Safety and Efficacy of NPI-001 Tablets for RP Associated With Usher Syndrome

Prior treatment

• Concurrent retinal pathologies that result in vision loss or inability to fixate, including but not limited to, choroideremia, retinal vein occlusion, and neovascular age-related macular degeneration.
• Intraocular surgery within the last two months or capsulotomy within the last month.
• Use of any other investigational new drug, or participation in another clinical trial within 12 weeks before the start of study treatment.
• Use of N-acetylcysteine containing products in the previous 30 days prior to the baseline visit or unwilling to refrain from such supplements for the duration of the study.

Other illness

• History of uveitis, Coat's disease, diabetic retinopathy, glaucoma, herpes simplex of the eye, or currently has a cataract that prevents visualization of the posterior pole.
• Liver or kidney disease, cystic fibrosis, asthma or chronic obstructive pulmonary disease (COPD), history of thrombocytopenia not due to a reversible cause, or other blood dyscrasia.
• Subject has a recent history of presence of gross blood in stools.
• History of known sensitivity to N-acetylcysteine or similar thiol compounds.
• History of hypersensitivity to any medication or food resulting in systemic symptoms.
• History of cancer (other than non-melanoma skin cancer) diagnosed or requiring treatment within the past 2 years.

Lab values

• Suspected liver dysfunction determined by having alanine aminotransferase (ALT), aspartate aminotransferase (AST), or bilirubin values \> 1.5 X the upper limit of normal (ULN).
• Platelet or hemoglobin values that are below the lower limit of normal at screening (subjects with normal hemoglobin and mean corpuscular volume below the lower limit of normal should have iron studies performed to ensure that they are iron replete before taking part in the study), or neutrophils or white cell count which is above the upper limit of normal.
• Presence of more than + proteinuria on urinalysis at screening or (confirmed by abnormal albumin creatinine ratio).

Other

• Ocular:
• All edges of the EZ area in both eyes cannot be visualized at Visit 2 (Screen B).
• Unstable fixation during microperimetry in either eye at either screening or baseline visits.
  • Non-Ocular:
• Presence of hematuria on urinalysis at screening. (If hematuria is detected on urinalysis, then the specimen should be subjected to microscopy, and subject should be excluded if more than 10 X 106 red blood cells/L.) If the subject is a female in whom the hematuria may be due to menses, then the urinalysis can be repeated after a few days.
• C-reactive protein (CRP) value above 10 mg/L.
• Pregnant women or women planning to become pregnant in the next 25 months or men with partners planning to become pregnant in the next 25 months.
• Lactating women who are breast-feeding.
• A potential participant lives in the same household as a current participant in this study.
• Inability to provide blood samples, including difficulty with venous access.
• Any reason, in the opinion of the Principal Investigator, the subject should not participate.

• Male or female, age ≥18 years.
• Able to comprehend and willing to sign an informed consent form (ICF) and to adhere to the study protocol.
• Diagnosed with Usher syndrome.
• EZ zone with width ≥500 microns, which includes the fovea in each eye at Visit 2, (Screen B).
• Have at least 20 detectable points on the MAIA grid.
• On stable dose of medications associated with other conditions for at least one month.
• Both female participants of childbearing potential and male participants able to father children must have (or have a partner who has) had a bilateral oophorectomy, hysterectomy or bilateral salpingectomy; must abstain from intercourse; or must agree to practice 2 acceptable methods of contraception throughout the course of the study and 4 weeks after the last visit. Acceptable methods of contraception include hormonal contraception (i.e., birth control pills, injected hormones, dermal patch or vaginal ring), intrauterine device, barrier methods (diaphragm, condom) with spermicide, tubal ligation, or vasectomy.