Safety Study of a Single IVT Injection of QPI-1007 in Chronic Optic Nerve Atrophy and Recent Onset NAION Patients

Study Overview
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Brief Summary
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This is an open-label, dose escalation, safety, tolerability and pharmacokinetic study, where active study drug (QPI-1007) will be given to all patients who participate. This study will determine whether QPI-1007 is safe when it is injected into the eye. The study will also reveal if there are any side effects of the drug and how long it takes for the body to clear the drug.

Detailed Description
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Patients will be enrolled according to one of two sets of criteria designated as Stratum I and Stratum II. Stratum I will enroll Optic Nerve Atrophy patients who meet necessary criteria. Stratum I will consist of a maximum of 6 cohorts and each cohort will enroll 3 to 6 evaluable patients. Enrollment in Stratum I is now closed. Stratum II will enroll patients diagnosed with acute Non Arteritic Anterior Ischemic Optic Neuropathy (NAION) within 28 days of symptom onset who meet necessary criteria. Stratum II will consist of a maximum of 3 cohorts and each cohort will enroll up to 10 evaluable patients. Enrollment in Stratum II is still open.

Official Title
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A Phase I Open-Label, Dose Escalation Trial of QPI-1007 Delivered by a Single Intravitreal Injection to Patients With Optic Nerve Atrophy (Stratum I) and Acute Non-Arteritic Anterior Ischemic Optic Neuropathy (NAION) (Stratum II)

Conditions
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Optic Atrophy, Non-arteritic Anterior Ischemic Optic Neuropathy

Intervention / Treatment
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* Drug: QPI-1007 at various doses


Participation Criteria
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Eligibility Criteria
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Key Stratum I (Chronic Optic Nerve Atrophy) Inclusion Criteria: Legally blind in the study eye as the result of an irreversible condition affecting the posterior segment of the eye. Clear ocular media and able to undergo adequate pupil dilation. Visual acuity and visual field in the non-study eye are better than or equal to the study eye At least 21 years old. Key Stratum I (Chronic Optic Nerve Atrophy) Exclusion Criteria: For the study eye only: history of any IVT injection or vitrectomy, vitreous hemorrhage, retinal detachment, or active inflammatory condition (e.g. conjunctivitis). For either eye: history of uveitis. Enrollment is now closed in Stratum I. Key Stratum II (Acute NAION) Inclusion Criteria: Positive diagnosis of NAION with symptom onset within 28 days prior to planned dosing with QPI-1007. Visual acuity in the study eye is between 20/40 and light perception. Clear ocular media and able to undergo adequate pupil dilation. At least 50 years old. Key Stratum II (Acute NAION) Exclusion Criteria: For the study eye only: Macular disease, retinopathy, or other eye disease limiting visual acuity; prior intraocular surgery (other than Lasik) and cataract surgery within 3 months prior to dosing; glaucoma laser surgery within 1 month prior to dosing; pain on or aggravated by eye movement; history of vitreous hemorrhage; history of retinal detachment; any active inflammatory condition (e.g. conjunctivitis); glaucoma or ocular hypertension; or intraocular pressure > 26 mmHg. For either eye: History of optic neuritis; or history of uveitis. Received any treatment for NAION prior to dosing. Any other abnormality which in the opinion of the investigator is suggestive of a disease other than NAION in the study eye only. Clinical evidence of temporal arteritis. History of collagen vascular disease or other inflammatory disease, or history of multiple sclerosis. Enrollment in Stratum II is still open.

Ages Eligible for Study
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Minimum Age: 50 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

Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: QPI-1007<br> | Drug: QPI-1007 at various doses<br>* Single Intravitreal Injection<br>* Other names: short interfering RNA;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To determine the safety, tolerability and the dose-limiting toxicities (DLTs) of QPI 1007 when administered as a single intravitreal (IVT) injection. |  | 12 Months Post-injection | 
| To assess the pharmacokinetics (PK) of QPI-1007 when administered as a single IVT injection. |  | 12 Months Post-Injection | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To determine the presence of and to describe any anatomical changes in the optic nerve head and retina observed following the administration of a single IVT injection of QPI 1007. |  | 12 Months Post-Injection | 
| To assess any changes in visual acuity and visual field observed following the administration of a single IVT injection of QPI-1007. |  | 12 Months Post-Injection | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Ocular Neuroprotection, ocular neuroprotectant, NAION, NAAION, Non-arteritic ischemic optic neuropathy, Non-arteritic anterior ischemic optic neuropathy, chronic optic nerve atrophy, optic nerve atrophy, retinal degeneration, optic neuritis, end stage glaucoma, Leber's hereditary optic neuropathy