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

Hospital Clinico Universitario de Santiago

Status and phase

Completed

Phase 3

Conditions

Graves´ Ophthalmopathy

Thyroid Associated Ophthalmopathies

Thyroid Eye Disease

Treatments

Drug: Tocilizumab (RoActemra®)

Drug: Sterile 0.9% Sodium Chloride

Study type

Interventional

Funder types

Other

Identifiers

NCT01297699

GRC-TCL-2010-01

2010-023841-31 (EudraCT Number)

Details and patient eligibility

About

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.

Full 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.

Enrollment

32 patients

Sex

All

Ages

18 to 75 years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion 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