First-line Antimetabolites as Steroid-sparing Treatment Uveitis Pilot Trial

NCT01232920 | Completed Phase 3 Results DMC

• 1 other identifier: 10-00235
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 2

Brief Summary

The proposed study is a masked trial, with stratified block randomization by site, designed to determine which treatment, methotrexate or mycophenolate mofetil, is more effective as first-line steroid-sparing treatment for patients with non-infectious uveitis requiring corticosteroid-sparing therapy. One hundred non-infectious uveitis patients in need of corticosteroid-sparing therapy will be randomized to receive either oral methotrexate or oral mycophenolate mofetil at Aravind Eye Hospitals (Madurai and Coimbatore, South India). They will be followed monthly for 6 months after enrollment or until treatment failure. The investigators hypothesize that the proportion achieving corticosteroid-sparing success at 6 months for patients taking mycophenolate mofetil will be improved in comparison with patients taking methotrexate.

Conditions

Uveitis

Keywords

uveitis; antimetabolite; immunosuppressive; clinical trial

Outcome Measures

Primary Outcomes (1)

• Number of Participants Achieving Treatment Success

  TREATMENT SUCCESS is defined as controlled ocular inflammation in both eyes with less than or equal to 10 mg/day of prednisone and/or 2 topical steroid drops/day sustained for 2 visits separated by at least 28 days (control of inflammation and prednisone dose must be achieved by 5-month visit and sustained until 6-month visit). Discontinuation of study medication at any time due to efficacy, tolerability, or safety may result in a declaration of TREATMENT FAILURE. Note that all patients will be classified as either a treatment success or failure.

  6 months

Secondary Outcomes (3)

• Time to Control of Inflammation

  6 months

• Change in Best Spectacle-corrected Visual Acuity (BSCVA)

  6 months

• Number of Eyes With Resolution of Macular Edema

  6 months

Study Arms (2)

Methotrexate

ACTIVE COMPARATOR

Drug: Methotrexate

Mycophenolate mofetil

ACTIVE COMPARATOR

Drug: Mycophenolate mofetil

Interventions

Methotrexate DRUG

All methotrexate doses will be taken orally once per week in a divided dose (half in the morning, half in the evening), and should be taken with food. For the first two weeks, a loading dose of 15 mg/week orally will be administered to assess tolerability. After two weeks, the dose will be ramped up to 25 mg/week until the end of follow-up or until treatment failure due to intolerability, adverse events, or of lack of efficacy. If the study ophthalmologist decides to reduce the study treatment dose due to intolerability, the dose will be reduced to 20 mg per week while maintaining masking. If side effects persist and the study ophthalmologist wishes to reduce the dose a second time, the dose will be reduced to 15 mg per week.

Methotrexate

Mycophenolate mofetil DRUG

Mycophenolate mofetil will be taken twice daily on an empty stomach. For the first two weeks, a loading dose of 500 mg/BID orally will be administered to assess tolerability. After two weeks, the dose will be ramped up to 1 g/BID until the end of follow-up or until treatment failure due to intolerability, adverse events, or lack of efficacy. If the study ophthalmologist decides to reduce the study treatment dose due to intolerability, the dose will be reduced to 750 mg/BID while maintaining masking. If side effects persist and the study ophthalmologist wishes to reduce the dose a second time, the dose will be reduced to 500 mg/BID.

Also known as: Cellcept

Mycophenolate mofetil

Eligibility Criteria

• Age: 16 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Non-infectious anterior, intermediate, posterior or panuveitis
• Active uveitis within the last 60 days (defined by the presence of any of the following according to SUN criteria: ≥ 1+ anterior chamber cells, anterior vitreous cells, vitreous haze, active retinal or choroidal lesions)
• Prednisone dose ≥ 15 mg/day
• History of corticosteroid taper failure (inability to taper to prednisone 10 mg or less) or obvious chronic disease necessitating corticosteroid-sparing immunosuppressive treatment

You may not qualify if:

• Any infectious cause of uveitis
• Tuberculosis: Evidence of active TB (PPD and CXR required - latent TB patients are still eligible)
• Positive for Hepatitis: HBsAg and/or Hep C antibody
• Positive for Syphilis: RPR/VDRL and/or FTA-ABS
• Abnormal CBC (\<2500 WBC or \<75,000 Plts or \<10 Hgb)
• Abnormal liver and/or kidney tests (ALT/AST \>2x normal or CR\>1.5)
• Pregnancy or breast-feeding (blood or urine pregnancy test for all females, excluding those who are post-menopausal)
• Chronic hypotony (IOP \< 5 mm Hg for \> 3 months)
• Prior use of any immunosuppressive drug for the treatment of uveitis in the past 6 months
• Prior failed treatment with methotrexate or mycophenolate mofetil
• Periocular or intravitreal corticosteroid injection in the past 3 months
• Fluocinolone acetonide implant surgery in either eye in \< 3 years
• Intraocular surgery in \< 30 days, or any ocular surgery scheduled during the 6-month study period
• VA of hand motions or worse in better eye
• \< 16 years of age at enrollment

Sponsors & Collaborators

• University of California, San Francisco: lead
• Aravind Eye Hospitals, India: collaborator

Study Sites (2)

Aravind Eye Hospital

Coimbatore, Tamil Nadu, India

Location

Aravind Eye Hospital

Madurai, Tamil Nadu, India

Location

Related Publications (1)

• Niemeyer KM, Gonzales JA, Rathinam SR, Babu M, Thundikandy R, Kanakath A, Porco TC, Browne EN, Rao MM, Acharya NR. Quality-of-Life Outcomes From a Randomized Clinical Trial Comparing Antimetabolites for Intermediate, Posterior, and Panuveitis. Am J Ophthalmol. 2017 Jul;179:10-17. doi: 10.1016/j.ajo.2017.04.003. Epub 2017 Apr 14.

  PMID: 28414043 DERIVED

MeSH Terms

Conditions

Uveitis

Interventions

Methotrexate; Mycophenolic Acid

Condition Hierarchy (Ancestors)

Uveal Diseases; Eye Diseases

Intervention Hierarchy (Ancestors)

Aminopterin; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Caproates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Fatty Acids; Lipids

Results Point of Contact

• Title: Nisha Acharya
• Organization: Proctor Foundation, University of California San Francisco

nisha.acharya@ucsf.edu

415-476-8131

Study Officials

• S R Rathinam, MD

  Aravind Eye Hospital

  PRINCIPAL INVESTIGATOR

• M B Babu, MD

  Aravind Eye Hospital

  PRINCIPAL INVESTIGATOR

• Nisha Acharya, MD MS

  Proctor Foundation, UCSF

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 1, 2010
• First Posted: November 2, 2010
• Study Start: October 1, 2010
• Primary Completion: June 1, 2012
• Study Completion: June 1, 2012
• Last Updated: July 15, 2016
• Results First Posted: January 5, 2016

Record last verified: 2016-06

Locations

IN (2)