Ensayos clínicos

Inclusion Criteria:

Subjects must receive the first study drug administration/sham procedure within 12 days of NAION symptom onset. The onset of symptoms is defined as the first day the subject reports symptoms indicative of NAION (e.g., vision loss, visual distortion, or visual disturbance) began.

• Positive diagnosis of first episode of NAION in study eye, with symptom onset within 12 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 the SITA 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.
• Subject is 50 to 80 years of age.
• 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.
• Clear ocular media and able to undergo adequate pupil dilation to allow a good fundus examination in the study eye.
• Capable of giving written informed consent.
• Willing and able to comply with the study procedures and visit schedule, including follow-up visits.
• Female subjects must be:
  • post-menopausal;
  • surgically sterile; or
  • using a highly effective means of contraception that will be continued until the Month 12 visit, with a negative pregnancy test within 24 hours prior to study drug administration/sham procedure if of childbearing potential. Male subjects with female partners of childbearing potential must agree to use a highly effective means of contraception that will be continued until the Month 12 visit.
    • Note: For the purpose of this study, post-menopausal is defined as the absence of menses for at least one year. A woman is considered to be surgically sterile if she has had a bilateral tubal ligation at least 6 months prior to administration of masked study drug, bilateral oophorectomy, or complete hysterectomy. Highly effective means of contraception include one of the following:
      • Use of hormonal contraceptives (oral, implant, transdermal patch, or injection) at a stable dose for at least 3 months prior to Day 1;
      • Use of IUD;
      • If subject is female and not use hormonal contraceptives or IUD, then all male partners throughout the study must have been vasectomized for at least 6 months prior to Day 1; or
      • If subject is male and vasectomized, he must have been vasectomized for at least 6 months prior to Day 1.

Exclusion Criteria:

• 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.
• Macular disease, proliferative (or pre-proliferative) diabetic retinopathy, or other eye disease limiting visual acuity in the study eye only.
  • Note: Retinal changes that include any or all of the following, with or without macular edema, can be classified as pre-proliferative diabetic retinopathy: multiple cotton wool spots, multiple dot and blot hemorrhages, venous abnormalities with venous loop, tortuosity and beading, intra-retinal microvascular abnormalities (IRMA). The following are examples of what would not be considered exclusionary: mild retinopathy that does not affect macular function, minor hemorrhages and few cotton wool spots.
• Prior episode of NAION in the study eye only.
• Bilateral (simultaneous) NAION.
• NAION secondary to acute blood loss (e.g., due to surgery, trauma, or spontaneous hemorrhage) or immediately following any surgery
• 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.
• 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.
• Pain on eye movement in either eye.
• History of vitrectomy in the study eye only.
• History of vitreous hemorrhage in the study eye only.
• History of retinal detachment in the study eye only.
• History of optic neuritis in either eye.
• History of uveitis in either eye.
• Any active inflammatory condition in the study eye only (e.g., scleritis, uveitis).
  • Note: Mild blepharitis is not exclusionary.
• Any active infectious condition (e.g., conjunctivitis) in either eye.
• Glaucoma or ocular hypertension in the study eye only.
• Intraocular pressure (IOP) greater than 25 mmHg on Day 1 prior to masked study drug administration in the study eye only.
• Present use of drugs known to cause optic nerve or retinal toxicity at Day 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 trial.
• Any other abnormality that, in the opinion of the Investigator, is suggestive of a disease other than NAION in the study eye only.
  • Note: Previously established acquired significant dyschromatopsia, non-altitudinal visual field loss in the study eye, large cup-to-disc ratio in either eye, greater than 0.6 in the unaffected eye, or Uhthoff phenomenon does not necessarily exclude the subject; however, the Investigator should evaluate these signs and symptoms in the context of whether they are suggestive of a disease other than NAION in the study eye. If they are, then these subjects should be excluded. If the Investigator’s opinion is that they are just coincidental findings, then the subject may be eligible. Inconclusive cases can be discussed with the Medical Monitor.
• Any history or current evidence of a medical condition (systemic or ophthalmic disease, metabolic dysfunction, physical examination finding or clinical laboratory finding), concomitant therapy, or previous incisional or laser surgery in the study eye only, that, in the opinion of the iInvestigator, may preclude the safe administration of study drug, adherence to the scheduled study visits, or safe participation in the study.
• Clinical evidence of temporal arteritis based on ANY of the following:
  • Symptoms or signs: Two or more of the following should be present; previous episodes of transient visual loss leading up to persistent visual loss, pallid disc edema, headache, proximal myalgias, anorexia, weight loss, fever, malaise. Presence of jaw claudication, or ear pain, or scalp tenderness, or temple tenderness overlying the temporal arteries alone is enough to exclude the subject; OR
  • C-reactive protein (CRP) greater than twice the institutional upper limit of normal (ULN); OR
  • Abnormal Erythrocyte Sedimentation Rate (ESR). "Abnormal" is defined as greater than age/2 for males or (age+10)/2 for females, in mm/hr;
  • Diffuse pale swelling of the optic disc.
• Bilateral (simultaneous) disc swelling.
• History of amiodarone use in the 12 months prior to Day 1/Randomization visit.
• Active (i.e., requiring steroid or immunomodulary therapy) collagen vascular disease or other inflammatory disease, such as: ankylosing spondylitis, dermatomyositis, polyarteritis nodosa, psoriatic arthritis, rheumatoid arthritis, scleroderma, systemic lupus erythematosus, and giant cell arteritis.
• History of multiple sclerosis.
• Pregnant or lactating.
• History of active malignancy within the last 5 years; however, non-facial, basal cell carcinoma is allowed if it has been adequately treated.
• History of myocardial infarction within the last 6 months.
• Participating in a concurrent interventional study with the last intervention occurring within 30 days prior to Day 1.
• Any intravitreal injection within 3 months prior to Day 1 in the study eye only.
  • Note: Concomitant intravitreal therapy in the fellow eye is permitted, but cannot be administered within seven days of treatment with masked study drug.
• Previous enrollment in this current trial.
• Previous participation in any clinical study investigation with QPI-1007 Injection.
• Planned use of PDE5 inhibitor during study.