Trial Review

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT01829295




Registration number
NCT01829295
Ethics application status
Date submitted
8/04/2013
Date registered
11/04/2013
Date last updated
2/04/2024

Titles & IDs
Public title
Methotrexate and Mycophenolate Mofetil for UVEITIS
Scientific title
First-line Antimetabolites as Steroid-sparing Treatment (FAST) Uveitis Trial
Secondary ID [1] 0 0
5U10EY021125
Secondary ID [2] 0 0
11-08227
Universal Trial Number (UTN)
Trial acronym
FAST
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Uveitis 0 0
Condition category
Condition code
Inflammatory and Immune System 0 0 0 0
Other inflammatory or immune system disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Mycophenolate mofetil
Treatment: Drugs - Methotrexate
Treatment: Drugs - Prednisone

Experimental: Methotrexate - oral methotrexate

Experimental: Mycophenolate Mofetil - oral mycophenolate mofetil


Treatment: Drugs: 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.

Treatment: Drugs: 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)

Treatment: Drugs: 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.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Number of Participants Achieving Treatment Success at 6 Months (Phase I, 0-6 Months)
Timepoint [1] 0 0
6 Months
Secondary outcome [1] 0 0
Number of Participants Achieving Treatment Success at 12 Months on Same Medication (Phase I, 6-12 Months)
Timepoint [1] 0 0
12 Months
Secondary outcome [2] 0 0
Number of Participants Achieving Treatment Success After Switching to Other Medication (Phase II, 0-6 Months)
Timepoint [2] 0 0
6 Months

Eligibility
Key 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.

-
Minimum age
16 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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 design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?


The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Crossover
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/08/2013
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
9/08/2018
Sample size
Target
Accrual to date
Final
216
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 0 0
Royal Victorian Eye and Ear Hospital - Melbourne
Recruitment postcode(s) [1] 0 0
3002 - Melbourne
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Illinois
Country [3] 0 0
United States of America
State/province [3] 0 0
Oregon
Country [4] 0 0
India
State/province [4] 0 0
Tamil Nadu
Country [5] 0 0
Mexico
State/province [5] 0 0
Mexico, D.F.
Country [6] 0 0
Saudi Arabia
State/province [6] 0 0
Riyadh

Funding & Sponsors
Primary sponsor type
Other
Name
University of California, San Francisco
Address
Country
Other collaborator category [1] 0 0
Other
Name [1] 0 0
Aravind Eye Hospitals, India
Address [1] 0 0
Country [1] 0 0
Other collaborator category [2] 0 0
Other
Name [2] 0 0
Oregon Health and Science University
Address [2] 0 0
Country [2] 0 0
Other collaborator category [3] 0 0
Other
Name [3] 0 0
Asociación para Evitar la Ceguera en México
Address [3] 0 0
Country [3] 0 0
Other collaborator category [4] 0 0
Other
Name [4] 0 0
Royal Victoria Eye and Ear Hospital
Address [4] 0 0
Country [4] 0 0
Other collaborator category [5] 0 0
Other
Name [5] 0 0
Northwestern University
Address [5] 0 0
Country [5] 0 0
Other collaborator category [6] 0 0
Government body
Name [6] 0 0
National Eye Institute (NEI)
Address [6] 0 0
Country [6] 0 0
Other collaborator category [7] 0 0
Other
Name [7] 0 0
King Khaled Eye Specialist Hospital
Address [7] 0 0
Country [7] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
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.
Trial website
https://clinicaltrials.gov/ct2/show/NCT01829295
Trial related presentations / publications
Galor A, Jabs DA, Leder HA, Kedhar SR, Dunn JP, Peters GB 3rd, Thorne JE. Comparison of antimetabolite drugs as corticosteroid-sparing therapy for noninfectious ocular inflammation. Ophthalmology. 2008 Oct;115(10):1826-32. doi: 10.1016/j.ophtha.2008.04.026. Epub 2008 Jun 25.
Siepmann K, Huber M, Stubiger N, Deuter C, Zierhut M. Mycophenolate mofetil is a highly effective and safe immunosuppressive agent for the treatment of uveitis : a retrospective analysis of 106 patients. Graefes Arch Clin Exp Ophthalmol. 2006 Jul;244(7):788-94. doi: 10.1007/s00417-005-0066-8. Epub 2005 Sep 15.
Teoh SC, Hogan AC, Dick AD, Lee RW. Mycophenolate mofetil for the treatment of uveitis. Am J Ophthalmol. 2008 Nov;146(5):752-60, 760.e1-3. doi: 10.1016/j.ajo.2008.03.004. Epub 2008 May 2.
Thorne JE, Jabs DA, Qazi FA, Nguyen QD, Kempen JH, Dunn JP. Mycophenolate mofetil therapy for inflammatory eye disease. Ophthalmology. 2005 Aug;112(8):1472-7. doi: 10.1016/j.ophtha.2005.02.020.
Larkin G, Lightman S. Mycophenolate mofetil. A useful immunosuppressive in inflammatory eye disease. Ophthalmology. 1999 Feb;106(2):370-4. doi: 10.1016/S0161-6420(99)90078-7.
Baltatzis S, Tufail F, Yu EN, Vredeveld CM, Foster CS. Mycophenolate mofetil as an immunomodulatory agent in the treatment of chronic ocular inflammatory disorders. Ophthalmology. 2003 May;110(5):1061-5. doi: 10.1016/S0161-6420(03)00092-7.
Choudhary A, Harding SP, Bucknall RC, Pearce IA. Mycophenolate mofetil as an immunosuppressive agent in refractory inflammatory eye disease. J Ocul Pharmacol Ther. 2006 Jun;22(3):168-75. doi: 10.1089/jop.2006.22.168.
Bom S, Zamiri P, Lightman S. Use of methotrexate in the management of sight-threatening uveitis. Ocul Immunol Inflamm. 2001 Mar;9(1):35-40. doi: 10.1076/ocii.9.1.35.3983.
Dev S, McCallum RM, Jaffe GJ. Methotrexate treatment for sarcoid-associated panuveitis. Ophthalmology. 1999 Jan;106(1):111-8. doi: 10.1016/S0161-6420(99)90011-8.
Foeldvari I, Wierk A. Methotrexate is an effective treatment for chronic uveitis associated with juvenile idiopathic arthritis. J Rheumatol. 2005 Feb;32(2):362-5.
Gangaputra S, Newcomb CW, Liesegang TL, Kacmaz RO, Jabs DA, Levy-Clarke GA, Nussenblatt RB, Rosenbaum JT, Suhler EB, Thorne JE, Foster CS, Kempen JH; Systemic Immunosuppressive Therapy for Eye Diseases Cohort Study. Methotrexate for ocular inflammatory diseases. Ophthalmology. 2009 Nov;116(11):2188-98.e1. doi: 10.1016/j.ophtha.2009.04.020. Epub 2009 Sep 12.
Holz FG, Krastel H, Breitbart A, Schwarz-Eywill M, Pezzutto A, Volcker HE. Low-dose methotrexate treatment in noninfectious uveitis resistant to corticosteroids. Ger J Ophthalmol. 1992;1(3-4):142-4.
Shah SS, Lowder CY, Schmitt MA, Wilke WS, Kosmorsky GS, Meisler DM. Low-dose methotrexate therapy for ocular inflammatory disease. Ophthalmology. 1992 Sep;99(9):1419-23. doi: 10.1016/s0161-6420(92)31790-7.
Taylor SR, Habot-Wilner Z, Pacheco P, Lightman SL. Intraocular methotrexate in the treatment of uveitis and uveitic cystoid macular edema. Ophthalmology. 2009 Apr;116(4):797-801. doi: 10.1016/j.ophtha.2008.10.033.
Daniel E, Thorne JE, Newcomb CW, Pujari SS, Kacmaz RO, Levy-Clarke GA, Nussenblatt RB, Rosenbaum JT, Suhler EB, Foster CS, Jabs DA, Kempen JH. Mycophenolate mofetil for ocular inflammation. Am J Ophthalmol. 2010 Mar;149(3):423-32.e1-2. doi: 10.1016/j.ajo.2009.09.026. Epub 2009 Dec 30.
Sobrin L, Christen W, Foster CS. Mycophenolate mofetil after methotrexate failure or intolerance in the treatment of scleritis and uveitis. Ophthalmology. 2008 Aug;115(8):1416-21, 1421.e1. doi: 10.1016/j.ophtha.2007.12.011. Epub 2008 Jan 25.
Jabs DA, Nussenblatt RB, Rosenbaum JT; Standardization of Uveitis Nomenclature (SUN) Working Group. Standardization of uveitis nomenclature for reporting clinical data. Results of the First International Workshop. Am J Ophthalmol. 2005 Sep;140(3):509-16. doi: 10.1016/j.ajo.2005.03.057.
Jabs DA, Rosenbaum JT, Foster CS, Holland GN, Jaffe GJ, Louie JS, Nussenblatt RB, Stiehm ER, Tessler H, Van Gelder RN, Whitcup SM, Yocum D. Guidelines for the use of immunosuppressive drugs in patients with ocular inflammatory disorders: recommendations of an expert panel. Am J Ophthalmol. 2000 Oct;130(4):492-513. doi: 10.1016/s0002-9394(00)00659-0.
Public notes

Contacts
Principal investigator
Name 0 0
Nisha Acharya, MD, MS
Address 0 0
University of California, San Francisco
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT01829295