Oral N-acetylcysteine for Retinitis Pigmentosa

Prior treatment

• Uncontrolled blood pressure (defined as systolic \> 180 and/or diastolic \> 100 mmHg while at rest) at screening. If a patient's initial measurement exceeds these values, a second reading may be taken 30 or more minutes later. If the patient's blood pressure must be controlled by antihypertensive medication, the patient may become eligible if medication is taken continuously for at least 30 days.
• Participation in an investigational study that involves treatment with any drug or device within 6 months of screening
• Any prior macular laser photocoagulation
• Intraocular surgery within 3 months prior to screening
• High myopia with spherical equivalent refractive error \> 8 diopters. If an eye has had cataract surgery or refractive surgery, a pre-operative refractive error spherical equivalent \> 8 diopters is an exclusion
• Any concurrent ocular condition that might affect interpretation of results

Other illness

• Active cancer within the past 12 months, except for appropriately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, or prostate cancer with Gleason score ≤ 6 and stable prostate specific antigen for \> 12 months
• Renal failure requiring renal transplant, hemodialysis, peritoneal dialysis, or anticipated to require hemodialysis or peritoneal dialysis during the study
• Liver disease, cystic fibrosis, asthma, or chronic obstructive pulmonary disease (COPD), history of thrombocytopenia not due to a reversible cause or other blood dyscrasia
• Cerebrovascular accident or myocardial infarction within 6 months of screening
• Known history of allergy to NAC
• Sucrase-isomaltase insufficiency
• HIV or hepatitis B infection
  • Ocular Exclusion Criteria
• Glaucoma or other optic nerve disease causing visual field loss or reduced visual acuity
• Any retinal disease other than RP causing reduction in visual field or visual acuity
• History of uveitis in either eye

Lab values

• History of other disease, physical examination finding, or clinical laboratory finding giving reasonable suspicion that oral NAC may be contraindicated or that follow up may be jeopardized
• Glucose-galactose malabsorption
• Abnormal laboratory value including the value of alanine aminotransferase (ALT), aspartate aminotransferase (AST), or bilirubin being greater than 1.5 x the upper limit of normal

Other

• General Exclusion Criteria
• Three relatives already enrolled in study
• Pregnant, breast feeding, or intending to become pregnant during the study treatment period. Women of childbearing potential who have not had tubal ligation must have a urine pregnancy test at screening.
• Having taken NAC in any form in the past 4 months
• Phenylketonuria
• Fructose intolerance
• Any major abnormal findings on blood chemistry, hematology, and renal function lab tests that in the opinion of the Site Investigator and/or the Study Chair makes the candidate not suitable to participate in the trial
• Evidence of cone-rod dystrophy or pattern dystrophy including focal areas of atrophy or pigmentary changes in the central macula
• Cystoid spaces involving the fovea substantially reducing vision
• Intra ocular pressure \>27 mm Hg from two measurements. If a patient's initial measurement exceeds 27 mm Hg, a second reading must be taken.

• General
• Ability and willingness to provide informed consent
• Age ≥ 18 and ≤65 years at time of signing Informed Consent Form
• Ability and willingness to comply with the study protocol and to participate in all study visits and assessments in the investigator's judgement
• For candidates of childbearing potential: willingness to use a method of contraception
• Agreement not to take supplements other than vitamin A
  • Ocular Inclusion Criteria
• Both eyes must exhibit the RP phenotype with evidence of loss of night vision, gradual constriction of visual fields, and maintenance of visual acuity;
• In addition, an eye must meet the following criteria to be included in the study:
• Gradable EZ on a horizontal SD-OCT scan through the fovea center with width ≤ 8000 µm and ≥1500 µm and with well-defined truncation at both the nasal and temporal sides;
• BCVA ≥ ETDRS letter score of 61 (20/60 Snellen equivalent);
• Sufficiently clear ocular media and adequate pupillary dilation to allow good quality images sufficient for analysis and grading by central reading center.