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

Patients will be enrolled according to one of two sets of criteria designated as Stratum I and Stratum II.

1. 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.
2. 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.

• QPI-1007 at various doses (Drug), also known as QPI-1007, siRNA, small interfering RNA, short interfering RNA: Single Intravitreal Injection

Primary outcomes

• 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 outcomes

• 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]

Sex: All, ages: 50 Years to any

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.

• Rabia Ozden, MD, Study director, Quark Pharmaceuticals