Dose Escalation Study to Evaluate the Safety/Tolerability and Efficacy of EA-2353 in Subjects With Retinitis Pigmentosa

Study Overview
=================
Brief Summary
-----------------
This is an open-label, multiple ascending dose study to evaluate the safety, tolerability, and efficacy of EA-2353 in subjects with RP. Unilateral intravitreal injections (IVT) will be administered into the subject's Study Eye. There will be up to 4 cohorts.

Detailed Description
-----------------
This is an open-label, multiple ascending dose study to evaluate the safety, tolerability, and efficacy of EA-2353 in subjects with RP. There will be up to 4 cohorts. Each of the first three cohorts will treat 3 subjects with 4 weekly injections of EA-2353. Unilateral intravitreal injections (IVT) will be administered into the subject's Study Eye, which is determined as the eye with worse vision based on the BCVA. Eligible subjects will be enrolled into one of the following three cohorts in an ascending sequential fashion: Cohort 1 (low dose) Cohort 2 (mid dose) Cohort 3 (high dose) Cohort 4 (maximum tolerated dose) Patient participation will last for approximately 25 months.

Official Title
-----------------
Open-label, Multiple Dose, Dose Escalation Study to Evaluate the Safety/Tolerability and Efficacy of EA-2353 in Subjects With Retinitis Pigmentosa

Conditions
-----------------
Retinitis Pigmentosa, Retinitis Pigmentosa Syndrome

Intervention / Treatment
-----------------
* Drug: EA-2353


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Male or female, ≥ 18 years of age. Have a clinical and molecular diagnosis of RP. Understand the language of the informed consent and are willing and able to provide written informed consent prior to any study procedures. Are willing to comply with the protocol and follow the instructions including attendance at all scheduled study visits. BCVA in the worse eye between 20/50 and able to count fingers (CF) Have clear ocular media. Have pupillary dilation sufficient to allow for quality images. Exclusion Criteria: Subjects who are pregnant or suspected to be pregnant and subjects who are lactating or intend to breastfeed. Female subjects of childbearing potential are required to have a negative urine pregnancy test at screening and prior to each injection, and must agree to use an acceptable method of contraception from the time of signing informed consent until the end of the study. Have any uncontrolled systemic disease or non-ocular disorder which would put the subject at risk due to study treatment or procedures, influence the results of the study, or impact the subject's ability to participate in the study (e.g., infection, uncontrolled elevated blood pressure, cardiovascular disease, and inability to maintain glycemic control). Presence of a significant ocular disease or disorder in the Study Eye. Have a history of any vitreoretinal surgery ever in the Study Eye. Have received any prior cell or gene therapy for RP. Have history or current abuse of alcohol and/or drugs.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: EA-2353 will be administered to all subjects during this study. It will be administered as 4 weekly intravitreal injections in the Study Eye.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: EA-2353<br>EA-2353 Ophthalmic Suspension will be administered via unilateral intravitreal injection into the Study Eye weekly for one month (4 injections) | Drug: EA-2353<br>* EA-2353 Ophthalmic Suspension<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence and severity of adverse events |  | through study completion at 24 months | 
| Incidence and severity of dose limiting toxicities (DLTs) |  | through study completion at 24 months | 
| Establish the maximum tolerated dose (MTD) as determined by occurrence of DLTs |  | through study completion at 24 months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
RP, Retinitis Pigmentosa, EA-2353, inherited retinal disease, IRD