A Study to Evaluate the Safety of CNTO 2476 in Patients With Advanced Retinitis Pigmentosa

A Phase I Open Label Non-comparative Study Evaluating the Safety of a Single, Unilateral, Subretinal Administration of CNTO 2476 in Advanced Retinitis Pigmentosa

The main purpose of this study is to evaluate the preliminary safety and immunogenicity (ability of an antigen to provoke immune response in the human body) of CNTO 2476, administered subretinally, in participants with advanced retinitis pigmentosa (RP; disease of the eye that leads to loss of vision and blindness) with either light perception only (LP) or hand motion (HM).

The study will be an open-label (all people know the identity of the intervention), first in human safety study. Nine adult men and women with advanced RP with LP only (first 5 participants) or not better than HM bilaterally (subsequent 4 participants) in both eyes will be enrolled. Participant 5 may have combination visual acuity of LP in the treated eye and no better than HM in the fellow eye. Treatment will proceed on a cohort basis ie, Cohort I: Participant 1; Cohort II: Participant 2; Cohort III: Participant 3 and 4; Cohort IV: Participant 5, 6, and 7; and Cohort V: Participant 8 and 9. The initial participants for each cohort must have completed at least 4 weeks of post-treatment follow-up before participants in the next cohort may be treated. There are 2 safety assessment phases in this study: the main phase approximately 12 months from the time the participant is eligible to enter the study and the long-term safety follow-up phase of 4 additional years. The total length of the participation in the study could last up to 5 years (including both the main and safety follow-up phases).

Retinitis Pigmentosa, Advanced retinitis pigmentosa (RP), CNTO 2476, Subretinal, Human umbilical tissue-derived cells (hUTC), Light perception (LP), Hand motion (HM)

Participants 1 to 4: advanced retinitis pigmentosa (RP) with light perception only (LP); Participant 5: combination visual acuity of LP in the treated eye and no better than hand motion (HM) in the fellow eye; and Participants 6 to 9: advanced RP with hand motion (HM) will receive different dose levels of CNTO 2476.

Participant 1 will receive 5.6x100000; Participants 2, 3, 5, 6, and 7 will receive 6.0x10000; Participant 4 will receive 3.0x100000; and Participants 8 and 9 will receive 1.2x100000 of CNTO 2476 as a single dose of viable cells in phosphate buffered saline (PBS) in a total volume of 100 μL injected subretinally.

This will be assessed by optical coherence tomography (OCT), fluorescein angiography (FA), fundus photography, and visual field sensitivity (FFST).

Inclusion Criteria: Confirmed diagnosis of retinitis pigmentosa that is not part of another systemic disease Vision deficit characterized by vision that is not better than either light perception (Group 1) or hand motion (Group 2) in both eyes Normal hematology and chemistry lab results Participant is suitable candidate for ophthalmologic surgery Exclusion Criteria: Other significant ophthalmologic diseases or any other ophthalmologic condition that interferes with ophthalmologic examination Women of childbearing potential Ocular hypertension Other serious medical conditions

Davis JL. The Blunt End: Surgical Challenges of Gene Therapy for Inherited Retinal Diseases. Am J Ophthalmol. 2018 Dec;196:xxv-xxix. doi: 10.1016/j.ajo.2018.08.038. Epub 2018 Sep 5.