Treatment of Non-infectious Intermediate and Posterior Uveitis Associated Macular Edema With Intravitreal Methotrexate

NCT01314417 | Terminated Phase 1 Results

• 2 other identifiers: 11010711-EI-0107
• Study Type: interventional
• Target: 2
• Locations: 1 country
• Sites: 1

Brief Summary

BACKGROUND: Uveitis comprises of a group of diseases associated with inflammation of the eye that can lead to vision loss. Some people with uveitis also have macular edema (swelling of the retina at the back of the eye). Uveitis and macular edema are treated with medications and sometimes surgery, but treatment does not always prevent vision loss. Previous research has shown that injections of methotrexate into the eye of people with eye disease other than uveitis can help relieve the inflammation, or swelling, that causes macular edema and can slow visual loss. However, it has not yet been approved as a treatment for macular edema associated with uveitis. OBJECTIVES: To evaluate the safety and effectiveness of methotrexate injections as a treatment for macular edema associated with uveitis. ELIGIBILITY: Individuals at least 18 years of age who have been diagnosed with uveitis and macular edema in at least one eye. DESIGN:

• This study requires at least nine visits to the National Eye Institute study clinic over a period of 6 months (24 weeks).
• Participants will be screened with a physical and ophthalmic examination, medical history, blood and urine tests, and additional eye and other tests as needed.
• Participants will receive a methotrexate injection in a selected treatment eye. After the injection, participants will receive antibiotic eye drops to place in the eye three times a day for the 3 days following the injection, leucovorin (folic acid) drops to place in the eye four times a day for 1 week following the injection, and a dose of folic acid to be taken by mouth the day after the injection.
• Participants who tolerate the initial injection may continue to receive injections in their study eye every month for 6 months. After 6 months, participants who show improvement from the injections may be evaluated to receive additional injections every 4 to 8 weeks until researchers end the study.

Conditions

Non-infectious Intermediate and Posterior Uveitis

Keywords

Uveitis; Macular Edema; Methotrexate

Outcome Measures

Primary Outcomes (1)

• Number of Participants Who Meet the Definition of Treatment Success Within 12 Weeks From Baseline.

  Treatment success is defined as achieving at least a 1-step decrease in the LogScore scale for central macular thickness. A decrease of at least 1-step on the logOCT scale, where Change in logOCT=log(follow-up thickness/200) - log(baseline thickness/200) is considered clinically significant. A 1-step decrease is equivalent to at least a 20% improvement of central macular thickness and represents greater than twice the variability of retinal thickness measurements (approximately 25-30 µ). Examples of OCT measurements with their corresponding LogScore, where LogScore=10xlogOCT are as follows: LogScore 0 = OCT 200 µm, LogScore 1 = OCT 250 µm, LogScore 2 = OCT 320 µm, LogScore 3 = OCT 400 µm, LogScore 4 = OCT 500 µm, LogScore 5 = OCT 640 µm, LogScore 6 = OCT 800 µm, LogScore 7 = OCT 1000 µm

  12 weeks

Secondary Outcomes (25)

• Change in Optical Coherence Tomography (OCT) Excess Retinal Thickening in the Study Eye at 4 Weeks Compared to Baseline

  Baseline and Week 4

• Change in Optical Coherence Tomography (OCT) Excess Retinal Thickening in the Study Eye at 8 Weeks Compared to Baseline

  Baseline and Week 8

• Change in Optical Coherence Tomography (OCT) Excess Retinal Thickening in the Study Eye at 12 Weeks Compared to Baseline

  Baseline and Week 12

• Change in Optical Coherence Tomography (OCT) Excess Retinal Thickening in the Study Eye at 16 Weeks Compared to Baseline

  Baseline and Week 16

• Change in Optical Coherence Tomography (OCT) Excess Retinal Thickening in the Study Eye at 20 Weeks Compared to Baseline

  Baseline and Week 20

Study Arms (1)

Methotrexate

EXPERIMENTAL

400 μg/100 μL injection

Drug: Methotrexate

Interventions

Methotrexate DRUG

400 μg/100 μL monthly injections for the first 3 months, then as needed per the treatment criteria

Methotrexate

Eligibility Criteria

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

You may qualify if:

• Participant must be 18 years of age or older.
• Participant must understand and sign the protocol's informed consent document.
• Participant is willing to comply with the study procedures and return for all study visits.
• Participant has chronic macular edema secondary to non-infectious panuveitis, posterior or intermediate uveitis in at least one eye (the study eye) that has:
• not been responsive to conventional immunosuppressive therapy in the past 3 months; OR
• recurred while on conventional immunosuppressive therapy.
• Participant has central macular thickness of ≥ 270 microns in the study eye.
• Participant has visual acuity of 20/400 or better (≥ 19 ETDRS letters) in the study eye.
• Female participants of childbearing potential must not be pregnant or breast-feeding, must have a negative serum pregnancy test at screening and must be willing to undergo serum pregnancy tests throughout the study.
• Both female participants of childbearing potential (see Appendix 1 for definition) and male participants able to father children must have (or have a partner who has) had a hysterectomy or vasectomy, be completely abstinent from intercourse or must agree to practice two acceptable methods of contraception throughout the course of the study and for six months after the last study medication injection. Acceptable methods of contraception include:
• hormonal contraception (i.e., birth control pills, injected hormones, dermal patch or vaginal ring),
• intrauterine device,
• barrier methods (diaphragm, condom) with spermicide, or
• surgical sterilization (tubal ligation).

You may not qualify if:

• Participant is in another investigational study and actively receiving investigational therapy for macular edema.
• Participant has evidence of infectious panuveitis, posterior or intermediate uveitis in either eye.
• Participant is expected to need ocular surgery in the study eye during the course of the trial.
• Participant had intraocular surgery in the study eye within the past 90 days.
• Participant had an injection of bevacizumab or ranibizumab within the past four weeks in the study eye.
• Participant had an injection of triamcinolone within the past six weeks in the study eye.
• Participant has a systemic condition that, in the opinion of the investigator, would preclude participation in the study.
• Participant has significant cataract or media opacity in the study eye that makes posterior segment visualization difficult as determined by investigator.
• Participant has a confirmed positive serologic and/or molecular test for HIV-1/2.

Sponsors & Collaborators

• National Eye Institute (NEI): lead

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (4)

• Lardenoye CW, van Kooij B, Rothova A. Impact of macular edema on visual acuity in uveitis. Ophthalmology. 2006 Aug;113(8):1446-9. doi: 10.1016/j.ophtha.2006.03.027.

  PMID: 16877081 BACKGROUND

• Kiss CG, Barisani-Asenbauer T, Maca S, Richter-Mueksch S, Radner W. Reading performance of patients with uveitis-associated cystoid macular edema. Am J Ophthalmol. 2006 Oct;142(4):620-4. doi: 10.1016/j.ajo.2006.05.001.

  PMID: 17011854 BACKGROUND

• Rothova A. Inflammatory cystoid macular edema. Curr Opin Ophthalmol. 2007 Nov;18(6):487-92. doi: 10.1097/ICU.0b013e3282f03d2e.

  PMID: 18163001 BACKGROUND

• van Kooij B, Rothova A, de Vries P. The pros and cons of intravitreal triamcinolone injections for uveitis and inflammatory cystoid macular edema. Ocul Immunol Inflamm. 2006 Apr;14(2):73-85. doi: 10.1080/09273940500545684.

  PMID: 16597536 BACKGROUND

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Uveitis, Posterior; Uveitis; Macular Edema

Interventions

Methotrexate

Condition Hierarchy (Ancestors)

Panuveitis; Uveal Diseases; Eye Diseases; Macular Degeneration; Retinal Degeneration; Retinal Diseases

Intervention Hierarchy (Ancestors)

Aminopterin; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: H. Nida Sen, MD, MHSc, Principal Investigator, NEI
• Organization: National Institutes of Health

senh@nei.nih.gov

301-402-3254

Study Officials

• Hatice N Sen, M.D.

  National Eye Institute (NEI)

  PRINCIPAL INVESTIGATOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: March 11, 2011
• First Posted: March 14, 2011
• Study Start: February 1, 2011
• Primary Completion: January 1, 2013
• Study Completion: January 1, 2013
• Last Updated: March 27, 2019
• Results First Posted: September 26, 2013

Record last verified: 2018-07

Locations

US (1)