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

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2014 by Hospital Clinico Universitario de Santiago
Sponsor:
Collaborator:
Fundación Ramón Domínguez
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: July 23, 2014
Last verified: July 2014

February 16, 2011
July 23, 2014
March 2012
June 2015   (final data collection date for primary outcome measure)
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: No ]
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 ]
Complete list of historical versions of study NCT01297699 on ClinicalTrials.gov Archive Site
  • 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). ] [ Designated as safety issue: No ]
  • 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). ] [ Designated as safety issue: No ]
  • 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. ] [ Designated as safety issue: No ]
  • Safety as adverse events reported [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
  • 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 ]
Not Provided
Not Provided
 
Tocilizumab Treatment in Graves´ Ophthalmopathy (Graves´ Orbitopathy or Thyroid Eye Disease)
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

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 for this patients..

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.

Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
  • Thyroid Associated Ophthalmopathies
  • Graves´ Ophthalmopathy
  • Thyroid Eye Disease
  • Drug: Tocilizumab (RoActemra®)
    Single intravenous infusion of tocilizumab (8 mg/kg); every 4 weeks during 16 weeks.
  • Drug: Sterile 0.9% Sodium Chloride
    Single intravenous dip infusion of a sterile 0.9% sodium chloride, every four weeks during 16 weeks.
  • Experimental: Tocilizumab
    Intervention: Drug: Tocilizumab (RoActemra®)
  • Placebo Comparator: Sterile 0.9% Sodium Chloride
    Intervention: Drug: Sterile 0.9% Sodium Chloride
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
32
June 2016
June 2015   (final data collection date for primary outcome measure)

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
Both
18 Years to 75 Years
No
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
Spain
 
NCT01297699
GRC-TCL-2010-01, 2010-023841-31
No
Dr. Juan Jesus Gomez-Reino Carnota, Hospital Clinico Universitario de Santiago
Hospital Clinico Universitario de Santiago
Fundación Ramón Domínguez
Study Chair: Juan Jesús Gómez-Reino Carnota, MD, PhD Hospital Clínico de Santiago
Principal Investigator: Jóse V. Pérez Moreiras, MD, PhD Centro Oftalmológico Moreiras
Hospital Clinico Universitario de Santiago
July 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP