Graves' Dysthyroid OphthalmopathyPhase 1/2NCT00424151
Rituximab Treatment of Graves' Dysthyroid Ophthalmopathy
A Phase 1/2 study testing Rituximab in people with Graves' Dysthyroid Ophthalmopathy and Thyroid Related Orbitopathy, run by Silkiss, Rona Z., M.D., FACS at 2 sites in United States.
Trial summary
This study is designed to treat patients with Graves' disease with Rituximab in an attempt to prevent or reverse the physically deforming and debilitating consequences of this disease. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Graves' Dysthyroid Ophthalmopathy, Thyroid Related Orbitopathy
- What is being tested?
- Rituximab
- How many people
- 12 participants
- Where
- 2 sitesUnited States
- Study dates
- Dec 2006to Mar 2009
- Phase
- Phase 1/2
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients eighteen years of age or older.Diagnosed with Graves' dysthyroid ophthalmopathy within one year of presentation.
- Manifest significant ophthalmic findings of active Graves' disease. (Clinical activity score 4 or greater)
- Evidence of thyroid abnormality (hyper or hypo thyroid) prior to thyroid treatment
- Elevated thyroid stimulating immunoglobulin, antithyroid peroxidase antibody or antithyroglobulin antibody.
Who cannot join
- Long standing chronic disease. (greater than one year) History of ineffective prior orbital irradiation. Clinical activity score of less than 4.
- ANC < 1.5 x 103
- Hemoglobin: < 8.5 gm/dL
- Platelets: < 100,000/mm
- AST or ALT >2.5 x Upper Limit of Normal unless related to primary disease.
- IgG: < 5.6 mg/dl and IgM: < .55 mg/dl
Show all 24Show fewer
- Positive Hepatitis B or C serology (Hep B Surface antigen and Hep C antibody)
- History of positive HIV (HIV conducted during screening if applicable)
- Treatment with any investigational agent within 4 weeks of screening or 5 half-lives of the investigational drug (whichever is longer)
- Receipt of a live vaccine within 4 weeks prior to randomization
- Previous Treatment with Rituximab (MabThera® / Rituxan®)
- History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies
- History of recurrent significant infection or history of recurrent bacterial infections
- Known active bacterial, viral fungal mycobacterial, or other infection (including tuberculosis or atypical, mycobacterial disease, but excluding fungal infections of nail beds) or any major episode of infection requiring hospitalization or treatment with i.v. antibiotics within 4 weeks of screening or oral antibiotics within 2 weeks prior to screening
- Lack of peripheral venous access
- History of drug, alcohol, or chemical abuse within 6 months prior to screening
- Pregnancy (a negative serum pregnancy test should be performed for all women of childbearing potential within 7 days of treatment) or lactation
- Concomitant malignancies or previous malignancies, with the exception of adequately treated basal or squamous cell carcinoma of the skin or carcinoma in situ of the cervix
- History of psychiatric disorder that would interfere with normal participation in this protocol
- Significant cardiac, including significant or uncontrolled arrhythmia, or pulmonary disease (including obstructive pulmonary disease)
- History of systemic lupus erythematosis
- Any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that may affect the interpretation of the results or render the patient at high risk from treatment complications.
- Inability to comply with study and follow-up procedures
- -
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Simeon A. Lauer, MD
New York, New York, 10021
Rona Z. Silkiss, MD, FACS
Oakland, California, 94609
About this study
Official title: Rituximab Treatment of Graves' Dysthyroid Ophthalmopathy Phase I/II
This study is designed to treat patients with Graves' disease with Rituximab in an attempt to prevent or reverse the physically deforming and debilitating consequences of this disease.
Read the detailed description
Graves' Dysthyroid ophthalmopathy is an autoimmune disease characterized by inflammatory changes of the periocular and orbital region often in association with an underlying thyroid abnormality. These changes can be extremely debilitating and may lead to visual loss. Attempts at limiting or reversing the phenotypic expression of Graves' ophthalmopathy through aggressive orbital decompression surgery or targeting the inflammatory disease, using high dose systemic corticosteroids and/or orbital radiotherapy, have been limited to date by treatment ineffectiveness and co-morbidities. Selective B-cell depletion therapy offers a potential treatment alternative. This study is designed to treat patients with Graves' disease with Rituximab in an attempt to prevent or reverse the physically deforming and debilitating consequences of this disease.
- Being tested
- Rituximab
- Keywords
- Graves' Disease, Dysthyroid Ophthalmopathy, Thyroid related orbitopathy
- Medical subject headings
- Graves Disease, Graves Ophthalmopathy
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RituximabDrug
What is being measured
The primary outcome is the main question the study is designed to answer.
Clinical response to treatment, alteration in immunoglobulin levels
Measured: One year post infusion
To assess the safety and tolerability of Rituximab in Graves' dysthyroid disease up to 24 weeks. Adverse and serious adverse events during the study period, reasonably or probably related to Rituximab, will be assessed at each study visit up to 12 month
Measured: One year
Efficacy:
Measured: One year after treatment
A significant (25%) reduction in progression of Thyroid Associated Ophthalmopathy or disease activity as measured by the thyroid associated ophthalmopathy scale (University of British Columbia Thyroid Orbitopathy Inflammatory Score) up to 24 weeks.
Measured: One year
Secondary outcomes (3)
To evaluate for a reduction in disease activity as measured by:
Measured: One year
Reduction (25%) of elevated antibody levels- serum thyroid stimulating immunoglobulin (TSI), antithyroidperoxidase antibody (TPO) or antithyroglobulin levels at 24 weeks.
Measured: One year
MRI of the orbit with coronal and axial views to evaluate evidence of optic nerve crowding, muscle size reduction or decreased proptosis during treatment and follow up interval at 24 weeks.
Measured: Six months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Jan 2007 (estimated)
- Study startDec 2006
- Primary completionMar 2009
- Study completionMar 2009
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Graves' Dysthyroid OphthalmopathyStudies 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 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 12 participants (actual)
Sponsor and investigators
- Lead sponsor
- Silkiss, Rona Z., M.D., FACS
- Collaborators
- Lauer, Simeon, M.D., Reier, Alice M.D., Coleman, Morton M.D.
- Investigators
- Rona Z Silkiss, MD, Principal investigator, California Pacific Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00424151
- Sponsor's protocol ID
- U4126s
- Status last verified
- Oct 2010
- First submitted
- 17 Jan 2007
- Last updated
- 6 Oct 2010
- Results posted
- No
Study at a glance
From the registry record, last updated by the sponsor on 6 Oct 2010. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Rituximab Treatment of Graves' Dysthyroid Ophthalmopathy Phase I/II
- ClinicalTrials.gov ID
- NCT00424151
- Acronym / sponsor ID
- U4126s
- Keywords
- Graves' Disease, Dysthyroid Ophthalmopathy, Thyroid related orbitopathy
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 12 participants (actual)
- Lead sponsor
- Silkiss, Rona Z., M.D., FACS
- Collaborators
- Lauer, Simeon, M.D., Reier, Alice M.D., Coleman, Morton M.D.
- Study start
- Dec 2006
- Primary completion
- Mar 2009 (actual)
- Study completion
- Mar 2009 (actual)
- First posted
- 18 Jan 2007 (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.
This study is designed to treat patients with Graves' disease with Rituximab in an attempt to prevent or reverse the physically deforming and debilitating consequences of this disease.
Detailed description
Graves' Dysthyroid ophthalmopathy is an autoimmune disease characterized by inflammatory changes of the periocular and orbital region often in association with an underlying thyroid abnormality. These changes can be extremely debilitating and may lead to visual loss. Attempts at limiting or reversing the phenotypic expression of Graves' ophthalmopathy through aggressive orbital decompression surgery or targeting the inflammatory disease, using high dose systemic corticosteroids and/or orbital radiotherapy, have been limited to date by treatment ineffectiveness and co-morbidities. Selective B-cell depletion therapy offers a potential treatment alternative. This study is designed to treat patients with Graves' disease with Rituximab in an attempt to prevent or reverse the physically deforming and debilitating consequences of this disease.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Patients eighteen years of age or older.Diagnosed with Graves' dysthyroid ophthalmopathy within one year of presentation.
- Manifest significant ophthalmic findings of active Graves' disease. (Clinical activity score 4 or greater)
- Evidence of thyroid abnormality (hyper or hypo thyroid) prior to thyroid treatment
- Elevated thyroid stimulating immunoglobulin, antithyroid peroxidase antibody or antithyroglobulin antibody.
Key exclusion criteria (24 listed)
- Long standing chronic disease. (greater than one year) History of ineffective prior orbital irradiation. Clinical activity score of less than 4.
- ANC < 1.5 x 103
- Hemoglobin: < 8.5 gm/dL
- Platelets: < 100,000/mm
- AST or ALT >2.5 x Upper Limit of Normal unless related to primary disease.
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 |
|---|---|---|
| Rituximab | Drug | – |
Primary outcome
Clinical response to treatment, alteration in immunoglobulin levels
Time frame: One year post infusion
To assess the safety and tolerability of Rituximab in Graves' dysthyroid disease up to 24 weeks. Adverse and serious adverse events during the study period, reasonably or probably related to Rituximab, will be assessed at each study visit up to 12 month
Time frame: One year
Efficacy:
Time frame: One year after treatment
A significant (25%) reduction in progression of Thyroid Associated Ophthalmopathy or disease activity as measured by the thyroid associated ophthalmopathy scale (University of British Columbia Thyroid Orbitopathy Inflammatory Score) up to 24 weeks.
Time frame: One year
3 secondary outcomes
To evaluate for a reduction in disease activity as measured by:
Time frame: One year
Reduction (25%) of elevated antibody levels- serum thyroid stimulating immunoglobulin (TSI), antithyroidperoxidase antibody (TPO) or antithyroglobulin levels at 24 weeks.
Time frame: One year
MRI of the orbit with coronal and axial views to evaluate evidence of optic nerve crowding, muscle size reduction or decreased proptosis during treatment and follow up interval at 24 weeks.
Time frame: Six 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 6 Oct 2010.
Related trials for Graves' Dysthyroid Ophthalmopathy
Active, not recruitingPhase 4
Hydroxychloroquine in Mild Graves' Orbitopathy
Graves Ophthalmopathy
RecruitingObservational study
Early Risk Stratification of Thyroid Eye Disease in Newly Diagnosed Graves' Disease
Graves' Orbitopathy, Thyroid Eye Disease, TED
RecruitingPhase 1
Evaluation of ETHY-001 for Safety, Tolerability, and Clinical Activity in Thyroid Eye Disease
Thyroid Eye Disease (TED), Graves' Disease
Not yet recruitingPhase 2
Prophylactic Treatment of Graves Ophthalmopathy (GO) in Newly Diagnosed Graves' Disease (GD) With Atorvastatin (ATORGO)
Graves Disease, Graves Disease (Basedow's Disease)
RecruitingPhase 3
Study to Assess Linsitinib in Participants With Moderate to Severe Active Thyroid Eye Disease (TED)
Thyroid Eye Disease, TED, Graves Orbitopathy
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.
Rona Z Silkiss, MD principal investigator
California Pacific Medical Center
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Rituximab in people with Graves' Dysthyroid Ophthalmopathy and Thyroid Related Orbitopathy, run by Silkiss, Rona Z., M.D., FACS at 2 sites in United States.
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 4 inclusion and 24 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 6 Oct 2010. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. 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. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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?
Clinical response to treatment, alteration in immunoglobulin levels (time frame: One year post infusion). The study lists 4 primary outcomes in all. 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 6 Oct 2010.