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

This study is currently recruiting participants.
Verified February 2013 by Hospital Clinico Universitario de Santiago
Sponsor:
Information provided by (Responsible Party):
Dr. Juan Jesus Gomez-Reino Carnota, Hospital Clinico Universitario de Santiago
ClinicalTrials.gov Identifier:
NCT01297699
First received: February 16, 2011
Last updated: February 6, 2013
Last verified: February 2013
  Purpose

The purpose of this study 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 the efficacy and safety of tocilizumab treatment in order to provide a better alternative to surgery.


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

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, 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

Resource links provided by NLM:


Further study details as provided by Hospital Clinico Universitario de Santiago:

Primary Outcome Measures:
  • 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). ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Clinical response of patients 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). ] [ Designated as safety issue: No ]
  • Evaluate the patients quality of life associated with tocilizumab treatment, by the quality of life questionnaires: SF-36 and GO-QoL [ Time Frame: It will be analyzed before treatment (week -4 / 0), after treatment (week 16) and once to follow up (week 40). ] [ Designated as safety issue: No ]
  • Determine time to recurrence during the observation period [ Time Frame: It is measured on a weeks-time scale assessed by the physician during patient follow-up visits. ] [ Designated as safety issue: Yes ]
  • Safety as adverse events reported by patients or diagnosed by the doctor. [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 32
Study Start Date: March 2012
Estimated Study Completion Date: November 2014
Estimated Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Tocilizumab Drug: Tocilizumab (RoActemra®)
Single intravenous infusion of tocilizumab (8 mg/kg); every 4 weeks for 16.
Placebo Comparator: IV saline Drug: Sterile 0.9% Sodium Chloride
Single intravenous dip infusion of a sterile 0.9% sodium chloride, every four weeks for 16

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.

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01297699

Contacts
Contact: Juan Jesús Gómez-Reino Carnota, MD, PhD (+34) 981 95 10 36 Juan.Jesus.Gomez-Reino.Carnota@sergas.es
Contact: María Teresa Oreiro García, PhD (+34) 981 95 50 41 maria.teresa.oreiro.garcia@sergas.es

Locations
Spain
Hospital Clínico de Santiago Recruiting
Santiago de Compostela, A Coruña, Spain, 15706
Contact: Juan Jesús Gómez-Reino Carnota, MD, PhD    (+34) 981 95 10 36    Juan.Jesus.Gomez-Reino.Carnota@sergas.es   
Contact: María Teresa Oreiro García, PhD    (+34) 981 95 50 41    maria.teresa.oreiro.garcia@sergas.es   
Principal Investigator: Júan J. Gómez-Reino Carnota, MD, PhD         
Hospital Santa Creu i Sant Pau Recruiting
Barcelona, Spain
Contact: Fernándo Mª Rodríguez Álvarez, MD         
Principal Investigator: Fernando Mª Rodríguez Álvarez, MD         
Hospital Universitario Ramón y Cajal Recruiting
Madrid, Spain
Contact: Marco Sales Sanz, MD, PhD         
Principal Investigator: Marco Sales Sanz, MD, PhD         
Hospital Universitario Fuenlabrada Not yet recruiting
Madrid, Spain
Contact: Nicolás Toledano Fernández, MD, PhD         
Principal Investigator: Nicolás Toledano Fernández, MD, PhD         
Hospital Clínico San Carlos Recruiting
Madrid, Spain
Contact: Ángel Romo López, MD         
Principal Investigator: Ángel Romo López, MD         
Centro Oftalmológico Moreiras Recruiting
Santiago de Compostela, Spain
Contact: Jose V Pérez Moreiras, MD, PhD         
Principal Investigator: José V. Pérez Moreiras, MD, PhD         
Hospital Universitario Virgen del Rocío Not yet recruiting
Sevilla, Spain
Contact: Aurora del Estad Cabello, MD         
Principal Investigator: Aurora del Estad Cabello, MD         
Hospital Universitario Virgen Macarena Not yet recruiting
Sevilla, Spain
Contact: María Gessa Sorroche         
Principal Investigator: Maíra Gessa Sorroche, MD         
Hospital Universitario La Fe Recruiting
Valencia, Spain
Contact: Enrique España Gregori, MD, PhD         
Principal Investigator: Enrique España Gregori, MD, PhD         
Hospital Clínico Universitario Lozano Blesa Not yet recruiting
Zaragoza, Spain
Contact: Jesús Mª Castillo Laguarta, MD         
Principal Investigator: Jesús Mª Castillo Laguarta, MD         
Sponsors and Collaborators
Hospital Clinico Universitario de Santiago
Investigators
Study Chair: Juan Jesús Gómez-Reino Carnota, MD, PhD Hospital Clínico de Santiago
Principal Investigator: Jóse V. Pérez Moreiras, MD, PhD Centro Oftalmológico Moreiras
  More Information

No publications provided

Responsible Party: Dr. Juan Jesus Gomez-Reino Carnota, MD, PhD, Hospital Clinico Universitario de Santiago
ClinicalTrials.gov Identifier: NCT01297699     History of Changes
Other Study ID Numbers: GRC-TCL-2010-01, 2010-023841-31
Study First Received: February 16, 2011
Last Updated: February 6, 2013
Health Authority: Spain: Ethics Committee
Spain: Spanish Agency of Medicines

Keywords provided by Hospital Clinico Universitario de Santiago:
Graves´ orbitopathy
Graves´ ophthalmopathy
Thyroid eye disease
Thyroid-associated ophthalmopathy
Tocilizumab
EUGOGO
CAS

Additional relevant MeSH terms:
Eye Diseases
Graves Ophthalmopathy
Eye Diseases, Hereditary
Thyroid Diseases
Endocrine System Diseases
Graves Disease
Exophthalmos
Orbital Diseases
Goiter
Hyperthyroidism
Autoimmune Diseases
Immune System Diseases

ClinicalTrials.gov processed this record on April 17, 2014