A Study to Evaluate the Safety and Tolerability of ONL1204 in Patients With Macula-off, Rhegmatogenous Retinal Detachment

A Phase 1 Open-Label, Dose Escalation Study to Assess the Safety and Tolerability of Intravitreal ONL1204 in Patients With Macula-off, Rhegmatogenous Retinal Detachment

The purpose of this study is to evaluate the safety and tolerability of ONL1204 in participants with Macula-off, Rhegmatogenous Retinal Detachment (RRD). RRD is an acute and serious vision threatening condition in which a tear in the retina, typically resulting from a vitreous detachment, allows liquid to accumulate under the retina, detaching the photoreceptor (PR) layer of the retina from the retinal pigment epithelium (RPE). As the RPE is the principal source of nutritional support for the PR layer, the photoreceptors begin a cascade of inflammation and cell death. Photoreceptor cell death is the primary mechanism of vision loss after retinal detachment.

ONL1204 is a first-in-class inhibitor of Fragment Apoptosis Stimulator receptor (Fas)-mediated cell death. ONL1204 has demonstrated protection of multiple retinal cell types in numerous preclinical models of acute ocular injury. This will be a first-in-human (FIH) study to evaluate safety and tolerability of a single-dose of ONL1204 in participants with macula-off RRD. The standard of care for surgical repair of macula-off RRD is reattachment surgery within 7 days of the macula detaching. Participants in this study will receive a single intravitreal injection upon diagnosis and enrollment in the study, followed by standard of care surgery. The surgery includes vitrectomy, a procedure that removes the bulk of drug remaining in the vitreous.

Study Overview

• Status: Completed
• Conditions: Rhegmatogenous Retinal Detachment - Macula Off
• Intervention / Treatment: Drug: ONL1204; Procedure: Intravitreal Injection; Procedure: Collection of ocular fluids

• Study Type: Interventional
• Enrollment (Actual): 14
• Phase: Phase 1

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Sydney, New South Wales, Australia, 2000
      • Save Sight Institute, Sydney Eye Hospital
  • Victoria
    • Melbourne, Victoria, Australia, 3002
      • Royal Adelaide
    • Melbourne, Victoria, Australia, 4101
      • Queensland Eye Institute
    • Melbourne, Victoria, Australia, VIC 3002
      • Center for Eye Rearch Australia

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 78 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Males and females, ≥ 18 to 80 years old
2. Able to give informed consent and comply with all study visits and procedures

3. Patients who:

   1. Present between 1 week (7 days) and 4 weeks (28 days) of a macula-off RRD (based on patient-reported history of loss of central vision)
   2. For whom standard retinal reattachment surgery by means of a pars plana vitrectomy (with or without scleral buckle) and gas tamponade is indicated, and
   3. In the opinion of the investigator, can safely undergo all study procedures.
4. Best corrected Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity of 20/100 to hand motion in the study eye
5. Best corrected ETDRS visual acuity in the fellow eye of 20/60 or better

Exclusion Criteria:

1. Presence of giant retinal tear defined as greater than 3 clock hours or other type of complex retinal detachment in the study eye
2. Presence of vitreous hemorrhage in the study eye
3. Presence of ocular or periocular infection or intraocular inflammation in either eye
4. Intraocular Pressure > 22 mmHg in the study eye
5. Any other significant ocular disease in the study eye including media opacity that, in the opinion of the investigator, would preclude a visual acuity of at least 20/25 following successful vitrectomy or limit adequate visibility of the retina
6. Any other ocular pathology in the study eye requiring treatment with topical ophthalmic drops or intravitreal injection
7. History of previous ocular surgery in the study eye other than uncomplicated cataract surgery with posterior chamber intraocular lens and intact posterior capsule (which must have occurred at least 6 months prior to the baseline visit)
8. Participation in other clinical trials or use of any other investigational drugs or devices within 3 months prior to study participation
9. Females who are pregnant or lactating and women of childbearing potential who are not using adequate contraceptive precautions (e.g., intrauterine device, oral contraceptives, barrier method, or other contraception deemed adequate by the investigator)
10. Known retinopathy, known hepatic disease (or history of significant chronic liver disease), or known renal disease. Patients with diabetes and no known retinopathy may be enrolled
11. History of uncontrolled hypertension
12. History of stroke, transient ischemic attack, or major cardiac surgery within 3 months prior to study, or current treatment for systemic infection
13. Any ocular or systemic condition that in the opinion of the investigator could compromise the safety of the patient, or may interfere with the safety and tolerability assessments or study procedures of the trial

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Cohort 1 Dose A; Intravitreal injection of 50 μl of ONL1204 liquid formulation to deliver dose 1	Drug: ONL1204; Administration of ONL1204 - inhibitor of Fas(CD95) signaling by intravitreal injection; Procedure: Intravitreal Injection; Injection of study drug into the eye; Procedure: Collection of ocular fluids; vitreous and aqueous fluid collection by a tap and during vitrectomy
Active Comparator: Cohort 2 Dose B; Intravitreal injection of 100 μl of ONL1204 liquid formulation to deliver dose 2	Drug: ONL1204; Administration of ONL1204 - inhibitor of Fas(CD95) signaling by intravitreal injection; Procedure: Intravitreal Injection; Injection of study drug into the eye; Procedure: Collection of ocular fluids; vitreous and aqueous fluid collection by a tap and during vitrectomy
Active Comparator: Cohort 3 Dose C; Intravitreal injection of 50 μl of ONL1204 liquid formulation to deliver dose 3	Drug: ONL1204; Administration of ONL1204 - inhibitor of Fas(CD95) signaling by intravitreal injection; Procedure: Intravitreal Injection; Injection of study drug into the eye; Procedure: Collection of ocular fluids; vitreous and aqueous fluid collection by a tap and during vitrectomy
Active Comparator: Cohort 4 Dose D; Intravitreal injection of 100 μl of ONL1204 liquid formulation to deliver dose 4	Drug: ONL1204; Administration of ONL1204 - inhibitor of Fas(CD95) signaling by intravitreal injection; Procedure: Intravitreal Injection; Injection of study drug into the eye; Procedure: Collection of ocular fluids; vitreous and aqueous fluid collection by a tap and during vitrectomy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Vital sign-systolic and diastolic blood pressure	Systolic and diastolic blood pressure in mmHg	24 weeks
Vital sign-heart rate	Heart rate in beats per minute	24 weeks
Best corrected visual acuity	ETDRS chart (number of letters read)	24 weeks
Intraocular pressure	Intraocular pressure in mmHg	24 weeks
Slit lamp biomicroscopy	Slit lamp biomicroscopy (using US FDA clinical grading scale 0-4; 0=normal, 4=very severe changes)	24 weeks
Complete blood count	White blood cells with differential, hemoglobin, hematocrit and platelet count	24 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Exploratory outcome-ONL1204 concentration	Measurement of ONL1204 in plasma (ng/ml) after drug administration	24 weeks

Collaborators and Investigators

• Sponsor: ONL Therapeutics
• Investigators: Principal Investigator: Matthew Simunovic, M.D., Save Sight Institute, Sydney Eye Hospital, Australia

Study record dates

Study Major Dates

• Study Start (Actual): October 21, 2019
• Primary Completion (Actual): August 24, 2021
• Study Completion (Actual): August 24, 2022

Study Registration Dates

• First Submitted: December 14, 2018
• First Submitted That Met QC Criteria: December 17, 2018
• First Posted (Actual): December 19, 2018

Study Record Updates

• Last Update Posted (Actual): October 10, 2022
• Last Update Submitted That Met QC Criteria: October 7, 2022
• Last Verified: October 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Eye Diseases; Retinal Diseases; Retinal Detachment; Dissociative Disorders
• Other Study ID Numbers: ONL1204-RRD-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No