Interferon Gamma-1b Administered Topically for Macular Edema/Intraretinal Schisis Cysts in Rod-Cone Dystrophy (RCD) and Enhanced S-Cone Syndrome (ESCS)

Phase 1

Terminated

Conditions: Inherited Retinal Degeneration
Inherited Ophthalmic Diseases

Interventions: Drug: Interferon gamma-1b

Registration Number: NCT02338973

Lead Sponsor: National Eye Institute (NEI)

Brief Summary: Background:

- People with rod-cone dystrophy (RCD) or enhanced S-cone syndrome (ESCS) have excess fluid under the retina of their eye. This can cause vision loss. The medicine interferon gamma-1b may help people with these diseases.

Objectives:

- To see if interferon gamma-1b eyedrops are safe for people with RCD or ESCS. To see if the medicine can decrease retina fluid and help prevent vision loss.

Eligibility:

- People at least 12 years old with RCD or ESCS. Those with ESCS must have two mutations in the NR2E3 gene.

Design:

* Participants will be screened with medical history, physical exam, eye exam, and blood tests.

* Participants will stay at NIH for 3 days and get the first eyedrops.

* Participants will give themselves 4 study eyedrops 4 times daily for 2 weeks and keep a diary.

* Participants will have 5 outpatient visits over 8 weeks, 2 of which are telephone assessments. They may have:

* Repeats of screening tests.

* Questionnaires.

* Small piece of skin removed.

* Eye exams, including eye dilation and tasks on computer screens.

* Fluorescein angiography. A dye injected into an arm vein will travel to the blood vessels in the eyes. A camera will take pictures.

* Electroretinography. Participants will sit in the dark wearing eyepatches. A small electrode will be taped to the forehead. After 30 minutes, researchers will remove the eyepatches and put in numbing eyedrops and contact lenses. Participants will watch flashing lights.

* Electrooculography. Electrodes will be attached outside of the eyes and eye function will be measured in the dark and the light.

* Participants will have a follow-up visit after 52 weeks.

Detailed Description: Objective:

Rod-cone dystrophy (RCD) is a term applied to a number of genetically heterogenous diseases presenting with night vision abnormalities, visual field defects and reduced rod electroretinography responses. Enhanced S-Cone syndrome (ESCS) is a rare autosomal recessive retinal disease with a developmental and a degenerative aspect. Macular cystic changes, often florid and usually resulting in a reduction of central acuity, are frequently associated with both diseases. The reason for this association is not well understood. Acetazolamide (Diamox) and Dorzolamide (Trusopt) have been reported to have variable success in reducing these cystic changes but the effect is frequently inadequate. The objective of this study is to evaluate the safety and potential efficacy of Interferon (IFN) gamma-1b administered topically for macular edema/retinal schisis cysts in RCD and ESCS. Possible disease-related pathophysiologic mechanisms will be explored using induced pluripotent stem cell (iPSC) protocols leading to iPSC-derived retinal pigment epithelium (RPE) and photoreceptor generation.

Study Population:

Up to five participants with RCD with significant macular cystic changes and up to five participants with ESCS with significant macular cystic changes will be enrolled to receive IFN gamma-1b administered topically in one eye. However, up to an additional two participants may be enrolled in order to obtain the five participants in each disease group to be included in the primary analysis if any participants withdraw from the study prior to receiving five days of treatment.

Design:

This is a single-center, prospective, uncontrolled, unmasked pilot Phase I/II study of the safety, tolerability and possible efficacy of IFN gamma-1b in participants with RCD and ESCS and macular cystic changes. One eye of up to five participants with RCD with significant macular cystic changes and up to five participants with ESCS with significant macular cystic changes \[evidenced by optical coherence tomography (OCT) \>275 microns central macular thickness and/or disruption of foveal contour\] will receive topical IFN gamma-1b instilled as drops on the cornea. The initial stage of the study will include two participants from each disease category. Once all four participants have completed the 8-week visit, enrollment will be halted. Safety Adverse Event Review Committee members unaffiliated with the study will review the data as a preliminary assessment of safety and efficacy and to determine whether enrollment should continue. If the committee determines enrollment will continue, three additional participants with RCD and three participants with ESCS will be enrolled. The study will be completed once the final participant has received one year of follow-up.

Outcome Measures:

The primary outcome measure related to the safety and tolerability of IFN gamma-1b administered topically at the prescribed dosage for macular cystic changes in participants with RCD and ESCS will be assessed by the number and severity of adverse events related to the IP and the number of withdrawals at 52 weeks (one year) post-administration. Additional safety of IFN gamma-1b administered topically in participants with RCD and ESCS will be determined from the assessment of retinal function, ocular structure and occurrence of adverse events at all time points. Secondary outcomes include changes in visual function including visual acuity and microperimetry, and retinal imaging with OCT and fluorescein angiography.

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 4

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Interferon Gamma-1b	Interferon gamma-1b	Topical interferon (IFN) gamma-1b, 112 µg dose, administered in study eye daily for two weeks

Primary Outcome Measures

Name	Time	Method
Number and Severity of IP-related AEs	Study duration, up to 52 weeks	The number and severity of adverse events related to the investigation product (IP).
Number of Participants Who Withdrew	Study duration, up to 52 weeks	The number of participants who withdrew early.

Secondary Outcome Measures

Name	Time	Method
Change in Best Corrected Visual Acuity (BCVA) From Baseline as Compared to Day 2	Day 2	Change in BCVA from baseline as compared to Day 2 by participant in both study and fellow eyes.
Change in Central Retinal Thickness as Measured on Cirrus OCT From Baseline as Compared to Day 3	Day 3	Change in central retinal thickness as measured on Cirrus OCT from baseline as compared to Day 3 by participant in both study and fellow eyes.
Change in Central Retinal Thickness as Measured on Cirrus OCT From Baseline as Compared to Week 2	Week 2	Change in central retinal thickness as measured on Cirrus OCT from baseline as compared to Week 2 by participant in both study and fellow eyes.
Change in Best Corrected Visual Acuity (BCVA) From Baseline as Compared to Day 1	Day 1	Change in BCVA from baseline as compared to Day 1 by participant in both study and fellow eyes.
Change in Best Corrected Visual Acuity (BCVA) From Baseline as Compared to Day 3	Day 3	Change in BCVA from baseline as compared to Day 3 by participant in both study and fellow eyes.
Change in Best Corrected Visual Acuity (BCVA) From Baseline as Compared to Week 2	Week 2	Change in BCVA from baseline as compared to Week 2 by participant in both study and fellow eyes.
Change in Best Corrected Visual Acuity (BCVA) From Baseline as Compared to Week 5	Week 5	Change in BCVA from baseline as compared to Week 5 by participant in both study and fellow eyes.
Change in Best Corrected Visual Acuity (BCVA) From Baseline as Compared to Week 8	Week 8	Change in BCVA from baseline as compared to Week 8 by participant in both study and fellow eyes.
Change in Best Corrected Visual Acuity (BCVA) From Baseline as Compared to Week 52	Week 52	Change in BCVA from baseline as compared to Week 52 by participant in both study and fellow eyes.
Change in Maximum Subretinal Fluid Volume From Baseline as Compared to Day 1	Day 1	Change in maximum subretinal fluid volume as measured on OCT from baseline as compared to Day 1 by participant in both study and fellow eyes.
Change in Maximum Subretinal Fluid Volume From Baseline as Compared to Day 3	Day 3	Change in maximum subretinal fluid volume as measured on OCT from baseline as compared to Day 3 by participant in both study and fellow eyes.
Change in Maximum Subretinal Fluid Volume From Baseline as Compared to Week 2	Week 2	Change in maximum subretinal fluid volume as measured on OCT from baseline as compared to Week 2 by participant in both study and fellow eyes.
Change in Maximum Subretinal Fluid Volume From Baseline as Compared to Week 8	Week 8	Change in maximum subretinal fluid volume as measured on OCT from baseline as compared to Week 8 by participant in both study and fellow eyes.
Change in Maximum Subretinal Fluid Volume From Baseline as Compared to Day 2	Day 2	Change in maximum subretinal fluid volume as measured on OCT from baseline as compared to Day 2 by participant in both study and fellow eyes.
Change in Maximum Subretinal Fluid Volume From Baseline as Compared to Week 52	Week 52	Change in maximum subretinal fluid volume as measured on OCT from baseline as compared to Week 52 by participant in both study and fellow eyes.
Change in Central Retinal Thickness as Measured on Cirrus OCT From Baseline as Compared to Day 1	Day 1	Change in central retinal thickness as measured on Cirrus OCT from baseline as compared to Day 1 by participant in both study and fellow eyes.
Change in Central Retinal Thickness as Measured on Cirrus OCT From Baseline as Compared to Week 5	Week 5	Change in central retinal thickness as measured on Cirrus OCT from baseline as compared to Week 5 by participant in both study and fellow eyes.
Change in Central Retinal Thickness as Measured on Cirrus OCT From Baseline as Compared to Week 8	Week 8	Change in central retinal thickness as measured on Cirrus OCT from baseline as compared to Week 8 by participant in both study and fellow eyes.
Change in Central Retinal Thickness as Measured on Cirrus OCT From Baseline as Compared to Week 52	Week 52	Change in central retinal thickness as measured on Cirrus OCT from baseline as compared to Week 52 by participant in both study and fellow eyes.
Change in Maximum Subretinal Fluid Volume From Baseline as Compared to Week 5	Week 5	Change in maximum subretinal fluid volume as measured on OCT from baseline as compared to Week 5 by participant in both study and fellow eyes.
Change in Central Retinal Thickness as Measured on Cirrus OCT From Baseline as Compared to Day 2	Day 2	Change in central retinal thickness as measured on Cirrus OCT from baseline as compared to Day 2 by participant in both study and fellow eyes.
Change in Central Retinal Thickness as Measured on Spectralis OCT From Baseline as Compared to Day 1	Day 1	Change in central retinal thickness as measured on Spectralis OCT from baseline as compared to Day 1 by participant in both study and fellow eyes.
Change in Central Retinal Thickness as Measured on Spectralis OCT From Baseline as Compared to Day 2	Day 2	Change in central retinal thickness as measured on Spectralis OCT from baseline as compared to Day 2 by participant in both study and fellow eyes.
Change in Central Retinal Thickness as Measured on Spectralis OCT From Baseline as Compared to Week 2	Week 2	Change in central retinal thickness as measured on Spectralis OCT from baseline as compared to Week 2 by participant in both study and fellow eyes.
Change in Central Retinal Thickness as Measured on Spectralis OCT From Baseline as Compared to Week 5	Week 5	Change in central retinal thickness as measured on Spectralis OCT from baseline as compared to Week 5 by participant in both study and fellow eyes.
Change in Central Retinal Thickness as Measured on Spectralis OCT From Baseline as Compared to Week 8	Week 8	Change in central retinal thickness as measured on Spectralis OCT from baseline as compared to Week 8 by participant in both study and fellow eyes.
Change in Central Retinal Thickness as Measured on Spectralis OCT From Baseline as Compared to Week 52	Week 52	Change in central retinal thickness as measured on Spectralis OCT from baseline as compared to Week 52 by participant in both study and fellow eyes.
Change in Central Visual Field Sensitivity at Day 2 and Week 5 Compared to Baseline.	Day 2 and Week 5	Change in central visual field sensitivity as measured by microperimetry testing at Day 2 and Week 5 compared to baseline in both study and fellow eyes.
Change in Central Retinal Thickness as Measured on Spectralis OCT From Baseline as Compared to Day 3	Day 3	Change in central retinal thickness as measured on Spectralis OCT from baseline as compared to Day 3 by participant in both study and fellow eyes.