NAION typically presents as an abrupt, painless monocular vision loss. Visual loss varies widely, ranging from visual field loss only to complete blindness. The neuronal degeneration process in NAION is thought to occur as primary retinal ganglion cell (RGC) axonal and glial damage from ischemia
Conditions
Interventions
Product Code: QPI-1007 30mg/ml
Pharmaceutical Form: Injection
CAS Number: 1231741-17-5
Current Sponsor code: QPI-1007
Other descriptive
Sponsors
Quark Pharmaceuticals Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1.Positive diagnosis of first episode of NAION in the study eye, with symptom onset within 14 days prior to Day 1. The NAION diagnosis requires all of the following: • Disc edema (observed and documented at the study site) • Visual field defects in the study eye consistent with optic neuropathy and mean deviation worse than -3.0 dB on Humphrey standard automated perimetry using theSITA standard 24-2 testing protocol • Relative afferent pupillary defect (unless the contralateral eye had previous NAION or other optic nerve or retinal disease that is not an exclusion criterion) • OCT image and VF pattern compatible with the diagnosis of NAION, as determined by a Central Reading Center. 2.-Subject is 50 to 80 years of age. 3.-Best-corrected visual acuity score in the study eye is better than or equal to 15 letter score, measured using the ETDRS visual acuity protocol at Day 1 prior to study drug administration/sham procedure 4.-Clear ocular media and able to undergo adequate pupil dilation to allow a good fundus examination in the study eye. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 164 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 656
Exclusion criteria
Exclusion criteria: 1. Present use or history of any treatment for the current episode of NAION, including systemic steroids or brimonidine. Traditional Chinese herbal medicine taken for the treatment of the current episode of NAION should be discontinued. 2. Macular disease, proliferative (or pre-proliferative) diabetic retinopathy, or other eye disease limiting visual acuity in the study eye only, as determined either by the site investigator or at the Reading Center. 3. Prior episode of NAION in the study eye only. 4. Bilateral (simultaneous) NAION 5. NAION secondary to acute blood loss (e.g., due to surgery, trauma, or spontaneous hemorrhage) or immediately following any surgery 6. Prior incisional or laser intraocular surgery in the study eye at any time. Note: The following subset of surgeries are allowed within the windows specified for each surgery type: • Corneal laser surgeries (e.g., laser-assisted in situ keratomileusis) performed more than 1 month prior to Day 1; • Laser capsulotomy performed more than 1 week prior to Day 1; • Cataract surgery performed more than 3 months prior to Day 1; • Glaucoma laser surgery (i.e., laser iridotomy, laser iridoplasty) performed for narrow anterior chamber angle (not for ocular hypertension or glaucoma) performed more than 1 month prior to Day 1; • Retinal laser surgeries for small peripheral retinal tears in the study eye performed more than 1 month prior to Day 1. 7. Any of the following Visual Field exclusions at Screening Visit (inconclusive visual fields should be sent to the Reading Center for adjudication) in the study eye: • Less than 3 adjacent abnormal points (>0.5% significance) on the pattern deviation map and the total deviation map • Temporal or nasal field loss that respects vertical midline • Homonymous binocular field loss (other than bilateral altitudinal in a subject with prior NAION) • Heteronymous binocular field loss that is bitemporal • Only abnormality on the field is an enlarged blind spot 8. Pain on eye movement in either eye. 9. History of vitrectomy in the study eye only 10. History of vitreous hemorrhage in the study eye only. 11. History of retinal detachment in the study eye only 12. History of optic neuritis in either eye. 13. History of uveitis in either eye. 14. Any active inflammatory condition in the study eye only (e.g., scleritis, uveitis). Note: Mild blepharitis is acceptable. 15. Any active infectious condition (e.g., conjunctivitis) in either eye. 16. Glaucoma or ocular hypertension in the study eye only. 17. Intraocular pressure (IOP) greater than 25 mmHg on Day 1 prior to masked study drug administration in the study eye only. 18. Present use of drugs known to cause optic nerve or retinal toxicity atDay 1/Randomization, such as: chloroquine or hydroxychloroquine, ethambutol, Vigabatrin. Subjects who need to be prescribed any of these drugs during the course of the study will be discontinued from the
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: 1. To assess the safety and tolerability of QPI-1007 IVT injections in subjects with recent-onset NAION. 2. To determine the effect on visual function of QPI-1007 IVT injections in subjects with recent-onset NAION. ;Secondary Objective: To evaluate the structural changes in the peripapillary retinal nerve fiber layer (RNFL) and ganglion cell layer following administration of QPI-1007 in subjects with recent-onset NAION.; Primary end point(s): • The primary endpoint is the proportion of subjects who lose 15 letters or more in best corrected visual acuity (BCVA) score from Baseline (Day 1/Randomization) to Month 6, as measured by ETDRS visual acuity protocol in the study eye. The primary endpoint population will include subjects who are randomized within 12 days of the onset of NAION symptoms. ;Timepoint(s) of evaluation of this end point: The proportion of subjects losing at least 15 letters in BCVA will be compared among each QPI-1007 treatment group and the control group using the exact multiple logistic regression test. Separate comparisons will be made for the four active treatment groups vs. the sham control group. The analysis will be performed on the mITT population randomized within 12 days of the onset of NAION symptoms. | — |
Secondary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: For the analysis of the key secondary efficacy endpoints, a step-down sequential testing procedure will be used to control the overall type 1 error at 0.05. With this procedure, the primary and two key secondary efficacy endpoints will be evaluated for statistical significance based on a pre-specified sequence for interpretation. 1. Mean change from Day 1 to Month 12 in BCVA score, as measured by ETDRS visual acuity protocol in the study eye. 2. Mean change of visual field mean sensitivity from Day 1 to Month 12, as assessed by Humphrey standard automated perimetry using a full-threshold strategy and a size V stimulus in the study eye. ; Secondary end point(s): 1. The proportion of subjects who lose 15 letters or more in best corrected visual acuity (BCVA) score from Baseline (Day 1) to Month 6, as measured by ETDRS visual acuity protocol in the study eye. This analysis will be conducted in all subjects who are randomized. 2. Mean change from Day 1 to Month 6 in BCVA letter score, as measured by ETDRS visual acuity protocol in the study eye. This analysis will be conducted in subjects: 2.1 who are randomized within 12 days of the onset of symptoms 2.2 who are randomized. 3. Mean change of visual field mean sensitivity from Day 1 to Month 6, as assessed by Humphrey standard automated perimetry using a full-threshold strategy and a size V stimulus in the study eye. This analysis will be conducted in subjects: 3.1 who are randomized within 12 days of the onset of symptoms. 3.2 who are randomized. | — |
Countries
Australia, China, Germany, India, Israel, Italy, Singapore, United States
Contacts
Public ContactClinical Operations
Quark Pharmaceuticals Inc.
Outcome results
None listed