Topical Interferon Gamma for Macular Edema Secondary to Uveitis

Uveitis Clinical Trial

— JakStat2  

Official title:

The Treatment of Macular Edema Secondary to Uveitis Using Topical Interferon Gamma

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01376362
• Other study ID #: 110167
• Secondary ID: 11-EI-0167
• Status: Completed
• Phase: Phase 1/Phase 2
• First received: June 17, 2011
• Last updated: September 6, 2012
• Start date: June 2011
• Est. completion date: March 2012

Study information

• Verified date: September 2012
• Source: National Institutes of Health Clinical Center (CC)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal GovernmentUnited States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 5
• Est. completion date: March 2012
• Est. primary completion date: February 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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.

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Anterior Uveitis
• Iridocyclitis
• Iritis
• Macular Edema
• Uveitis
• Uveitis, Anterior

Intervention

Drug:
• Interferon Gamma-1b
Interferon gamma-1b (Actimmune®, InterMune, Inc, Brisbane, CA 94005) was supplied to participants in single-use dropperettes. Each dropperette contained approximately 0.2 mL of interferon gamma-1b (Actimmune®). Participants received 28 dropperettes at the baseline visit and were instructed to place four drops (approximately 7 µg per drop) topically on the cornea of the study eye four times per day for seven days.

Locations

Country	Name	City	State
United States	National Institutes of Health Clinical Center, 9000 Rockville Pike	Bethesda	Maryland

Sponsors (1)

Lead Sponsor	Collaborator
National Eye Institute (NEI)

Country where clinical trial is conducted

United States, 

References & Publications (3)

Battle TE, Lynch RA, Frank DA. Signal transducer and activator of transcription 1 activation in endothelial cells is a negative regulator of angiogenesis. Cancer Res. 2006 Apr 1;66(7):3649-57. — View Citation

Khorana HG. Rhodopsin, photoreceptor of the rod cell. An emerging pattern for structure and function. J Biol Chem. 1992 Jan 5;267(1):1-4. Review. — View Citation

Shi G, Maminishkis A, Banzon T, Jalickee S, Li R, Hammer J, Miller SS. Control of chemokine gradients by the retinal pigment epithelium. Invest Ophthalmol Vis Sci. 2008 Oct;49(10):4620-30. doi: 10.1167/iovs.08-1816. Epub 2008 Apr 30. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in Excess Central Macular Thickening in the Study Eye, as Measured by Optical Coherence Tomography (OCT), at Week One Compared to Baseline	Central macular thickness was assessed by spectral-domain optical coherence tomography (Cirrus HD-OCT; Carl Zeiss Meditec, Dublin, CA), a non-invasive imaging technique that uses long-wavelength light to capture micrometer-resolution cross-sectional images from biological tissue.	Baseline and 1 Week	No
Secondary	Change in Excess Central Macular Thickening in the Fellow Eye, as Measured by Optical Coherence Tomography (OCT), at Week One Compared to Baseline	Central macular thickness was assessed by spectral-domain optical coherence tomography (Cirrus HD-OCT; Carl Zeiss Meditec, Dublin, CA), a non-invasive imaging technique that uses long-wavelength light to capture micrometer-resolution cross-sectional images from biological tissue.	Baseline and 1 Week	No
Secondary	Change in Excess Central Macular Thickening in the Study Eye, as Measured by Optical Coherence Tomography (OCT), at Week Two Compared to Baseline	Central macular thickness was assessed by spectral-domain optical coherence tomography (Cirrus HD-OCT; Carl Zeiss Meditec, Dublin, CA), a non-invasive imaging technique that uses long-wavelength light to capture micrometer-resolution cross-sectional images from biological tissue.	Baseline and 2 Weeks	No
Secondary	Change in Excess Central Macular Thickening in the Fellow Eye, as Measured by Optical Coherence Tomography (OCT), at Week Two Compared to Baseline	Central macular thickness was assessed by spectral-domain optical coherence tomography (Cirrus HD-OCT; Carl Zeiss Meditec, Dublin, CA), a non-invasive imaging technique that uses long-wavelength light to capture micrometer-resolution cross-sectional images from biological tissue.	Baseline and 2 Weeks	No
Secondary	Change in Macular Volume in the Study Eye, as Measured by Optical Coherence Tomography (OCT), at Week One Compared to Baseline	Macular volume was assessed by spectral-domain optical coherence tomography (Cirrus HD-OCT; Carl Zeiss Meditec, Dublin, CA), a non-invasive imaging technique that uses long-wavelength light to capture micrometer-resolution cross-sectional images from biological tissue.	Baseline and 1 Week	No
Secondary	Change in Macular Volume in the Fellow Eye, as Measured by Optical Coherence Tomography (OCT), at Week One Compared to Baseline	Macular volume was assessed by spectral-domain optical coherence tomography (Cirrus HD-OCT; Carl Zeiss Meditec, Dublin, CA), a non-invasive imaging technique that uses long-wavelength light to capture micrometer-resolution cross-sectional images from biological tissue.	Baseline and 1 Week	No
Secondary	Change in Macular Volume in the Study Eye, as Measured by Optical Coherence Tomography (OCT), at Week Two Compared to Baseline	Macular volume was assessed by spectral-domain optical coherence tomography (Cirrus HD-OCT; Carl Zeiss Meditec, Dublin, CA), a non-invasive imaging technique that uses long-wavelength light to capture micrometer-resolution cross-sectional images from biological tissue.	Baseline and 2 Weeks	No
Secondary	Change in Macular Volume in the Fellow Eye, as Measured by Optical Coherence Tomography (OCT), at Week Two Compared to Baseline	Macular volume was assessed by spectral-domain optical coherence tomography (Cirrus HD-OCT; Carl Zeiss Meditec, Dublin, CA), a non-invasive imaging technique that uses long-wavelength light to capture micrometer-resolution cross-sectional images from biological tissue.	Baseline and 2 Weeks	No
Secondary	Change in ETDRS Best-corrected Visual Acuity (BCVA) in the Study Eye at Week One Compared to Baseline	Visual acuity was measured using the Early Treatment Diabetic Retinopathy Study (ETDRS) protocol. Acuity is measured as letters read on an ETDRS eye chart and the letters read equate to Snellen measurements. For example, if a participant reads between 84 and 88 letters, the equivalent Snellen measurement is 20/20.	Baseline and 1 Week	No
Secondary	Change in ETDRS Best-corrected Visual Acuity (BCVA) in the Fellow Eye at Week One Compared to Baseline	Visual acuity was measured using the Early Treatment Diabetic Retinopathy Study (ETDRS) protocol. Acuity is measured as letters read on an ETDRS eye chart and the letters read equate to Snellen measurements. For example, if a participant reads between 84 and 88 letters, the equivalent Snellen measurement is 20/20.	Baseline and 1 Week	No
Secondary	Change in ETDRS Best-corrected Visual Acuity (BCVA) in the Study Eye at Week Two Compared to Baseline	Visual acuity was measured using the Early Treatment Diabetic Retinopathy Study (ETDRS) protocol. Acuity is measured as letters read on an ETDRS eye chart and the letters read equate to Snellen measurements. For example, if a participant reads between 84 and 88 letters, the equivalent Snellen measurement is 20/20.	Baseline and 2 Weeks	No
Secondary	Change in ETDRS Best-corrected Visual Acuity (BCVA) in the Fellow Eye at Week Two Compared to Baseline	Visual acuity was measured using the Early Treatment Diabetic Retinopathy Study (ETDRS) protocol. Acuity is measured as letters read on an ETDRS eye chart and the letters read equate to Snellen measurements. For example, if a participant reads between 84 and 88 letters, the equivalent Snellen measurement is 20/20.	Baseline and 2 Weeks	No
Secondary	Change in Intraocular Pressure (IOP) in the Study Eye at Week One Compared to Baseline	Intraocular pressure was recorded using a standard Goldmann applanation tonometer, a device for the measurement of intraocular pressure between 0 to 78 mm Hg.	Baseline and 1 Week	No
Secondary	Change in Intraocular Pressure (IOP) in the Fellow Eye at Week One Compared to Baseline	Intraocular pressure was recorded using a standard Goldmann applanation tonometer, a device for the measurement of intraocular pressure between 0 to 78 mm Hg.	Baseline and 1 Week	No
Secondary	Change in Intraocular Pressure (IOP) in the Study Eye at Week Two Compared to Baseline	Intraocular pressure was recorded using a standard Goldmann applanation tonometer, a device for the measurement of intraocular pressure between 0 to 78 mm Hg.	Baseline and 2 Weeks	No
Secondary	Change in Intraocular Pressure (IOP) in the Fellow Eye at Week Two Compared to Baseline	Intraocular pressure was recorded using a standard Goldmann applanation tonometer, a device for the measurement of intraocular pressure between 0 to 78 mm Hg.	Baseline and 2 Weeks	No
Secondary	Proportion of Participants With a Visual Loss of 15 or More Early Treatment Diabetic Retinopathy Study (ETDRS) Letters in the Study Eye	Visual acuity was measured using the Early Treatment Diabetic Retinopathy Study (ETDRS) protocol. Acuity is measured as letters read on an ETDRS eye chart and the letters read equate to Snellen measurements. For example, if a participant reads between 84 and 88 letters, the equivalent Snellen measurement is 20/20.	Baseline and 2 Weeks	Yes