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Topical Interferon Gamma for Macular Edema Secondary to Uveitis (JakStat2)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Nida Sen, National Institutes of Health Clinical Center (CC)
ClinicalTrials.gov Identifier:
NCT01376362
First received: June 17, 2011
Last updated: September 6, 2012
Last verified: September 2012
  Purpose

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.


Condition Intervention Phase
Anterior Uveitis
Uveitis
Drug: Interferon Gamma-1b
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: The Treatment of Macular Edema Secondary to Uveitis Using Topical Interferon Gamma

Resource links provided by NLM:


Further study details as provided by National Institutes of Health Clinical Center (CC):

Primary Outcome Measures:
  • Change in Excess Central Macular Thickening in the Study Eye, as Measured by Optical Coherence Tomography (OCT), at Week One Compared to Baseline [ Time Frame: Baseline and 1 Week ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Change in Excess Central Macular Thickening in the Fellow Eye, as Measured by Optical Coherence Tomography (OCT), at Week One Compared to Baseline [ Time Frame: Baseline and 1 Week ] [ Designated as safety issue: No ]
    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.

  • Change in Excess Central Macular Thickening in the Study Eye, as Measured by Optical Coherence Tomography (OCT), at Week Two Compared to Baseline [ Time Frame: Baseline and 2 Weeks ] [ Designated as safety issue: No ]
    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.

  • Change in Excess Central Macular Thickening in the Fellow Eye, as Measured by Optical Coherence Tomography (OCT), at Week Two Compared to Baseline [ Time Frame: Baseline and 2 Weeks ] [ Designated as safety issue: No ]
    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.

  • Change in Macular Volume in the Study Eye, as Measured by Optical Coherence Tomography (OCT), at Week One Compared to Baseline [ Time Frame: Baseline and 1 Week ] [ Designated as safety issue: No ]
    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.

  • Change in Macular Volume in the Fellow Eye, as Measured by Optical Coherence Tomography (OCT), at Week One Compared to Baseline [ Time Frame: Baseline and 1 Week ] [ Designated as safety issue: No ]
    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.

  • Change in Macular Volume in the Study Eye, as Measured by Optical Coherence Tomography (OCT), at Week Two Compared to Baseline [ Time Frame: Baseline and 2 Weeks ] [ Designated as safety issue: No ]
    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.

  • Change in Macular Volume in the Fellow Eye, as Measured by Optical Coherence Tomography (OCT), at Week Two Compared to Baseline [ Time Frame: Baseline and 2 Weeks ] [ Designated as safety issue: No ]
    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.

  • Change in ETDRS Best-corrected Visual Acuity (BCVA) in the Study Eye at Week One Compared to Baseline [ Time Frame: Baseline and 1 Week ] [ Designated as safety issue: No ]
    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.

  • Change in ETDRS Best-corrected Visual Acuity (BCVA) in the Fellow Eye at Week One Compared to Baseline [ Time Frame: Baseline and 1 Week ] [ Designated as safety issue: No ]
    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.

  • Change in ETDRS Best-corrected Visual Acuity (BCVA) in the Study Eye at Week Two Compared to Baseline [ Time Frame: Baseline and 2 Weeks ] [ Designated as safety issue: No ]
    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.

  • Change in ETDRS Best-corrected Visual Acuity (BCVA) in the Fellow Eye at Week Two Compared to Baseline [ Time Frame: Baseline and 2 Weeks ] [ Designated as safety issue: No ]
    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.

  • Change in Intraocular Pressure (IOP) in the Study Eye at Week One Compared to Baseline [ Time Frame: Baseline and 1 Week ] [ Designated as safety issue: No ]
    Intraocular pressure was recorded using a standard Goldmann applanation tonometer, a device for the measurement of intraocular pressure between 0 to 78 mm Hg.

  • Change in Intraocular Pressure (IOP) in the Fellow Eye at Week One Compared to Baseline [ Time Frame: Baseline and 1 Week ] [ Designated as safety issue: No ]
    Intraocular pressure was recorded using a standard Goldmann applanation tonometer, a device for the measurement of intraocular pressure between 0 to 78 mm Hg.

  • Change in Intraocular Pressure (IOP) in the Study Eye at Week Two Compared to Baseline [ Time Frame: Baseline and 2 Weeks ] [ Designated as safety issue: No ]
    Intraocular pressure was recorded using a standard Goldmann applanation tonometer, a device for the measurement of intraocular pressure between 0 to 78 mm Hg.

  • Change in Intraocular Pressure (IOP) in the Fellow Eye at Week Two Compared to Baseline [ Time Frame: Baseline and 2 Weeks ] [ Designated as safety issue: No ]
    Intraocular pressure was recorded using a standard Goldmann applanation tonometer, a device for the measurement of intraocular pressure between 0 to 78 mm Hg.

  • Proportion of Participants With a Visual Loss of 15 or More Early Treatment Diabetic Retinopathy Study (ETDRS) Letters in the Study Eye [ Time Frame: Baseline and 2 Weeks ] [ Designated as safety issue: Yes ]
    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.


Enrollment: 5
Study Start Date: June 2011
Study Completion Date: March 2012
Primary Completion Date: February 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 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.
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.
Other Name: Actimmune®

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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01376362

Locations
United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, United States, 20892
Sponsors and Collaborators
Investigators
Principal Investigator: Hatice Nida Sen, MD, MHSc National Eye Institute (NEI)
  More Information

Publications:
Responsible Party: Nida Sen, Principal Investigator, NEI, National Institutes of Health Clinical Center (CC)
ClinicalTrials.gov Identifier: NCT01376362     History of Changes
Other Study ID Numbers: 110167, 11-EI-0167
Study First Received: June 17, 2011
Results First Received: August 3, 2012
Last Updated: September 6, 2012
Health Authority: United States: Federal Government
United States: Food and Drug Administration

Keywords provided by National Institutes of Health Clinical Center (CC):
Cystoid Macular Edema
Intermediate Uveitis
Uveitis
OCT
Interferon-Gamma (IFN-Gamma)

Additional relevant MeSH terms:
Chorioretinitis
Iridocyclitis
Macular Edema
Uveitis
Uveitis, Anterior
Choroid Diseases
Choroiditis
Eye Diseases
Iris Diseases
Macular Degeneration
Panuveitis
Retinal Degeneration
Retinal Diseases
Retinitis
Uveal Diseases
Uveitis, Posterior
Interferon-gamma
Interferons
Anti-Infective Agents
Antineoplastic Agents
Antiviral Agents
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on November 25, 2014