A Phase 1b Study of ONL1204 Ophthalmic Solution in Patients with Progressing Open Angle Glaucoma

A Phase 1b Multicenter, Randomized, Single-Masked, Sham-Controlled Study of the Safety and Tolerability of ONL1204 Ophthalmic Solution in Patients with Progressing Open Angle Glaucoma

The purpose of this study is to demonstrate the safety and tolerability of ONL1204 Ophthalmic Solution in patients with progressing open angle glaucoma.

ONL1204 Ophthalmic Solution is a first-in-class inhibitor of fragment apoptosis stimulator (Fas) receptor-mediated cell death that has demonstrated protection of multiple retinal cell types in numerous preclinical models of retinal disease. Apoptosis of retinal ganglion cells is associated with progressive glaucoma. Nonclinical data on ONL1204 Ophthalmic Solution suggest that ONL1204 Ophthalmic Solution may inhibit the cell death pathways in these cells.

Study Overview

• Status: Completed
• Conditions: Open Angle Glaucoma
• Intervention / Treatment: Drug: ONL1204 Ophthalmic solution (Dose A); Drug: ONL1204 Ophthalmic solution (Dose B); Procedure: Sham procedure

• Study Type: Interventional
• Enrollment (Actual): 25
• Phase: Phase 1

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Albury, New South Wales, Australia, 2640
      • Albury Eye Clinic Wodonga
    • Hurstville, New South Wales, Australia, 2220
      • Sydney Eye Surgeons
    • Parramatta, New South Wales, Australia, 2150
      • Personaleyes
    • Sydney, New South Wales, Australia, 2000
      • Eye Associates
  • Victoria
    • Armadale, Victoria, Australia, 3143
      • Armadale Eye Clinic
    • Fitzroy, Victoria, Australia, 3065
      • Melbourne Eye Specialists
    • Gladstone Park, Victoria, Australia, 3403
      • North West Eye Specialists
    • Melbourne, Victoria, Australia, 3002
      • Centre for Eye Research Australia (CERA)
    • Waverley, Victoria, Australia, 3150
      • Waverely Eye Clinic
• New Zealand
  • Wellington, New Zealand, 6011
    • Capital Eye Specialists
  • Auckland
    • Remuera, Auckland, New Zealand, 1050
      • Eye Institute Limited

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Males and females aged ≥18 years old
2. Able and willing to give informed consent and attend study visits
3. Controlled intraocular pressure (IOP) (≤21 mmHg) in both eyes for all previous 3 visits before Screening and at Screening in both eyes
4. Prior to screening, 3 or more Humphrey Visual Field (HVF) tests (with acceptable reliability standards) or 3 or more Optical Coherence Tomography (OCT) studies of the study eye on record
5. Open angle glaucoma that is progressing in the study eye
6. HVF 24-2 at Screening with acceptable reliability standards and MD scores

Exclusion Criteria:

Considerations for either eye

1. Best Corrected Visual Acuity (BCVA) at Screening of ≤64 letters (Snellen equivalent of worse than 20/50)
2. Severe open angle glaucoma
3. Glaucoma due to non-open angle causes

4. Worse than mild non-proliferative diabetic retinopathy

   Considerations for study eye:

5. Visual field results suggestive of another disease (eg, altitudinal field defect)
6. Evidence of macular edema based on OCT imaging and Investigator's judgement
7. Previous intravitreal (IVT) injections, history of retinal surgery, history of retinal laser
8. Cataract surgery within 3 months of Screening or yttrium-aluminum-garnet capsulotomy (YAG) within 4 weeks of Screening

9. Anticipated need for surgical or procedural intervention for glaucoma, cataract, posterior capsular opacity, refractive error, or retinal conditions during the study

   Other general exclusion criteria:

10. The requirement for oral carbonic anhydrase inhibitors to control intraocular pressure
11. Severe, unstable, or uncontrolled cardiovascular, diabetic, renal, or pulmonary disease, based on Investigator's judgement
12. Systolic blood pressure >180 mmHg or diastolic blood pressure >110 mmHg
13. Women who are pregnant, breastfeeding, or contemplating pregnancy during the study period and men who are contemplating contributing sperm for a biologic child during the study period
14. Participation in other ophthalmic clinical trials or use of any other investigational drugs or devices in either eye or systemically for 3 months before Screening (Visit 1)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment Group A; ONL1204 Ophthalmic solution (Dose A) administered by intravitreal injection	Drug: ONL1204 Ophthalmic solution (Dose A); Liquid formulation administered by intravitreal (IVT) injection
Experimental: Treatment Group B; ONL1204 Ophthalmic solution (Dose B) administered by intravitreal injection	Drug: ONL1204 Ophthalmic solution (Dose B); Liquid formulation administered by intravitreal (IVT) injection
Sham Comparator: Treatment Group C; Sham procedure without penetrating the eye	Procedure: Sham procedure; A sham procedure looks like a real injection into the eye but does not penetrate the eye and it does not have any study drug. The procedure is done by touching the eye surface with a syringe without a needle.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety and Tolerability of ONL1204 as assessed by AE reporting and clinical evaluations	Adverse event reporting, ophthalmic examination to evaluate the anterior and posterior segments of the eye, best-corrected visual acuity, intraocular pressure, electroretinogram, vital signs, clinical laboratory evaluations, and ophthalmic imaging results	up to 39 weeks

Collaborators and Investigators

• Sponsor: ONL Therapeutics

Publications and helpful links

Helpful Links

• ONL Therapeutics corporate website

Study record dates

Study Major Dates

• Study Start (Actual): May 2, 2022
• Primary Completion (Actual): April 9, 2024
• Study Completion (Actual): April 9, 2024

Study Registration Dates

• First Submitted: December 6, 2021
• First Submitted That Met QC Criteria: December 6, 2021
• First Posted (Actual): December 16, 2021

Study Record Updates

• Last Update Posted (Actual): October 29, 2024
• Last Update Submitted That Met QC Criteria: October 26, 2024
• Last Verified: October 1, 2024

More Information

Terms related to this study

• Keywords: Glaucoma; Progressing
• Additional Relevant MeSH Terms: Eye Diseases; Ocular Hypertension; Glaucoma; Glaucoma, Open-Angle; Pharmaceutical Solutions; Ophthalmic Solutions
• Other Study ID Numbers: ONL1204-OAG-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
• product manufactured in and exported from the U.S.: No