Clinical trial NCT01376362: Topical Interferon Gamma for Macular Edema Secondary to Uveitis
Official title: The Treatment of Macular Edema Secondary to Uveitis Using Topical Interferon Gamma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Anterior Uveitis
Uveitis
Keywords: Cystoid Macular Edema
Intermediate Uveitis
Uveitis
OCT
Interferon-Gamma (IFN-Gamma)
Lead sponsor: National Institutes of Health Clinical Center (CC)
Sponsor class: NIH
First posted: 2011-06-20
Enrollment: 5
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The objective of this study is to investigate the safety and efficacy of ocular instillations of interferon gamma-1b as a potential treatment for cystoid macular edema (CME) secondary to uveitis.

Detailed description: Objective: Information gathered from NEI laboratories suggests that cystoid macular edema (CME) is caused by the disequilibrium of the JakStat and mTor signal transduction pathways in the retinal pigment epithelium (RPE). We wish to investigate whether stimulating the JakStat pathway with topically applied interferon gamma-1b can be a therapeutic intervention for the treatment of CME secondary to uveitis. The objective of this study is to investigate the safety and efficacy of ocular instillations of interferon gamma-1b as a potential treatment for CME secondary to uveitis.

Study Population: Five participants with CME as evidenced by OCT (\> 275 microns central macular thickness and/or loss of foveal contour) secondary to uveitis will receive topical ocular instillations of interferon gamma-1b. Up to seven participants may be enrolled in order to obtain the five participants to be included in the analysis if participants withdraw prior to receiving interferon gamma-1b.

Design: This Phase I/II, non-randomized, prospective, uncontrolled, single-center study will involve instilling four drops of interferon gamma-1b (approximately 30 μg) topically on the cornea of the study eye four times a day for one week and measuring the potential response with optical coherence tomography (OCT).

Outcome Measures: The primary outcome is the change in excess central macular thickening as measured by OCT in response to interferon gamma-1b. Treatment success is defined as a 25% decrease in excess central macular thickening at Week 1 as compared with baseline. Secondary efficacy outcomes include changes in macular volume as measured by OCT, visual acuity, intraocular pressure and intraocular inflammation as graded upon slit lamp examination. Secondary safety outcomes include ocular surface irritation assessed by fluorescein staining of the cornea and conjunctiva to assess toxicity, the number and severity of systemic and ocular toxicities, the number of adverse events and the proportion of participants with a visual loss of ≥ 15 Early Treatment Diabetic Retinopathy Study (ETDRS) letters.

Eligibility criteria: Inclusion Criteria

1. Participant must be 18 years of age or older.
2. Participant must understand and sign the protocol's informed consent document.
3. Participant has a diagnosis of CME (central thickness of \>275 microns on OCT and/or disruption of foveal contour) secondary to uveitis in at least one eye (the study eye).
4. Participant is willing to comply with the study procedures and is expected to be able to return for all study visits.
5. Participant has visual acuity of 20/400 or better in the study eye.
6. Female participants of childbearing potential must not be pregnant or breast-feeding.
7. Both female participants of childbearing potential and male participants able to father a child must agree to practice two acceptable forms of contraception during the study and for six weeks following the last administration of investigational product. Acceptable methods of contraception include hormonal contraception (i.e., birth control pills, injected hormones dermal patch or vaginal ring), intrauterine device, barrier methods with spermicide (diaphragm with spermicide, condom with spermicide) or surgical sterilization (hysterectomy, tubal ligation or vasectomy).

Exclusion Criteria

1. Participant is unable to tolerate the ocular instillations or follow study procedures.
2. Participant has a significant active infection (an infection requiring treatment as determined by the medical team) that in the principal investigator's best medical judgment would preclude participation.
3. Participant has multiple sclerosis (MS), as interferon gamma may cause MS exacerbations.

Primary outcomes:
measure: Change in Excess Central Macular Thickening in the Study Eye, as Measured by Optical Coherence Tomography (OCT), at Week One Compared to Baseline
timeFrame: Baseline and 1 Week
Secondary outcomes:
measure: Change in Excess Central Macular Thickening in the Fellow Eye, as Measured by Optical Coherence Tomography (OCT), at Week One Compared to Baseline
timeFrame: Baseline and 1 Week
measure: Change in Excess Central Macular Thickening in the Study Eye, as Measured by Optical Coherence Tomography (OCT), at Week Two Compared to Baseline
timeFrame: Baseline and 2 Weeks
measure: Change in Excess Central Macular Thickening in the Fellow Eye, as Measured by Optical Coherence Tomography (OCT), at Week Two Compared to Baseline
timeFrame: Baseline and 2 Weeks
measure: Change in Macular Volume in the Study Eye, as Measured by Optical Coherence Tomography (OCT), at Week One Compared to Baseline
timeFrame: Baseline and 1 Week
measure: Change in Macular Volume in the Fellow Eye, as Measured by Optical Coherence Tomography (OCT), at Week One Compared to Baseline
timeFrame: Baseline and 1 Week
measure: Change in Macular Volume in the Study Eye, as Measured by Optical Coherence Tomography (OCT), at Week Two Compared to Baseline
timeFrame: Baseline and 2 Weeks
measure: Change in Macular Volume in the Fellow Eye, as Measured by Optical Coherence Tomography (OCT), at Week Two Compared to Baseline
timeFrame: Baseline and 2 Weeks
measure: Change in ETDRS Best-corrected Visual Acuity (BCVA) in the Study Eye at Week One Compared to Baseline
timeFrame: Baseline and 1 Week
measure: Change in ETDRS Best-corrected Visual Acuity (BCVA) in the Fellow Eye at Week One Compared to Baseline
timeFrame: Baseline and 1 Week
measure: Change in ETDRS Best-corrected Visual Acuity (BCVA) in the Study Eye at Week Two Compared to Baseline
timeFrame: Baseline and 2 Weeks
measure: Change in ETDRS Best-corrected Visual Acuity (BCVA) in the Fellow Eye at Week Two Compared to Baseline
timeFrame: Baseline and 2 Weeks
measure: Change in Intraocular Pressure (IOP) in the Study Eye at Week One Compared to Baseline
timeFrame: Baseline and 1 Week
measure: Change in Intraocular Pressure (IOP) in the Fellow Eye at Week One Compared to Baseline
timeFrame: Baseline and 1 Week
measure: Change in Intraocular Pressure (IOP) in the Study Eye at Week Two Compared to Baseline
timeFrame: Baseline and 2 Weeks
measure: Change in Intraocular Pressure (IOP) in the Fellow Eye at Week Two Compared to Baseline
timeFrame: Baseline and 2 Weeks
measure: Proportion of Participants With a Visual Loss of 15 or More Early Treatment Diabetic Retinopathy Study (ETDRS) Letters in the Study Eye
timeFrame: Baseline and 2 Weeks
Other outcomes:
Locations:
city: Bethesda
country: United States
facility: National Institutes of Health Clinical Center, 9000 Rockville Pike
state: Maryland
Study officials:
affiliation: National Eye Institute (NEI)
name: Hatice Nida Sen, MD, MHSc
role: PRINCIPAL_INVESTIGATOR
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