Thyroid Associated OphthalmopathiesPhase 3GRCNCT01297699
Tocilizumab Treatment in Graves´ Ophthalmopathy (Graves´ Orbitopathy or Thyroid Eye Disease)
A Phase 3 study testing Tocilizumab (RoActemra®) and Sterile 0.9% Sodium Chloride in people with Thyroid Associated Ophthalmopathies and Graves´ Ophthalmopathy, run by Hospital Clinico Universitario de Santiago at 9 sites in Spain.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Thyroid Associated Ophthalmopathies, Graves´ Ophthalmopathy, Thyroid Eye Disease
- What is being tested?
- Tocilizumab (RoActemra®) and Sterile 0.9% Sodium Chloride
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 32 participants
- Where
- 9 sitesSpain
- Study dates
- Mar 2012to Dec 2015
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
None listed.
Who cannot join
- 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
Show all 16Show fewer
- 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
Trial locations and contacts
9 sites in 1 country.
9 sites in 1 country
Spain9 sites
Hospital Santa Creu i Sant Pau
Barcelona
Hospital Clínico San Carlos
Madrid
Hospital Universitario Ramón y Cajal
Madrid
Hospital Clínico de Santiago
Santiago de Compostela, A Coruña, 15706
Centro Oftalmológico Moreiras
Santiago de Compostela
Hospital Universitario Virgen del Rocío
Seville
Hospital Universitario Virgen Macarena
Seville
Hospital Universitario La Fe
Valencia
Hospital Clínico Universitario Lozano Blesa
Zaragoza
About this study
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.
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.
Read the 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.
- Being tested
- Tocilizumab (RoActemra®), Sterile 0.9% Sodium Chloride
- Keywords
- Graves´ orbitopathy, Graves´ ophthalmopathy, Thyroid eye disease, Thyroid-associated ophthalmopathy, Tocilizumab, EUGOGO, CAS
- Medical subject headings
- Graves Ophthalmopathy
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Tocilizumab (RoActemra®)Drug
Single intravenous infusion of tocilizumab (8 mg/kg); every 4 weeks during 16 weeks.
Sterile 0.9% Sodium ChlorideDrug
Single intravenous dip infusion of a sterile 0.9% sodium chloride, every four weeks during 16 weeks.
| Study group | Role | What they receive |
|---|---|---|
| Tocilizumab | Experimental | Not described Receives: Drug: Tocilizumab (RoActemra®) |
| Sterile 0.9% Sodium Chloride | Placebo comparator | Not described Receives: Drug: Sterile 0.9% Sodium Chloride |
What is being measured
The primary outcome is the main question the study is designed to answer.
Drug efficacy will be established as a decrease in CAS (clinical activity score) by 2 or more points in a scale of 10.
Measured: 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
Measured: 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
Measured: 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
Measured: It is measured on a weeks-time scale assessed by the physician during patient follow-up visits.
Safety as adverse events reported
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Feb 2011 (estimated)
- Study startMar 2012
- Primary completionOct 2015
- Study completionDec 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Thyroid Associated OphthalmopathiesStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 32 participants (actual)
Sponsor and investigators
- Lead sponsor
- Hospital Clinico Universitario de Santiago
- Sponsor type
- University, hospital or other
- Collaborators
- Fundación Ramón Domínguez
- Responsible party
- Principal investigator, Dr. Juan Jesus Gomez-Reino Carnota, Hospital Clinico Universitario de Santiago
- Investigators
- Juan Jesús Gómez-Reino Carnota, MD, PhD, Study chair, Hospital Clínico de SantiagoJóse V. Pérez Moreiras, MD, PhD, Principal investigator, Centro Oftalmológico Moreiras
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01297699
- Sponsor's protocol ID
- GRC-TCL-2010-01
- Other IDs
- 2010-023841-31
- Acronym
- GRC
- Status last verified
- Jan 2016
- First submitted
- 16 Feb 2011
- Last updated
- 20 Jan 2016
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 20 Jan 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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.
- ClinicalTrials.gov ID
- NCT01297699
- Acronym / sponsor ID
- GRC / GRC-TCL-2010-01
- Keywords
- Graves´ orbitopathy, Graves´ ophthalmopathy, Thyroid eye disease, Thyroid-associated ophthalmopathy, Tocilizumab, EUGOGO, CAS
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 32 participants (actual)
- Lead sponsor
- Hospital Clinico Universitario de SantiagoUniversity, hospital or other
- Collaborators
- Fundación Ramón Domínguez
- Study start
- Mar 2012
- Primary completion
- Oct 2015 (actual)
- Study completion
- Dec 2015 (actual)
- First posted
- 17 Feb 2011 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Tocilizumab | Experimental | Drug: Tocilizumab (RoActemra®) |
| Sterile 0.9% Sodium Chloride | Placebo comparator | Drug: Sterile 0.9% Sodium Chloride |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (0 listed)
Key exclusion criteria (16 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Tocilizumab (RoActemra®)Single intravenous infusion of tocilizumab (8 mg/kg); every 4 weeks during 16 weeks. | Drug | Tocilizumab |
| Sterile 0.9% Sodium ChlorideSingle intravenous dip infusion of a sterile 0.9% sodium chloride, every four weeks during 16 weeks. | Drug | Sterile 0.9% Sodium Chloride |
Primary outcome
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).
4 secondary outcomes
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).
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).
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.
Safety as adverse events reported
Time frame: 12 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Jan 2016.
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Prophylactic Treatment of Graves Ophthalmopathy (GO) in Newly Diagnosed Graves' Disease (GD) With Atorvastatin (ATORGO)
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Juan Jesús Gómez-Reino Carnota, MD, PhD study chair
Hospital Clínico de Santiago
Jóse V. Pérez Moreiras, MD, PhD principal investigator
Centro Oftalmológico Moreiras
9 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Tocilizumab (RoActemra®) and Sterile 0.9% Sodium Chloride in people with Thyroid Associated Ophthalmopathies and Graves´ Ophthalmopathy, run by Hospital Clinico Universitario de Santiago at 9 sites in Spain.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 0 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 20 Jan 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 9 sites in Spain. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the 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).). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Jan 2016.