Methotrexate and Mycophenolate Mofetil for UVEITIS (FAST)

March 5, 2024 updated by: University of California, San Francisco

First-line Antimetabolites as Steroid-sparing Treatment (FAST) Uveitis Trial

In the First-line Antimetabolites as Steroid-sparing Treatment (FAST) Uveitis Trial, the investigators propose to establish which immunosuppressive therapy, methotrexate or mycophenolate mofetil, is more effective as a first-line, corticosteroid-sparing agent for the treatment of non-infectious uveitis in a block-randomized, observer-masked, comparative effectiveness trial.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

This is a randomized comparative effectiveness trial to determine which treatment, methotrexate or mycophenolate mofetil, is more effective as first-line corticosteroid-sparing treatment for patients with non-infectious intermediate, posterior and panuveitis requiring corticosteroid-sparing therapy. The primary outcome is treatment success assessed at the 6 month visit (Phase 1, 0-6 months). If patients are a treatment success, they continue on the medication for another 6 months (Phase 1, 6-12 months). Patients who are a treatment failure can crossover to the other medication (Phase 2, 0-6 months).

Study Type

Interventional

Enrollment (Actual)

216

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Australia
    • Victoria
      • Melbourne, Victoria, Australia, 3002
        • Royal Victorian Eye and Ear Hospital
  • India
    • Tamil Nadu
      • Coimbatore, Tamil Nadu, India
        • Aravind Eye Hospital
      • Madurai, Tamil Nadu, India
        • Aravind Eye Hospital
      • Pondicherry, Tamil Nadu, India
        • Aravind Eye Hospital
  • Mexico
    • Mexico, D.F.
      • Mexico City, Mexico, D.F., Mexico, 04030
        • Asociacion Para Evita La Ceguera en Mexico
  • Saudi Arabia
      • Riyadh, Saudi Arabia
        • King Khaled Eye Specialist Hospital
  • United States
    • California
      • San Francisco, California, United States, 94143
        • Francis I Proctor Foundation
    • Illinois
      • Chicago, Illinois, United States, 60611
        • Northwestern University
    • Oregon
      • Portland, Oregon, United States, 97239
        • Oregon Health and Science University - Casey Eye Institute

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

14 years and older (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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 Standardization of Uveitis Nomenclature (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. pharmacologic medications, 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, Rapid plasma reagin / Venereal disease research laboratory test (RPR/VDRL), fluorescent treponemal antibody absorption test (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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Methotrexate
oral methotrexate
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.
Experimental: Mycophenolate Mofetil
oral mycophenolate mofetil
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.
Drug: Mycophenolate mofetil
For the first two weeks, an introductory dose of 500 mg twice a day (BID) orally. After two weeks, the dose will be increased to 1.5 g BID.
Other Names:
  • Cellcept

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
6 Months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
12 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).
6 Months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of California, San Francisco

Collaborators

Northwestern University
National Eye Institute (NEI)
Oregon Health and Science University
Royal Victoria Eye and Ear Hospital
Asociación para Evitar la Ceguera en México
Aravind Eye Hospitals, India
King Khaled Eye Specialist Hospital

Investigators

  • Principal Investigator: Nisha Acharya, MD, MS, University of California, San Francisco

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

August 1, 2013

Primary Completion (Actual)

February 21, 2018

Study Completion (Actual)

August 9, 2018

Study Registration Dates

First Submitted

April 8, 2013

First Submitted That Met QC Criteria

April 10, 2013

First Posted (Estimated)

April 11, 2013

Study Record Updates

Last Update Posted (Actual)

April 2, 2024

Last Update Submitted That Met QC Criteria

March 5, 2024

Last Verified

March 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 11-08227
  • 5U10EY021125 (U.S. NIH Grant/Contract)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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