- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01297699
Tocilizumab Treatment in Graves´ Ophthalmopathy (Graves´ Orbitopathy or Thyroid Eye Disease) (GRC)
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 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.
Study Overview
Status
Intervention / Treatment
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.
Study Type
Enrollment (Actual)
Phase
- Phase 3
Contacts and Locations
Study Locations
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-
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Barcelona, Spain
- Hospital Santa Creu i Sant Pau
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Madrid, Spain
- Hospital Clinico San Carlos
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Madrid, Spain
- Hospital Universitario Ramon Y Cajal
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Santiago de Compostela, Spain
- Centro Oftalmológico Moreiras
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Sevilla, Spain
- Hospital Universitario Virgen del Rocío
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Sevilla, Spain
- Hospital Universitario Virgen Macarena
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Valencia, Spain
- Hospital Universitario La Fe
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Zaragoza, Spain
- Hospital Clinico Universitario Lozano Blesa
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A Coruña
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Santiago de Compostela, A Coruña, Spain, 15706
- Hospital Clínico de Santiago
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-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Double
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Tocilizumab
|
Single intravenous infusion of tocilizumab (8 mg/kg); every 4 weeks during 16 weeks.
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Placebo Comparator: Sterile 0.9% Sodium Chloride
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Single intravenous dip infusion of a sterile 0.9% sodium chloride, every four weeks during 16 weeks.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
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).
|
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
Outcome Measure |
Time Frame |
---|---|
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).
|
It will be analyzed before treatment (week -4 / 0), after treatment (week 16) and once to follow up (week 40).
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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).
|
It will be analyzed before treatment (week -4 / 0), after treatment (week 16) and once to follow up (week 40).
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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.
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It is measured on a weeks-time scale assessed by the physician during patient follow-up visits.
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Safety as adverse events reported
Time Frame: 12 months
|
12 months
|
Collaborators and Investigators
Collaborators
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
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- GRC-TCL-2010-01
- 2010-023841-31 (EudraCT Number)
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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