UveitisPhase 2NCT00001863
Leflunomide to Treat Uveitis
A Phase 2 study testing Leflunomide in people with Uveitis, run by National Eye Institute (NEI) at 1 site in United States.
Trial summary
This study will investigate the safety and effectiveness of the drug Leflunomide to treat uveitis-an inflammation of the eye caused by an immune system abnormality. Leflunomide suppresses immune system activity and has been shown to control autoimmune diseases, such as arthritis (joint inflammation), in animals. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Uveitis
- What is being tested?
- Leflunomide
- How many people
- 16 participants
- Where
- 1 siteUnited States
- Study dates
- Mar 1999to Feb 2003
- Phase
- Phase 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 Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Diagnosis of current intermediate or posterior uveitis, or panuveitis.
- Current evidence of active intraocular inflammation based on the presence of vitreous haze, active retinal lesions, retinal vasculitis, or cystoid macular edema.
- 16 years of age or older.
- Visual acuity of 73 letters or fewer (Snellen equivalent: 20/40 or worse) in at least one eye.
- The ability to understand and sign an informed consent form which must be obtained prior to randomization.
- The diagnosis of intermediate uveitis requires the presence of vitritis and either peripheral retinal vascular disease, cellular debris in the inferior vitreous (vitreous snowballs), exudate on the pars plana, or peripheral retinal infiltrates. The diagnosis of posterior uveitis requires the presence of infiltrative retinal lesions involving the posterior pole of the eye, usually with vitritis and often times with cystoid macular edema. The amount of cystoid macular edema will be graded by a standard protocol using Fluorescein Angiogram. The diagnosis of pan-uveitis requires the finding of active anterior segment inflammation, vitritis, and infiltrative retinal lesions.
Who cannot join
- Ocular or systemic disease requiring greater than 1 mg/kg/day of prednisone or greater than 80 mg qd if patients weigh more than 80 kg, or requiring other systemic immunosuppressants.
- Periocular injections of corticosteroids within the previous 4 weeks.
- Intolerance or contraindications to corticosteroids.
- Female who is pregnant or lactating.
- Patient refuses to use contraception during the study and 24 months after termination of active study therapy or undergo a cholestyramine washout regimen or an activated charcoal regimen under the care of a physician following termination of study therapy, if child-bearing or fathering potential exists.
- Patients with Behcet's disease.
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- Use of Latanoprost within 2 weeks prior to enrollment, or current or likely need for Latanoprost during the course of the study.
- Hypersensitivity to fluorescein dye.
- Contraindications to use of steroids at dose and schedule.
- SGOT (AST) or SGPT(ALT) greater than or equal to 2 times the upper limit of normal.
- Allergic or hypersensitivity to leflunomide or any excipients.
Trial locations and contacts
1 site in 1 country.
United States1 site
National Eye Institute (NEI)
Bethesda, Maryland, 20892
About this study
Official title: Pilot Study of Leflunomide for the Treatment of Uveitis
This study will investigate the safety and effectiveness of the drug Leflunomide to treat uveitis-an inflammation of the eye caused by an immune system abnormality. Leflunomide suppresses immune system activity and has been shown to control autoimmune diseases, such as arthritis (joint inflammation), in animals. It has also improved symptoms in patients with rheumatoid arthritis, and the Food and Drug Administration has approved it for treating patients with this disease. Eye and joint inflammation may have similar causes, and medicines for arthritis often help patients with eye inflammation. This study will examine whether Leflunomide can help patients with uveitis.
Patients with uveitis who are not responding well to steroid treatment and patients who have side effects from other medicines used to treat uveitis (such as cyclosporine, cyclophosphamide, methotrexate or azathioprine) or have refused treatment because of possible side effects of these medicines may be eligible for this study. Candidates will be screened with a medical history, physical examination, blood test and eye examination. The eye exam includes a check of vision and eye pressure, examination of the back of the eye (retina) with an ophthalmoscope and the front of the eye with a microscope. They will also undergo a procedure called fluorescein angiography to look at the blood vessels of the eye. A dye called sodium fluorescein is injected into the bloodstream through a vein. After the dye reaches the blood vessels of the eye, photographs are taken of the retina.
Study participants will be divided into two groups. One group will take 100 milligrams of Leflunomide once a day for 3 days and then 20 milligrams once a day for 6 months. The other group will take a placebo-a pill that looks like the Leflunomide pill but does not contain the medicine. All patients in both groups will also take prednisone. Patients will have follow-up examinations at weeks 1, 4, 8, 12, 16, and 24 (6 months) of the study. Each follow-up visit will include a repeat of the screening exams and an evaluation of side effects or discomfort from the medicine. Those who do well and want to continue their assigned treatment after 6 months can continue that treatment for another 6 months and will have follow-up exams at months 9 and 12.
Read the detailed description
Although corticosteroids remain the mainstay of therapy for intraocular inflammation, many patients are intolerant or resistant to corticosteroid therapy. In these patients, other immunosuppressive agents have been employed to control potentially sight-threatening uveitis. Nevertheless, ideal therapy for these patients remains elusive, and there is a need for new immunosuppressive agents with varying modes of action and side effect profiles. Leflunomide, an isoxazole derivative, has profound immunosuppressive activity. Leflunomide inhibits autoimmune disease in animal models and has been used to treat patients with rheumatoid arthritis (RA). We propose a randomized masked pilot trial of leflunomide versus placebo for the treatment of uveitis. Sixteen patients 16 years of age or older with active intermediate, posterior, or panuveitis will be randomly assigned to receive prednisone and leflunomide or prednisone and placebo. Patients will then have the prednisone tapered according to a standardized schedule. The primary purpose of the study is to investigate the safety and efficacy of leflunomide versus placebo. The primary safety endpoint is the frequency of any of the following: abdominal pain, diarrhea, skin rash, hypertension, and alopecia. In addition, weight loss distributions and change in liver function tests will be described. The primary efficacy endpoint is any one or more of the following (1) a decrease of 10 or more letters in visual acuity from the baseline score for any reason, or (2) inability to taper prednisone to 10 mg qd by week 16 post randomization, or (3) inability to maintain the prednisone taper through Month 6 or Month 12, or (4) the addition of systemic therapy to treat ocular inflammatory disease. Secondary outcomes will include change in vitreous haze and presence or absence of cystoid macular edema.
- Conditions
- Uveitis
- Being tested
- Leflunomide
- Keywords
- Immunosuppression, Inflammation, Eye, Vision, Medication, Uveitis, Leflunomide, Vitritis
- Medical subject headings
- Uveitis, Inflammation, Uveitis, Intermediate
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LeflunomideDrug
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Nov 1999 (estimated)
- Study startMar 1999
- Study completionFeb 2003
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for UveitisStudies 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 2
- Primary purpose
- Treatment
- Enrolment
- 16 participants
Sponsor and investigators
- Lead sponsor
- National Eye Institute (NEI)
- Sponsor type
- US National Institutes of Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00001863
- Sponsor's protocol ID
- 990059
- Other IDs
- 99-EI-0059
- Status last verified
- Feb 2003
- First submitted
- 3 Nov 1999
- Last updated
- 4 Mar 2008
- Results posted
- No
Publications
Whitcup SM, Nussenblatt RB. Treatment of autoimmune uveitis. Ann N Y Acad Sci. 1993 Nov 30;696:307-18. doi: 10.1111/j.1749-6632.1993.tb17166.x.
PubMed 8109836Whitcup SM, Salvo EC Jr, Nussenblatt RB. Combined cyclosporine and corticosteroid therapy for sight-threatening uveitis in Behcet's disease. Am J Ophthalmol. 1994 Jul 15;118(1):39-45. doi: 10.1016/s0002-9394(14)72840-5.
PubMed 8023874Nussenblatt RB, Palestine AG, Chan CC. Cyclosporin A therapy in the treatment of intraocular inflammatory disease resistant to systemic corticosteroids and cytotoxic agents. Am J Ophthalmol. 1983 Sep;96(3):275-82. doi: 10.1016/s0002-9394(14)77814-6.
PubMed 6614105
Study at a glance
From the registry record, last updated by the sponsor on 4 Mar 2008. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pilot Study of Leflunomide for the Treatment of Uveitis
- ClinicalTrials.gov ID
- NCT00001863
- Acronym / sponsor ID
- 990059
- Conditions
- Uveitis
- Keywords
- Immunosuppression, Inflammation, Eye, Vision, Medication, Uveitis, Leflunomide, Vitritis
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 16 participants
- Lead sponsor
- National Eye Institute (NEI)US National Institutes of Health
- Study start
- Mar 1999
- Study completion
- Feb 2003
- First posted
- 4 Nov 1999 (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 will investigate the safety and effectiveness of the drug Leflunomide to treat uveitis-an inflammation of the eye caused by an immune system abnormality. Leflunomide suppresses immune system activity and has been shown to control autoimmune diseases, such as arthritis (joint inflammation), in animals. It has also improved symptoms in patients with rheumatoid arthritis, and the Food and Drug Administration has approved it for treating patients with this disease. Eye and joint inflammation may have similar causes, and medicines for arthritis often help patients with eye inflammation. This study will examine whether Leflunomide can help patients with uveitis.
Patients with uveitis who are not responding well to steroid treatment and patients who have side effects from other medicines used to treat uveitis (such as cyclosporine, cyclophosphamide, methotrexate or azathioprine) or have refused treatment because of possible side effects of these medicines may be eligible for this study. Candidates will be screened with a medical history, physical examination, blood test and eye examination. The eye exam includes a check of vision and eye pressure, examination of the back of the eye (retina) with an ophthalmoscope and the front of the eye with a microscope. They will also undergo a procedure called fluorescein angiography to look at the blood vessels of the eye. A dye called sodium fluorescein is injected into the bloodstream through a vein. After the dye reaches the blood vessels of the eye, photographs are taken of the retina.
Study participants will be divided into two groups. One group will take 100 milligrams of Leflunomide once a day for 3 days and then 20 milligrams once a day for 6 months. The other group will take a placebo-a pill that looks like the Leflunomide pill but does not contain the medicine. All patients in both groups will also take prednisone. Patients will have follow-up examinations at weeks 1, 4, 8, 12, 16, and 24 (6 months) of the study. Each follow-up visit will include a repeat of the screening exams and an evaluation of side effects or discomfort from the medicine. Those who do well and want to continue their assigned treatment after 6 months can continue that treatment for another 6 months and will have follow-up exams at months 9 and 12.
Detailed description
Although corticosteroids remain the mainstay of therapy for intraocular inflammation, many patients are intolerant or resistant to corticosteroid therapy. In these patients, other immunosuppressive agents have been employed to control potentially sight-threatening uveitis. Nevertheless, ideal therapy for these patients remains elusive, and there is a need for new immunosuppressive agents with varying modes of action and side effect profiles. Leflunomide, an isoxazole derivative, has profound immunosuppressive activity. Leflunomide inhibits autoimmune disease in animal models and has been used to treat patients with rheumatoid arthritis (RA). We propose a randomized masked pilot trial of leflunomide versus placebo for the treatment of uveitis. Sixteen patients 16 years of age or older with active intermediate, posterior, or panuveitis will be randomly assigned to receive prednisone and leflunomide or prednisone and placebo. Patients will then have the prednisone tapered according to a standardized schedule. The primary purpose of the study is to investigate the safety and efficacy of leflunomide versus placebo. The primary safety endpoint is the frequency of any of the following: abdominal pain, diarrhea, skin rash, hypertension, and alopecia. In addition, weight loss distributions and change in liver function tests will be described. The primary efficacy endpoint is any one or more of the following (1) a decrease of 10 or more letters in visual acuity from the baseline score for any reason, or (2) inability to taper prednisone to 10 mg qd by week 16 post randomization, or (3) inability to maintain the prednisone taper through Month 6 or Month 12, or (4) the addition of systemic therapy to treat ocular inflammatory disease. Secondary outcomes will include change in vitreous haze and presence or absence of cystoid macular edema.
Study design
- Primary purpose
- Treatment
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (6 listed)
- Diagnosis of current intermediate or posterior uveitis, or panuveitis.
- Current evidence of active intraocular inflammation based on the presence of vitreous haze, active retinal lesions, retinal vasculitis, or cystoid macular edema.
- 16 years of age or older.
- Visual acuity of 73 letters or fewer (Snellen equivalent: 20/40 or worse) in at least one eye.
- The ability to understand and sign an informed consent form which must be obtained prior to randomization.
Key exclusion criteria (11 listed)
- Ocular or systemic disease requiring greater than 1 mg/kg/day of prednisone or greater than 80 mg qd if patients weigh more than 80 kg, or requiring other systemic immunosuppressants.
- Periocular injections of corticosteroids within the previous 4 weeks.
- Intolerance or contraindications to corticosteroids.
- Female who is pregnant or lactating.
- Patient refuses to use contraception during the study and 24 months after termination of active study therapy or undergo a cholestyramine washout regimen or an activated charcoal regimen under the care of a physician following termination of study therapy, if child-bearing or fathering potential exists.
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 |
|---|---|---|
| Leflunomide | Drug | – |
Primary outcome
Not reported in the source record.
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 4 Mar 2008.
- Background: PubMed 8109836Whitcup SM, Nussenblatt RB. Treatment of autoimmune uveitis. Ann N Y Acad Sci. 1993 Nov 30;696:307-18. doi: 10.1111/j.1749-6632.1993.tb17166.x.
- Background: PubMed 8023874Whitcup SM, Salvo EC Jr, Nussenblatt RB. Combined cyclosporine and corticosteroid therapy for sight-threatening uveitis in Behcet's disease. Am J Ophthalmol. 1994 Jul 15;118(1):39-45. doi: 10.1016/s0002-9394(14)72840-5.
- Background: PubMed 6614105Nussenblatt RB, Palestine AG, Chan CC. Cyclosporin A therapy in the treatment of intraocular inflammatory disease resistant to systemic corticosteroids and cytotoxic agents. Am J Ophthalmol. 1983 Sep;96(3):275-82. doi: 10.1016/s0002-9394(14)77814-6.
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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.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Leflunomide in people with Uveitis, run by National Eye Institute (NEI) 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 6 inclusion and 11 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 4 Mar 2008. 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 phase mean?
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.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00001863, which also lists 3 linked publications.
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 4 Mar 2008.