Methotrexate and Mycophenolate Mofetil for UVEITIS (FAST)
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| ClinicalTrials.gov Identifier: NCT01829295 |
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Recruitment Status :
Completed
First Posted : April 11, 2013
Results First Posted : April 26, 2019
Last Update Posted : November 6, 2019
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| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Uveitis | Drug: Mycophenolate mofetil Drug: Methotrexate Drug: Prednisone | Phase 3 |
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 216 participants |
| Allocation: | Randomized |
| Intervention Model: | Crossover Assignment |
| Masking: | Double (Investigator, Outcomes Assessor) |
| Primary Purpose: | Treatment |
| Official Title: | First-line Antimetabolites as Steroid-sparing Treatment (FAST) Uveitis Trial |
| Study Start Date : | August 2013 |
| Actual Primary Completion Date : | February 21, 2018 |
| Actual Study Completion Date : | August 9, 2018 |
| Arm | Intervention/treatment |
|---|---|
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Experimental: Methotrexate
oral methotrexate
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Drug: Methotrexate
For the first two weeks, an introductory dose of 15 mg/week (7.5mg BID once a week) orally. After two weeks, the dose will be increased to 25 mg/week (12.5mg BID once a week) Drug: Prednisone All patients enrolled in the study will be initially taking concomitant oral corticosteroids at 1 mg/kg or 60 mg daily, whichever is less. Initial corticosteroid dose will be continued for 2 to 4 weeks at which point prednisone will be gradually tapered. Prednisone will be tapered to and held at 7.5 mg/day for the first 6 months of the study. |
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Experimental: Mycophenolate Mofetil
oral mycophenolate mofetil
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Drug: Mycophenolate mofetil
For the first two weeks, an introductory dose of 500 mg BID orally. After two weeks, the dose will be increased to 1.5 g BID.
Other Name: Cellcept Drug: Prednisone All patients enrolled in the study will be initially taking concomitant oral corticosteroids at 1 mg/kg or 60 mg daily, whichever is less. Initial corticosteroid dose will be continued for 2 to 4 weeks at which point prednisone will be gradually tapered. Prednisone will be tapered to and held at 7.5 mg/day for the first 6 months of the study. |
- Number of Participants Achieving Treatment Success at 6 Months (Phase I, 0-6 Months) [ Time Frame: 6 Months ]Controlled ocular inflammation (≤ 0.5+ anterior chamber cells, ≤ 0.5+ vitreous haze, no active retinal/choroidal lesions in both eyes) with 7.5 mg/day of oral prednisone and ≤ 2 drops/day of topical 1% prednisolone acetate.
- Number of Participants Achieving Treatment Success at 12 Months on Same Medication (Phase I, 6-12 Months) [ Time Frame: 12 Months ]Controlled ocular inflammation (≤ 0.5+ anterior chamber cells, ≤ 0.5+ vitreous haze, no active retinal/choroidal lesions in both eyes) with 7.5 mg/day of oral prednisone and ≤ 2 drops/day of topical 1% prednisolone acetate in patients who were a treatment success at the primary outcome of 6 months.
- Number of Participants Achieving Treatment Success After Switching to Other Medication (Phase II, 0-6 Months) [ Time Frame: 6 Months ]Controlled ocular inflammation (≤ 0.5+ anterior chamber cells, ≤ 0.5+ vitreous haze, no active retinal/choroidal lesions in both eyes) with 7.5 mg/day of oral prednisone and ≤ 2 drops/day of topical 1% prednisolone acetate for patients who crossed over to other medication following treatment failure at 6 months (or earlier).
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| Ages Eligible for Study: | 16 Years and older (Child, Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- All the following criteria must be met at enrollment:
Historical non-infectious intermediate, anterior and intermediate, posterior or panuveitis in at least one eye
Active inflammation within the last 180 days, defined by the presence of any of the following (in at least one eye) according to SUN criteria:
- ≥ 2+ anterior chamber cells
- ≥ 2+ vitreous haze
- active retinal or choroidal lesions
Active inflammation at enrollment, defined by the presence of any of the following (in at least one eye) according to SUN criteria:
- ≥1+ anterior chamber cells and/or
- ≥1+ vitreous haze and/or
- active retinal/choroidal lesions
At least one of the following criteria must be met before or at enrollment:
- Active inflammation after 4 weeks of high-dose (1mg/kg prednisone equivalent) corticosteroid treatment or 4 weeks following a regional corticosteroid injection
- Treatment with oral corticosteroids resulting in a reduction of inflammation, followed by an increase in inflammation (of at least 1 grade in anterior chamber cells or vitreous haze or a change of non-active to active lesions) when corticosteroid is tapered, in the 180 weeks prior to enrollment
- Active inflammation after long-acting corticosteroid injection 4 weeks to 180 days prior to enrollment
- Active inflammation after treatment with >10mg/day oral prednisone for at least the past 90 days prior to enrollment
- Known chronic condition necessitating corticosteroid-sparing immunosuppressive treatment: Behcet's disease with posterior segment involvement, multifocal choroiditis with panuveitis, serpiginous choroidopathy, birdshot retinochoroidopathy, diffuse retinal vasculitis, Vogt-Koyanagi-Harada with bullous serous retinal detachments and/or choroidal detachments, sympathetic ophthalmia. No prior therapy required for these patients
Willingness to start corticosteroid treatment at 1mg/kg or 60mg a day of prednisone, whichever is less
Willingness to limit alcohol consumption
Willingness to use an acceptable method of contraception during the study period (i.e. pharmacologics, devices, barrier methods) or abstinence.
- Exclusion Criteria: Any of the following
Any infectious cause of uveitis
Prior immunosuppressive therapy other than corticosteroids in the past 12 months
Prior intolerability or safety issues with methotrexate or mycophenolate mofetil
Prior failure to control ocular or other inflammation using methotrexate or mycophenolate mofetil
Prior biologic therapy at any time
Media opacity (such as cataract and/or corneal scar) and/or extensive posterior synechiae such that examination of the posterior segment is not possible in both eyes
Chronic hypotony (IOP < 5 mm Hg for > 3 months) in both eyes
Periocular or intravitreal corticosteroid injection in the past 4 weeks
Fluocinolone acetonide implant in either eye in < 3 years
Intraocular surgery in < 30 days, or planning on getting surgery within the next 6 months
Best spectacle-corrected visual acuity (BSCVA) of hand motions or worse in better eye
< 16 years of age at enrollment
Planning to conceive during the study period, pregnant or breast-feeding (blood or urine pregnancy test for all females, excluding those who are post-menopausal is mandatory)*
Any history of cancer (If a patient has a history of non-melanoma skin cancer they can still be considered for inclusion in this study, provided it is not currently active).
Systemic autoimmune disease anticipated to dictate treatment course
Abnormal Complete blood count (≤ 2,500 white blood cells and/or ≤ 75,000 platelets and/or ≤9 hemoglobin) within 4 weeks prior to enrollment*
Abnormal alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) ≥ 2 times the upper limit of normal for the lab and/or creatinine ≥ 1.5 within 4 weeks prior to enrollment*
Evidence of active tuberculosis, HIV infection, syphilis, or hepatitis B or C (patients must have a tuberculin skin test, or interferon-gamma release assay, a chest radiograph, RPR/VDRL, FTA-ABS, or other treponemal tests, Hepatitis B surface antigen, Hepatitis C antibody tests, and HIV test within 90 days prior to enrollment)**
*Testing required within 4 weeks prior to enrollment; **Testing required within 90 days prior to enrollment.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01829295
| United States, California | |
| Francis I Proctor Foundation | |
| San Francisco, California, United States, 94143 | |
| United States, Illinois | |
| Northwestern University | |
| Chicago, Illinois, United States, 60611 | |
| United States, Oregon | |
| Oregon Health and Science University - Casey Eye Institute | |
| Portland, Oregon, United States, 97239 | |
| Australia, Victoria | |
| Royal Victorian Eye and Ear Hospital | |
| Melbourne, Victoria, Australia, 3002 | |
| India | |
| Aravind Eye Hospital | |
| Coimbatore, Tamil Nadu, India | |
| Aravind Eye Hospital | |
| Madurai, Tamil Nadu, India | |
| Aravind Eye Hospital | |
| Pondicherry, Tamil Nadu, India | |
| Mexico | |
| Asociacion Para Evita La Ceguera en Mexico | |
| Mexico City, Mexico, D.F., Mexico, 04030 | |
| Saudi Arabia | |
| King Khaled Eye Specialist Hospital | |
| Riyadh, Saudi Arabia | |
| Principal Investigator: | Nisha Acharya, MD, MS | University of California, San Francisco |
Documents provided by University of California, San Francisco:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
| Responsible Party: | University of California, San Francisco |
| ClinicalTrials.gov Identifier: | NCT01829295 |
| Other Study ID Numbers: |
11-08227 5U10EY021125 ( U.S. NIH Grant/Contract ) |
| First Posted: | April 11, 2013 Key Record Dates |
| Results First Posted: | April 26, 2019 |
| Last Update Posted: | November 6, 2019 |
| Last Verified: | October 2019 |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
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antimetabolite, noninfectious |
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Uveitis Uveal Diseases Eye Diseases Mycophenolic Acid Prednisone Methotrexate Anti-Inflammatory Agents Glucocorticoids Hormones Hormones, Hormone Substitutes, and Hormone Antagonists Physiological Effects of Drugs Antineoplastic Agents, Hormonal Antineoplastic Agents Abortifacient Agents, Nonsteroidal Abortifacient Agents |
Reproductive Control Agents Antimetabolites, Antineoplastic Antimetabolites Molecular Mechanisms of Pharmacological Action Dermatologic Agents Enzyme Inhibitors Folic Acid Antagonists Immunosuppressive Agents Immunologic Factors Antirheumatic Agents Nucleic Acid Synthesis Inhibitors Antibiotics, Antineoplastic Antibiotics, Antitubercular Antitubercular Agents Anti-Bacterial Agents |