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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Open Angle Glaucoma

Intervention / Treatment
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* Drug: ONL1204 Ophthalmic solution (Dose A)
* Drug: ONL1204 Ophthalmic solution (Dose B)
* Procedure: Sham procedure


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males and females aged ≥18 years old Able and willing to give informed consent and attend study visits Controlled intraocular pressure (IOP) (≤21 mmHg) in both eyes for all previous 3 visits before Screening and at Screening in both eyes 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 Open angle glaucoma that is progressing in the study eye HVF 24-2 at Screening with acceptable reliability standards and MD scores Exclusion Criteria: Considerations for either eye Best Corrected Visual Acuity (BCVA) at Screening of ≤64 letters (Snellen equivalent of worse than 20/50) Severe open angle glaucoma Glaucoma due to non-open angle causes Worse than mild non-proliferative diabetic retinopathy Considerations for study eye: Visual field results suggestive of another disease (eg, altitudinal field defect) Evidence of macular edema based on OCT imaging and Investigator's judgement Previous intravitreal (IVT) injections, history of retinal surgery, history of retinal laser Cataract surgery within 3 months of Screening or yttrium-aluminum-garnet capsulotomy (YAG) within 4 weeks of Screening 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: The requirement for oral carbonic anhydrase inhibitors to control intraocular pressure Severe, unstable, or uncontrolled cardiovascular, diabetic, renal, or pulmonary disease, based on Investigator's judgement Systolic blood pressure >180 mmHg or diastolic blood pressure >110 mmHg 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 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)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment Group A<br>ONL1204 Ophthalmic solution (Dose A) administered by intravitreal injection | Drug: ONL1204 Ophthalmic solution (Dose A)<br>* Liquid formulation administered by intravitreal (IVT) injection<br>|
| Experimental: Treatment Group B<br>ONL1204 Ophthalmic solution (Dose B) administered by intravitreal injection | Drug: ONL1204 Ophthalmic solution (Dose B)<br>* Liquid formulation administered by intravitreal (IVT) injection<br>|
| Sham Comparator: Treatment Group C<br>Sham procedure without penetrating the eye | Procedure: Sham procedure<br>* 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.<br>|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Progressing, Glaucoma