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

NCT01297699 | Completed Phase 3

• 2 other identifiers: GRC-TCL-2010-012010-023841-31
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 9

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.

Conditions

Thyroid Associated Ophthalmopathies; Graves´ Ophthalmopathy; Thyroid Eye Disease

Keywords

Graves´ orbitopathy; Graves´ ophthalmopathy; Thyroid eye disease; Thyroid-associated ophthalmopathy; Tocilizumab; EUGOGO; CAS

Outcome Measures

Primary Outcomes (1)

• Drug efficacy will be established as a decrease in CAS (clinical activity score) by 2 or more points in a scale of 10.

  It will be measured before treatment (week -4 / 0), after treatment (week 16) and after the end of the follow-up (week 40).

Secondary Outcomes (4)

• Clinical response of patients who respond to treatment with tocilizumab

  It will be analyzed before treatment (week -4 / 0), after treatment (week 16) and once to follow up (week 40).

• Evaluate the patients quality of life associated with tocilizumab treatment, using SF-36

  It will be analyzed before treatment (week -4 / 0), after treatment (week 16) and once to follow up (week 40).

• Determine time to recurrence during follow-up period

  It is measured on a weeks-time scale assessed by the physician during patient follow-up visits.

• Safety as adverse events reported

  12 months

Study Arms (2)

Tocilizumab

EXPERIMENTAL

Drug: Tocilizumab (RoActemra®)

Sterile 0.9% Sodium Chloride

PLACEBO COMPARATOR

Drug: Sterile 0.9% Sodium Chloride

Interventions

Tocilizumab (RoActemra®) DRUG

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

Tocilizumab

Sterile 0.9% Sodium Chloride DRUG

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

Sterile 0.9% Sodium Chloride

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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
• History of reactions or anaphylactic allergic severe human monoclonal antibodies, humanized or murine
• Uncontrolled pathologies, whose exacerbations are treated with corticosteroids

Sponsors & Collaborators

• Hospital Clinico Universitario de Santiago: lead
• Fundación Ramón Domínguez: collaborator

Study Sites (9)

Hospital Clínico de Santiago

Santiago de Compostela, A Coruña, 15706, Spain

Location

Hospital Santa Creu i Sant Pau

Barcelona, Spain

Location

Hospital Clínico San Carlos

Madrid, Spain

Location

Hospital Universitario Ramón y Cajal

Madrid, Spain

Location

Centro Oftalmológico Moreiras

Santiago de Compostela, Spain

Location

Hospital Universitario Virgen del Rocío

Seville, Spain

Location

Hospital Universitario Virgen Macarena

Seville, Spain

Location

Hospital Universitario La Fe

Valencia, Spain

Location

Hospital Clínico Universitario Lozano Blesa

Zaragoza, Spain

Location

MeSH Terms

Conditions

Graves Ophthalmopathy

Interventions

tocilizumab; Sodium Chloride

Condition Hierarchy (Ancestors)

Eye Diseases, Hereditary; Eye Diseases; Graves Disease; Exophthalmos; Orbital Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Goiter; Thyroid Diseases; Endocrine System Diseases; Hyperthyroidism; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Study Officials

• Juan Jesús Gómez-Reino Carnota, MD, PhD

  Hospital Clínico de Santiago

  STUDY CHAIR

• Jóse V. Pérez Moreiras, MD, PhD

  Centro Oftalmológico Moreiras

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD, PhD

Study Record Dates

• First Submitted: February 16, 2011
• First Posted: February 17, 2011
• Study Start: March 1, 2012
• Primary Completion: October 1, 2015
• Study Completion: December 1, 2015
• Last Updated: January 20, 2016

Record last verified: 2016-01

Locations

ES (9)