Tocilizumab Treatment in Graves´ Ophthalmopathy (Graves´ Orbitopathy or Thyroid Eye Disease)

Thyroid Eye Disease Clinical Trial

— GRC  

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.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01297699
• Other study ID #: GRC-TCL-2010-01
• Secondary ID: 2010-023841-31
• Status: Completed
• Phase: Phase 3
• First received: February 16, 2011
• Last updated: January 19, 2016
• Start date: March 2012
• Est. completion date: December 2015

Study information

• Verified date: January 2016
• Source: Hospital Clinico Universitario de Santiago
• Contact: n/a
• Is FDA regulated: No
• Health authority: Spain: Ethics CommitteeSpain: Spanish Agency of Medicines
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 32
• Est. completion date: December 2015
• Est. primary completion date: October 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 75 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Eye Diseases
• Graves Ophthalmopathy
• Graves´ Ophthalmopathy
• Thyroid Associated Ophthalmopathies
• Thyroid Diseases
• Thyroid Eye Disease

Intervention

Drug:
• Tocilizumab (RoActemra®)
Single intravenous infusion of tocilizumab (8 mg/kg); every 4 weeks during 16 weeks.
• Sterile 0.9% Sodium Chloride
Single intravenous dip infusion of a sterile 0.9% sodium chloride, every four weeks during 16 weeks.

Locations

Country	Name	City	State
Spain	Hospital Santa Creu i Sant Pau	Barcelona
Spain	Hospital Clínico San Carlos	Madrid
Spain	Hospital Universitario Ramón y Cajal	Madrid
Spain	Centro Oftalmológico Moreiras	Santiago de Compostela
Spain	Hospital Clínico de Santiago	Santiago de Compostela	A Coruña
Spain	Hospital Universitario Virgen del Rocío	Sevilla
Spain	Hospital Universitario Virgen Macarena	Sevilla
Spain	Hospital Universitario La Fe	Valencia
Spain	Hospital Clínico Universitario Lozano Blesa	Zaragoza

Sponsors (2)

Lead Sponsor	Collaborator
Hospital Clinico Universitario de Santiago	Fundación Ramón Domínguez

Country where clinical trial is conducted

Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Drug efficacy will be established as a decrease in CAS (clinical activity score) by 2 or more points in a scale of 10.		It will be measured before treatment (week -4 / 0), after treatment (week 16) and after the end of the follow-up (week 40).	No
Secondary	Clinical response of patients who respond to treatment with tocilizumab		It will be analyzed before treatment (week -4 / 0), after treatment (week 16) and once to follow up (week 40).	No
Secondary	Evaluate the patients quality of life associated with tocilizumab treatment, using SF-36		It will be analyzed before treatment (week -4 / 0), after treatment (week 16) and once to follow up (week 40).	No
Secondary	Determine time to recurrence during follow-up period		It is measured on a weeks-time scale assessed by the physician during patient follow-up visits.	No
Secondary	Safety as adverse events reported		12 months	Yes