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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01297699
Recruitment Status : Completed
First Posted : February 17, 2011
Last Update Posted : January 20, 2016
Fundación Ramón Domínguez
Information provided by (Responsible Party):
Dr. Juan Jesus Gomez-Reino Carnota, Hospital Clinico Universitario de Santiago

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.

Condition or disease Intervention/treatment Phase
Thyroid Associated Ophthalmopathies Graves´ Ophthalmopathy Thyroid Eye Disease Drug: Tocilizumab (RoActemra®) Drug: Sterile 0.9% Sodium Chloride Phase 3

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 32 participants
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.
Study Start Date : March 2012
Actual Primary Completion Date : October 2015
Actual Study Completion Date : December 2015

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Eye Diseases
Drug Information available for: Tocilizumab

Arm Intervention/treatment
Experimental: Tocilizumab 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.

Primary Outcome Measures :
  1. 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). ]

Secondary Outcome Measures :
  1. 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). ]
  2. 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). ]
  3. 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. ]
  4. Safety as adverse events reported [ Time Frame: 12 months ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01297699

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Hospital Clínico de Santiago
Santiago de Compostela, A Coruña, Spain, 15706
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
Sevilla, Spain
Hospital Universitario Virgen Macarena
Sevilla, Spain
Hospital Universitario La Fe
Valencia, Spain
Hospital Clínico Universitario Lozano Blesa
Zaragoza, Spain
Sponsors and Collaborators
Hospital Clinico Universitario de Santiago
Fundación Ramón Domínguez
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Study Chair: Juan Jesús Gómez-Reino Carnota, MD, PhD Hospital Clínico de Santiago
Principal Investigator: Jóse V. Pérez Moreiras, MD, PhD Centro Oftalmológico Moreiras
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Responsible Party: Dr. Juan Jesus Gomez-Reino Carnota, MD, PhD, Hospital Clinico Universitario de Santiago Identifier: NCT01297699    
Other Study ID Numbers: GRC-TCL-2010-01
2010-023841-31 ( EudraCT Number )
First Posted: February 17, 2011    Key Record Dates
Last Update Posted: January 20, 2016
Last Verified: January 2016
Keywords provided by Dr. Juan Jesus Gomez-Reino Carnota, Hospital Clinico Universitario de Santiago:
Graves´ orbitopathy
Graves´ ophthalmopathy
Thyroid eye disease
Thyroid-associated ophthalmopathy
Additional relevant MeSH terms:
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Eye Diseases
Graves Ophthalmopathy
Thyroid Diseases
Endocrine System Diseases
Eye Diseases, Hereditary
Graves Disease
Orbital Diseases
Genetic Diseases, Inborn
Autoimmune Diseases
Immune System Diseases