ScleritisPhase 1/2NCT00415506
Rituximab in the Treatment of Scleritis and Non-Infectious Orbital Inflammation
A Phase 1/2 study testing Rituximab in people with Scleritis and Orbital Disease, run by Oregon Health and Science University at 1 site in United States.
Trial summary
The purpose of this study is to assess the safety and tolerability of Rituximab in refractory scleritis and non-infectious orbital inflammation. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Scleritis, Orbital Disease
- What is being tested?
- Rituximab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 siteUnited States
- Study dates
- Jan 2007to Mar 2011
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 with non-infectious scleritis or idiopathic orbital inflammatory disease requiring chronic immunosuppressive treatment for disease control.
- Intolerance, failure to respond to, or inability to taper below prednisone > 10mg/day in addition to one systemic immunosuppressive (such as methotrexate, azathioprine, mycophenolate mofetil, cyclosporine, cyclophosphamide, or chlorambucil).
- Patients must be on a stable dosage of prednisone and at least one steroid-sparing agent in the 30 days prior to screening/enrollment.
- Active disease will be defined using physician judgment and supported by patient and physician global ocular disease assessment of > 5 cm on a 10cm visual analog scale anchored by the words "Inactive Eye Disease" at 0 cm point and "Extremely Active Eye Disease" at the 10cm point. Investigator discretion may apply in some cases.
- Selected patients who are on biological agents such as TNF blockers etanercept, infliximab and adalimumab with ongoing ocular disease are acceptable. There will be an 8 week washout period of etanercept and a 12 week washout period for infliximab and adalimumab before patients are dosed with rituximab.
- In patients with concomitant systemic autoimmune diseases including RA, SLE, Sjogrens, Wegener's granulomatosis the systemic disease must be sufficiently stable and not life threatening to allow tapering of steroids and/or immunosuppressive agents thus allowing assessment of ocular effect of rituximab.
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- Adults of both genders > 18 years old. There is no upper age limit as long as there are no other disqualifying health conditions.
- Have had a recent (<3 months old) PPD skin test and are considered eligible according to the tuberculosis (TB) screening, eligibility assessment, and prevention rules defined in Appendix C.
- Screening laboratory test results should be acceptable to the Investigator prior to placing a patient on study drug.
- Must have a chest radiograph within 3 months prior to first infusion with no evidence of malignancy, infection or fibrosis.
- Adequate renal function as indicated by normal BUN and creatinine levels.
Who cannot join
- Untreated thyroid disease
- Organ threatening systemic disease as evidenced by rapidly progressive glomerulonephritis, pulmonary hemorrhage or respiratory failure, seizures or psychosis, progressive neuropathy or myopathy
- General Safety \& Laboratory Exclusion Criteria
- Patients will be excluded from the study based on the following criteria:
- Hemoglobin: < 8.5 gm/dL
- Platelets: < 100,000/mm
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- AST or ALT >2.5 x Upper Limit of Normal unless related to primary disease.
- 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
- Unstable steroid dose in the past 4 weeks
- Lack of peripheral venous access
- History of drug, alcohol, or chemical abuse within 6 months prior to screening
- Pregnancy (a negative serum pregnancy for all women of childbearing potential at screening and negative urine pregnancy test prior to each infusion) or lactation
- Concomitant or previous malignancies, with the exception of curatively resected non-melanoma skin carcinomas or carcinoma in situ of the cervix
- History of psychiatric disorder that would interfere with normal participation in this protocol
- Significant cardiac or pulmonary disease (including obstructive pulmonary disease)
- 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
1 site in 1 country.
United States1 site
Oregon Health & Science University
Portland, Oregon, 97239
About this study
Official title: A PhaseI/II Prospective, Randomized, Dose-Ranging Pilot Study of Rituximab in the Treatment of Refractory Scleritis and Non-Infectious Orbital Inflammation
The purpose of this study is to assess the safety and tolerability of Rituximab in refractory scleritis and non-infectious orbital inflammation.
- Conditions
- Scleritis, Orbital Disease
- Being tested
- Rituximab
- Medical subject headings
- Scleritis, Orbital Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RituximabDrug
Two 500 or 1000mg infusions over 2 weeks with the option of retreating after 6 months if initial improvement was seen.
| Study group | Role | What they receive |
|---|---|---|
| Scleritis | Experimental | Subjects with Scleritis Receives: Drug: Rituximab |
| Orbital Inflammation | Experimental | Subjects with Orbital Inflammation Receives: Drug: Rituximab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Reduction of Medications
Reduction (decrease in dosage) of systemic corticosteroids or immunosuppressive therapy by at least 50% by 24 weeks.
Measured: 24 Weeks
Improved Control of Inflammation
For patients with scleritis, disease activity as measured by a modified grading system first described by McCluskey et al. (McCluskey and Wakefield 1987; McCluskey and Wakefield 1991). Improvement in scleritis activity will be defined as a reduction in this grading score of 2 or more, or an overall score of 4 or less by 24 weeks.
For patients with orbital inflammation, disease activity as measured by a modified grading system first devised by Werner (Werner 1977). Improvement in orbital inflammation will be defined as a reduction in this grading score of 2 or more, or an overall score of 3 or less.
Measured: 24 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Dec 2006 (estimated)
- Study startJan 2007
- Primary completionMar 2011
- Study completionMar 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for ScleritisStudies of the same condition, open and under way.
- More trials run by Oregon Health and Science UniversityThe sponsor's other registered studies.
- 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
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- Oregon Health and Science University
- Sponsor type
- University, hospital or other
- Collaborators
- Genentech, Inc.
- Responsible party
- Principal investigator, Jim Rosenbaum, Oregon Health and Science University
- Investigators
- James T Rosenbaum, MD, Principal investigator, Oregon Health and Science UniversityEric B Suhler, MD, Study director, Oregon Health and Science University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00415506
- Sponsor's protocol ID
- e1529
- Status last verified
- Aug 2013
- First submitted
- 21 Dec 2006
- Last updated
- 16 Aug 2013
- Results posted
- Yes, on ClinicalTrials.gov
Publications
Suhler EB, Lim LL, Beardsley RM, Giles TR, Pasadhika S, Lee ST, de Saint Sardos A, Butler NJ, Smith JR, Rosenbaum JT. Rituximab therapy for refractory orbital inflammation: results of a phase 1/2, dose-ranging, randomized clinical trial. JAMA Ophthalmol. 2014 May;132(5):572-8. doi: 10.1001/jamaophthalmol.2013.8179.
PubMed 24652467
Study at a glance
From the registry record, last updated by the sponsor on 16 Aug 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A PhaseI/II Prospective, Randomized, Dose-Ranging Pilot Study of Rituximab in the Treatment of Refractory Scleritis and Non-Infectious Orbital Inflammation
- ClinicalTrials.gov ID
- NCT00415506
- Acronym / sponsor ID
- e1529
- Conditions
- Scleritis, Orbital Disease
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- Oregon Health and Science UniversityUniversity, hospital or other
- Collaborators
- Genentech, Inc.
- Study start
- Jan 2007
- Primary completion
- Mar 2011 (actual)
- Study completion
- Mar 2011 (actual)
- First posted
- 25 Dec 2006 (estimated)
- Results
- Posted 8 Aug 2013
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to assess the safety and tolerability of Rituximab in refractory scleritis and non-infectious orbital inflammation.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Scleritis | Experimental | Drug: RituximabSubjects with Scleritis |
| Orbital Inflammation | Experimental | Drug: RituximabSubjects with Orbital Inflammation |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Patients with non-infectious scleritis or idiopathic orbital inflammatory disease requiring chronic immunosuppressive treatment for disease control.
- Intolerance, failure to respond to, or inability to taper below prednisone > 10mg/day in addition to one systemic immunosuppressive (such as methotrexate, azathioprine, mycophenolate mofetil, cyclosporine, cyclophosphamide, or chlorambucil).
- Patients must be on a stable dosage of prednisone and at least one steroid-sparing agent in the 30 days prior to screening/enrollment.
- Active disease will be defined using physician judgment and supported by patient and physician global ocular disease assessment of > 5 cm on a 10cm visual analog scale anchored by the words "Inactive Eye Disease" at 0 cm point and "Extremely Active Eye Disease" at the 10cm point. Investigator discretion may apply in some cases.
- Selected patients who are on biological agents such as TNF blockers etanercept, infliximab and adalimumab with ongoing ocular disease are acceptable. There will be an 8 week washout period of etanercept and a 12 week washout period for infliximab and adalimumab before patients are dosed with rituximab.
Key exclusion criteria (24 listed)
- Untreated thyroid disease
- Organ threatening systemic disease as evidenced by rapidly progressive glomerulonephritis, pulmonary hemorrhage or respiratory failure, seizures or psychosis, progressive neuropathy or myopathy
- General Safety \& Laboratory Exclusion Criteria
- Hemoglobin: < 8.5 gm/dL
- Platelets: < 100,000/mm
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 |
|---|---|---|
| RituximabTwo 500 or 1000mg infusions over 2 weeks with the option of retreating after 6 months if initial improvement was seen. | Drug | Orbital Inflammation, Scleritis |
Primary outcome
Reduction of Medications
Time frame: 24 Weeks
Reduction (decrease in dosage) of systemic corticosteroids or immunosuppressive therapy by at least 50% by 24 weeks.
Improved Control of Inflammation
Time frame: 24 weeks
For patients with scleritis, disease activity as measured by a modified grading system first described by McCluskey et al. (McCluskey and Wakefield 1987; McCluskey and Wakefield 1991). Improvement in scleritis activity will be defined as a reduction in this grading score of 2 or more, or an overall score of 4 or less by 24 weeks. For patients with orbital inflammation, disease activity as measured by a modified grading system first devised by Werner (Werner 1977). Improvement in orbital inflammation will be defined as a reduction in this grading score of 2 or more, or an overall score of 3 or less.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Aug 2013.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 24652467Suhler EB, Lim LL, Beardsley RM, Giles TR, Pasadhika S, Lee ST, de Saint Sardos A, Butler NJ, Smith JR, Rosenbaum JT. Rituximab therapy for refractory orbital inflammation: results of a phase 1/2, dose-ranging, randomized clinical trial. JAMA Ophthalmol. 2014 May;132(5):572-8. doi: 10.1001/jamaophthalmol.2013.8179.
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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.
James T Rosenbaum, MD principal investigator
Oregon Health and Science University
Eric B Suhler, MD study director
Oregon Health and Science University
1 site 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 Scleritis and Orbital Disease, run by Oregon Health and Science University at 1 site 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 11 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 16 Aug 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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?
Yes. Results are posted in the registry (first posted 8 Aug 2013). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Reduction of Medications (time frame: 24 Weeks). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00415506, which also lists 1 linked publication.
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 16 Aug 2013.