Not provided
| ID | Type | Description | Link |
|---|---|---|---|
| 12-EI-0013 |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Class |
|---|---|
| The Emmes Company, LLC | INDUSTRY |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Background:
- In the eye disease central serous chorioretinopathy (CSC), fluid collects under the retina at the back of the eye. CSC can resolve on its own, but in some people it lasts for several months or can come back. The fluid buildup during CSC can cause vision loss. The drug interferon gamma-1b can help reduce fluid accumulation in the retina. Researchers want to see if interferon gamma-1b can help treat and prevent vision loss from CSC.
Objectives:
- To see if interferon gamma-1b eye drops are a safe and effective treatment for CSC.
Eligibility:
- Individuals at least 18 years of age who have CSC in at least one eye.
Design:
Objective: Central serous chorioretinopathy (CSC) is a retinal disorder characterized by an accumulation of serous fluid under the retina thought to be due to excessive choroidal hyperpermeability. The retinal pigment epithelium (RPE) plays a critical role in removing fluid from the subretinal space. This RPE "pump" is believed to be a key player in the reabsorption of subretinal fluid and maintenance of retinal attachment. Fluid transport assays have examined whether interferon gamma induces changes in fluid transport across human fetal RPE monolayers and showed an increase in fluid absorption from the retinal to the choroidal side of the tissue. An in vivo rodent model of retinal detachment has been used to measure the effect of interferon gamma on re-absorption following retinal detachment and showed that the addition of interferon gamma to the anterior eye surface caused a significant, rapid decrease in retinal detachment volume in the first hour of observation. This pilot study will investigate the safety, tolerability and potential efficacy of serial ocular instillations of topical interferon gamma-1b for classic CSC.
Study Population: Five participants with subretinal fluid due to classic CSC will initially be enrolled. However, up to an additional two participants may be enrolled in order to obtain the five participants to be included in the analysis if any participants withdraw from the study.
Design: In this Phase I/II, non-randomized, prospective, uncontrolled, dose-escalation, single-center pilot study, a series of ocular instillations of topical interferon gamma-1b will be administered in the study eye over a two-week period. If the fluid re-accumulates or increases, participants will be eligible for re-challenging with topical interferon gamma-1b in the study eye at Week 4. Participants will be followed for one year. Participants may be eligible for additional re-challenges after the initial eight week study period ends if their fluid re-accumulates or increases further.
Outcome Measures: The primary outcome measure related to the safety and tolerability of serial ocular instillations of topical interferon gamma-1b will be assessed by the number and severity of adverse events (AEs) related to the investigational product and the number of withdrawals. Secondary efficacy outcomes include changes in best-corrected visual acuity (BCVA), central retinal thickness and maximum lesion volume as measured on optical coherence tomography (OCT), leakage as observed on fluorescein angiograms (FA), autofluorescence patterns as observed on fundus autofluorescence (FAF) imaging and mean macular sensitivity as assessed by microperimetry.
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Interferon gamma-1b | Experimental | Interferon gamma-1b (Actimmune®, InterMune, Inc, Brisbane, CA 94005) was supplied to participants in single-use dropperettes. A single dropperette contains 1 mL of topical interferon gamma-1b (Actimmune®) at a concentration of 200 µg/mL, which is equivalent to 28 drops. Each drop provides a dose of 7 µg of investigational product. All participants will receive interferon gamma-1b for two weeks. Doses of interferon gamma-1b eye drops will be escalated among participants during this initial 2-week period; however, additional doses will be dispensed to participants if needed at Week 4 or after the initial 8-week study period. Participants eligible for additional doses after 8 weeks will be administered the maximum dose of 4 drops 4 times daily for a total daily dose of 112 μg. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Interferon gamma-1b | Drug | Participant 1: 2 drops of topical interferon gamma-1b three times daily in the study eye for a daily dose of 42 μg Participant 2: 3 drops 3 times daily in the study eye for a daily dose of 63 μg, if the 1st participant's dose is deemed well-tolerated by the investigator at Weeks 1, 2 and 4. Participant 3: 3 drops 4 times daily in the study eye for a daily dose of 84 μg, if the 2nd tolerates the daily dose of 63 μg at Weeks 1, 2 and 4. Participants 4 and 5: 4 drops 4 times daily in the study eye for a daily dose of 112 μg, if the 3rd tolerates the daily dose of 84 μg at Weeks 1, 2 and 4. If the 63, 84 or 112 μg doses are not well-tolerated, subsequent participants will be enrolled at the prior dose level (42, 63 or 84 μg). Well-tolerated is defined as no corneal irritation (e.g., punctuate epithelial keratitis), no coexisting conjunctival erythema and edema, and no signs of more serious toxicities (e.g., intraocular inflammation or lens changes). |
| Measure | Description | Time Frame |
|---|---|---|
| Total Number of Severe Ocular Adverse Events Related to the Investigational Product | Week 48 | |
| Total Number of Ocular Adverse Events Related to Investigational Product | Week 48 | |
| Total Number of Severe Non-ocular Adverse Events Related to the Investigational Product | Week 48 | |
| Total Number of Non-ocular Adverse Events Related to the Investigational Product | Week 48 | |
| Number of Participants Who Withdrew From the Study | Week 48 |
| Measure | Description | Time Frame |
|---|---|---|
| Changes in Best-corrected Visual Acuity (BCVA) in the Study Eye at Week 2 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. A positive change value indicates improvement of the outcome. A negative change value indicates worsening of the outcome. |
Not provided
INCLUSION CRITERIA:
Participant must be 18 years of age or older.
Participant must understand and sign the protocol s informed consent document.
Female participant of childbearing potential (see Appendix 1 for definition) must not be pregnant or breast-feeding, must have a negative pregnancy test at screening and must be willing to undergo pregnancy tests at scheduled study visits.
Female participant must be post-menopausal (see Appendix 1), must have had a hysterectomy, have a partner with a vasectomy, be completely abstinent from intercourse or must agree to practice two reliable methods of contraception throughout the course of the study and for six weeks after administration of investigational product. Acceptable methods of contraception include:
EXCLUSION CRITERIA:
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Emily Y Chew, M.D. | National Eye Institute (NEI) | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| National Institutes of Health Clinical Center, 9000 Rockville Pike | Bethesda | Maryland | 20892 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 19898183 | Background | Imamura Y, Fujiwara T, Margolis R, Spaide RF. Enhanced depth imaging optical coherence tomography of the choroid in central serous chorioretinopathy. Retina. 2009 Nov-Dec;29(10):1469-73. doi: 10.1097/IAE.0b013e3181be0a83. | |
| 10606450 | Background | Iida T, Kishi S, Hagimura N, Shimizu K. Persistent and bilateral choroidal vascular abnormalities in central serous chorioretinopathy. Retina. 1999;19(6):508-12. doi: 10.1097/00006982-199911000-00005. |
Not provided
Not provided
Not provided
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | Interferon Gamma-1b | Interferon gamma-1b (Actimmune®, InterMune, Inc, Brisbane, CA 94005) was supplied to participants in single-use dropperettes. A single dropperette contains 1 mL of topical interferon gamma-1b (Actimmune®) at a concentration of 200 µg/mL, which is equivalent to 28 drops. Each drop provides a dose of 7 µg of investigational product. All participants will receive interferon gamma-1b for two weeks. Doses of interferon gamma-1b eye drops will be escalated among participants during this initial 2-week period; however, additional doses will be dispensed to participants if needed at Week 4 or after the initial 8-week study period. Participants eligible for additional doses after 8 weeks will be administered the maximum dose of 4 drops 4 times daily for a total daily dose of 112 μg. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | Interferon Gamma-1b | Interferon gamma-1b (Actimmune®, InterMune, Inc, Brisbane, CA 94005) was supplied to participants in single-use dropperettes. A single dropperette contains 1 mL of topical interferon gamma-1b (Actimmune®) at a concentration of 200 µg/mL, which is equivalent to 28 drops. Each drop provides a dose of 7 µg of investigational product. All participants will receive interferon gamma-1b for two weeks. Doses of interferon gamma-1b eye drops will be escalated among participants during this initial 2-week period; however, additional doses will be dispensed to participants if needed at Week 4 or after the initial 8-week study period. Participants eligible for additional doses after 8 weeks will be administered the maximum dose of 4 drops 4 times daily for a total daily dose of 112 μg. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Total Number of Severe Ocular Adverse Events Related to the Investigational Product | Posted | Number | Adverse Events | Week 48 |
|
48 weeks
Not provided
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Interferon Gamma-1b | Interferon gamma-1b (Actimmune®, InterMune, Inc, Brisbane, CA 94005) was supplied to participants in single-use dropperettes. A single dropperette contains 1 mL of topical interferon gamma-1b (Actimmune®) at a concentration of 200 µg/mL, which is equivalent to 28 drops. Each drop provides a dose of 7 µg of investigational product. All participants will receive interferon gamma-1b for two weeks. Doses of interferon gamma-1b eye drops will be escalated among participants during this initial 2-week period; however, additional doses will be dispensed to participants if needed at Week 4 or after the initial 8-week study period. Participants eligible for additional doses after 8 weeks will be administered the maximum dose of 4 drops 4 times daily for a total daily dose of 112 μg. |
Not provided
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Asthenopia | Eye disorders | MedDRA 15.0 | Systematic Assessment |
After study completion, a participant presented with a cataract on 4/12/13 (last study dose:10/3/12 and TOTAL study dosage received: 2758 µg). Although age (58) was consistent with the possibility of cataract, relatedness to drug cannot be ruled out.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Emily Chew, MD | National Eye Institute | 301-496-6583 | emily.chew@nih.gov |
Not provided
| ID | Term |
|---|---|
| D012164 | Retinal Diseases |
| D008268 | Macular Degeneration |
| D056833 | Central Serous Chorioretinopathy |
| ID | Term |
|---|---|
| D005128 | Eye Diseases |
| D012162 | Retinal Degeneration |
Not provided
Not provided
| ID | Term |
|---|---|
| C554125 | interferon gamma-1b |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
|
|
| Baseline and Week 2 |
| Changes in Best-corrected Visual Acuity (BCVA) in the Fellow Eye at Week 2 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. A positive change value indicates improvement of the outcome. A negative change value indicates worsening of the outcome. | Baseline and Week 2 |
| Changes in Best-corrected Visual Acuity (BCVA) in the Study Eye at Week 48 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. A positive change value indicates improvement of the outcome. A negative change value indicates worsening of the outcome. | Baseline and Week 48 |
| Changes in Best-corrected Visual Acuity (BCVA) in the Fellow Eye at Week 48 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. A positive change value indicates improvement of the outcome. A negative change value indicates worsening of the outcome. | Baseline and Week 48 |
| Changes in the Maximum Subretinal Fluid Volume as Measured on Optical Coherence Tomography (OCT) at Week 2 Compared to Baseline | Baseline and Week 2 |
| Changes in Central Retinal Thickness as Measured on Optical Coherence Tomography (OCT) at Week 2 Compared to Baseline | Baseline and Week 2 |
| Changes in Leakage as Observed on Fluorescein Angiography (FA) at Week 2 Compared to Baseline | Baseline and Week 2 |
| Changes in the Autofluorescence Patterns as Observed on Fundus Autofluorescence (FAF) Imaging at Week 2 Compared to Baseline | Baseline and Week 2 |
| Changes in Mean Macular Sensitivity as Assessed by Microperimetry at Week 2 Compared to Baseline | Baseline and Week 2 |
| Changes in the Maximum Subretinal Fluid Volume as Measured on Optical Coherence Tomography (OCT) at Week 48 Compared to Baseline | Baseline and Week 48 |
| Changes in Central Retinal Thickness as Measured on Optical Coherence Tomography (OCT) at Week 48 Compared to Baseline | Baseline and Week 48 |
| Changes in Leakage as Observed on Fluorescein Angiography (FA) at Week 48 Compared to Baseline | Baseline and Week 48 |
| Changes in the Autofluorescence Patterns as Observed on Fundus Autofluorescence (FAF) Imaging at Week 48 Compared to Baseline | Baseline and Week 48 |
| Changes in Mean Macular Sensitivity as Assessed by Microperimetry at Week 48 Compared to Baseline | Baseline and Week 48 |
| 8554078 | Background | Prunte C, Flammer J. Choroidal capillary and venous congestion in central serous chorioretinopathy. Am J Ophthalmol. 1996 Jan;121(1):26-34. doi: 10.1016/s0002-9394(14)70531-8. |
| Participants |
|
| Sex: Female, Male | Count of Participants | Participants |
|
|
|
| Primary | Total Number of Ocular Adverse Events Related to Investigational Product | Posted | Number | Adverse Events | Week 48 |
|
|
|
| Primary | Total Number of Severe Non-ocular Adverse Events Related to the Investigational Product | Posted | Number | Adverse Events | Week 48 |
|
|
|
| Primary | Total Number of Non-ocular Adverse Events Related to the Investigational Product | Posted | Number | Adverse Events | Week 48 |
|
|
|
| Primary | Number of Participants Who Withdrew From the Study | Posted | Number | participants | Week 48 |
|
|
|
| Secondary | Changes in Best-corrected Visual Acuity (BCVA) in the Study Eye at Week 2 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. A positive change value indicates improvement of the outcome. A negative change value indicates worsening of the outcome. | Posted | Mean | Full Range | ETDRS letters | Baseline and Week 2 | Eyes | Eyes |
|
|
|
| Secondary | Changes in Best-corrected Visual Acuity (BCVA) in the Fellow Eye at Week 2 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. A positive change value indicates improvement of the outcome. A negative change value indicates worsening of the outcome. | Posted | Mean | Full Range | ETDRS letters | Baseline and Week 2 | Eyes | Eyes |
|
|
|
| Secondary | Changes in Best-corrected Visual Acuity (BCVA) in the Study Eye at Week 48 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. A positive change value indicates improvement of the outcome. A negative change value indicates worsening of the outcome. | Posted | Mean | Full Range | ETDRS letters | Baseline and Week 48 | Eyes | Eyes |
|
|
|
| Secondary | Changes in Best-corrected Visual Acuity (BCVA) in the Fellow Eye at Week 48 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. A positive change value indicates improvement of the outcome. A negative change value indicates worsening of the outcome. | Posted | Mean | Full Range | ETDRS letters | Baseline and Week 48 | Eyes | Eyes |
|
|
|
| Secondary | Changes in the Maximum Subretinal Fluid Volume as Measured on Optical Coherence Tomography (OCT) at Week 2 Compared to Baseline | Due to lack of effect in other outcome measures, at investigator's discretion, data for this outcome measure was neither collected nor analyzed. As such, zero participants have data for this outcome. | Posted | Baseline and Week 2 |
|
|
| Secondary | Changes in Central Retinal Thickness as Measured on Optical Coherence Tomography (OCT) at Week 2 Compared to Baseline | Due to lack of effect in other outcome measures, at investigator's discretion, data for this outcome measure was neither collected nor analyzed. As such, zero participants have data for this outcome. | Posted | Baseline and Week 2 |
|
|
| Secondary | Changes in Leakage as Observed on Fluorescein Angiography (FA) at Week 2 Compared to Baseline | Due to lack of effect in other outcome measures, at investigator's discretion, data for this outcome measure was neither collected nor analyzed. As such, zero participants have data for this outcome. | Posted | Baseline and Week 2 |
|
|
| Secondary | Changes in the Autofluorescence Patterns as Observed on Fundus Autofluorescence (FAF) Imaging at Week 2 Compared to Baseline | Due to lack of effect in other outcome measures, at investigator's discretion, data for this outcome measure was neither collected nor analyzed. As such, zero participants have data for this outcome. | Posted | Baseline and Week 2 |
|
|
| Secondary | Changes in Mean Macular Sensitivity as Assessed by Microperimetry at Week 2 Compared to Baseline | Due to lack of effect in other outcome measures, at investigator's discretion, data for this outcome measure was neither collected nor analyzed. As such, zero participants have data for this outcome. | Posted | Baseline and Week 2 |
|
|
| Secondary | Changes in the Maximum Subretinal Fluid Volume as Measured on Optical Coherence Tomography (OCT) at Week 48 Compared to Baseline | Due to lack of effect in other outcome measures, at investigator's discretion, data for this outcome measure was neither collected nor analyzed. As such, zero participants have data for this outcome. | Posted | Baseline and Week 48 |
|
|
| Secondary | Changes in Central Retinal Thickness as Measured on Optical Coherence Tomography (OCT) at Week 48 Compared to Baseline | Due to lack of effect in other outcome measures, at investigator's discretion, data for this outcome measure was neither collected nor analyzed. As such, zero participants have data for this outcome. | Posted | Baseline and Week 48 |
|
|
| Secondary | Changes in Leakage as Observed on Fluorescein Angiography (FA) at Week 48 Compared to Baseline | Due to lack of effect in other outcome measures, at investigator's discretion, data for this outcome measure was neither collected nor analyzed. As such, zero participants have data for this outcome. | Posted | Baseline and Week 48 |
|
|
| Secondary | Changes in the Autofluorescence Patterns as Observed on Fundus Autofluorescence (FAF) Imaging at Week 48 Compared to Baseline | Due to lack of effect in other outcome measures, at investigator's discretion, data for this outcome measure was neither collected nor analyzed. As such, zero participants have data for this outcome. | Posted | Baseline and Week 48 |
|
|
| Secondary | Changes in Mean Macular Sensitivity as Assessed by Microperimetry at Week 48 Compared to Baseline | Due to lack of effect in other outcome measures, at investigator's discretion, data for this outcome measure was neither collected nor analyzed. As such, zero participants have data for this outcome. | Posted | Baseline and Week 48 |
|
|
| 0 |
| 5 |
| 5 |
| 5 |
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA 15.1 | Systematic Assessment |
|
| Burning sensation | Nervous system disorders | MedDRA 15.0 | Systematic Assessment |
|
| Conjunctival hyperaemia | Eye disorders | MedDRA 15.0-15.1 | Systematic Assessment |
|
| Eye pruritis | Eye disorders | MedDRA 15.0-15.1 | Systematic Assessment |
|
| Nasal discomfort | Respiratory, thoracic and mediastinal disorders | MedDRA 15.1 | Systematic Assessment |
|
| Ocular hyperaemia | Eye disorders | MedDRA 15.0 | Systematic Assessment |
|
| Ocular hypertension | Eye disorders | MedDRA 15.1 | Systematic Assessment |
|
| Periorbital oedema | Eye disorders | MedDRA 16.0 | Systematic Assessment |
|
| Prostate infection | Infections and infestations | MedDRA 15.1 | Systematic Assessment |
|
| Pruritis generalised | Skin and subcutaneous tissue disorders | MedDRA 16.0 | Systematic Assessment |
|
| Urinary tract infection | Infections and infestations | MedDRA 15.0 | Systematic Assessment |
|
Not provided
Not provided
Not provided