Nitisinone for Type 1B Oculocutaneous Albinism

Objective: The primary objective of this study is to evaluate oral nitisinone as a treatment that improves ocular pigmentation in adult participants with oculocutaneous albinism, type 1B (OCA1B). Secondary objectives of this study are to determine whether the selected outcome measures are robust enough to use in a larger trial and to assess whether oral nitisinone improves visual function, skin pigmentation, and hair pigmentation in participants with OCA1B. Study Population: Five participants with OCA1B will be enrolled initially. However, up to an additional three participants may be enrolled to account for participants who withdraw from the study for any reason before the Month 12 visit. Design: In this pilot, phase 1/2, single-site, prospective, open label trial, participants will receive 2 mg of oral nitisinone daily for at least one year, and they will be followed for at least 18 months. Ocular and non-ocular data will be collected at least every three months, with the first follow-up visit occurring three months after the final baseline visit. Participants will be required to have at least 8 outpatient visits at the NEI clinic over a period of 18 months. This study has a common termination date and therefore may continue for up to four years. Outcome Measures: The primary outcome for the study is the absolute mean change in iris pigmentation on an 8-point scale at 12 months as compared to baseline. Participants left and right eyes will be analyzed. The absolute mean change in iris pigmentation for each eye on an 8-point scale at 3, 6 and 9 months compared to baseline will be assessed as secondary outcomes. Other secondary outcomes include the absolute and percent change in semi-quantitative iris pigmentation on image analysis; the absolute change in electronic visual acuity (EVA) for each eye and binocular vision; the absolute change in contrast sensitivity without glare, with medium glare, and with high glare for binocular vision; the absolute change in full-field ERG measures for each eye; and the absolute and percent change in melanin content in skin using skin reflectometry at 3, 6, 9 and 12 months as compared to baseline; Qualitative changes in hair, skin, and fundus pigmentation at 3, 6, 9 and 12 months as compared to previous visit will be assessed. The absolute and percent change in hair melanin will also be assessed at 12 months as compared to baseline. The number and severity of adverse events and the number of withdrawals will be assessed as safety outcomes.