 4 weeks during 16 weeks.
|Placebo Comparator: Sterile 0.9% Sodium Chloride||
Drug: Sterile 0.9% Sodium Chloride
Single intravenous dip infusion of a sterile 0.9% sodium chloride, every four weeks during 16 weeks.
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01297699
|Hospital Clínico de Santiago|
|Santiago de Compostela, A Coruña, Spain, 15706|
|Hospital Santa Creu i Sant Pau|
|Hospital Clínico San Carlos|
|Hospital Universitario Ramón y Cajal|
|Centro Oftalmológico Moreiras|
|Santiago de Compostela, Spain|
|Hospital Universitario Virgen del Rocío|
|Hospital Universitario Virgen Macarena|
|Hospital Universitario La Fe|
|Hospital Clínico Universitario Lozano Blesa|
|Study Chair:||Juan Jesús Gómez-Reino Carnota, MD, PhD||Hospital Clínico de Santiago|
|Principal Investigator:||Jóse V. Pérez Moreiras, MD, PhD||Centro Oftalmológico Moreiras|