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

NCT ID: NCT01297699

Last Updated: 2016-01-20

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 32 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-03-31
• Study Completion Date: 2015-12-31

Brief 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.

Detailed 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.

Conditions

Thyroid Associated Ophthalmopathies; Graves´ Ophthalmopathy; Thyroid Eye Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Tocilizumab

Group Type: EXPERIMENTAL

Tocilizumab (RoActemra®)

Intervention Type: DRUG

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

Sterile 0.9% Sodium Chloride

Group Type: PLACEBO_COMPARATOR

Sterile 0.9% Sodium Chloride

Intervention Type: DRUG

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

Interventions

Tocilizumab (RoActemra®)

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

Intervention Type: DRUG

Sterile 0.9% Sodium Chloride

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

Intervention Type: DRUG

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Fundación Ramón Domínguez

OTHER

Sponsor Role: collaborator

Hospital Clinico Universitario de Santiago

OTHER

Sponsor Role: lead

Responsible Party

Dr. Juan Jesus Gomez-Reino Carnota

MD, PhD

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Juan Jesús Gómez-Reino Carnota, MD, PhD

Role: STUDY_CHAIR

Hospital Clínico de Santiago

Jóse V. Pérez Moreiras, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Centro Oftalmológico Moreiras

Locations

Hospital Clínico de Santiago

Santiago de Compostela, A Coruña, 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 Universitario Virgen del Rocío

Seville, , Spain

Hospital Universitario Virgen Macarena

Seville, , Spain

Hospital Universitario La Fe

Valencia, , Spain

Hospital Clínico Universitario Lozano Blesa

Zaragoza, , Spain

Countries

Spain

Other Identifiers

2010-023841-31

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

GRC-TCL-2010-01

Identifier Type: -

Identifier Source: org_study_id