Inherited Retinal Degeneration Clinical Trial
Official title:
Pilot Phase I/II Study of the Evaluation of Interferon Gamma-1b Administered Topically for Macular Edema/Intraretinal Schisis Cysts in Rod-Cone Dystrophy (RCD) and Enhanced S-Cone Syndrome (ESCS)
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.
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.
;
| Status | Clinical Trial | Phase | |
|---|---|---|---|
| Recruiting |
NCT05589714 -
Universal Rare Gene Study: A Registry and Natural History Study of Retinal Dystrophies Associated With Rare Disease-Causing Genetic Variants
|
||
| Completed |
NCT01878032 -
Color Vision as a Measure for Inherited Retinal Diseases
|
N/A |