We initiated this project at the NEI in fiscal year 2014 as a site in the phase 2 clinical trial (14-EI-0078) testing CNTF for macular telangiectasia (MacTel). We met the accrual goal at the NEI site and study analysis has been completed, with publication of the primary results in press. The trial met its primary endpoint, with eyes receiving sham treatment showing 31% greater progression of neurodegeneration than the CNTF-treated eyes using an en face OCT measure of change in area of outer retinal disruption, with difference in mean area of photoreceptor loss of 0.05 0.03 mm2 (p = 0.04) at 24 months. The phase 2 protocol has been terminated following completion. Participants in the phase 2 trial were enrolled in an extension study (17-EI-0136) to study effects of the CNTF implant at years 3, 4, 5, and 6, and follow up continues for site participants in this protocol. In fiscal year 2018, we were activated as a site in the phase 3 clinical trial (18-EI-0055) testing CNTF (NT-501, Renexus) for MacTel. We have enrolled three participants, and accrual continues. A summary of the phase 3 trial is listed below: Objective: To determine the efficacy and safety of Renexus, an intraocular encapsulated cell implant secreting ciliary neurotrophic factor (CNTF), for the treatment of macular telangiectasia (MacTel) type 2. Study Population: This study is open to all persons with confirmed MacTel Type 2 who meet the Inclusion/Exclusion Criteria. Approximately 112 participants across all sites in this multicenter study will undergo study intervention. The NEI site will screen up to 12 participants, with a goal of offering study intervention to up to 6 participants. Design: This is a phase III, multi-center, single-masked, sham-controlled study of approximately 112 study participants with MacTel Type 2. Each participant will contribute a single study eye. Participants will be randomized (1:1) to receive the Renexus implant surgery or sham surgery in the study-eligible eye. All participants will be followed through 24 months. All participants will have a screening period of up to 30 days, and surgery/sham will occur within 4 weeks after completing screening. Study eyes will receive the Renexus implant surgery or sham surgery on Day 0 and will be assessed on Day 1, Week 1 ( 2 days), Month 6 ( 4weeks), Month 12 (4 weeks), Month 16 ( 4 weeks), Month 20 ( 4 weeks) and Month 24 ( 4 weeks). A telephone contact will be made at Month 1 ( 1 week), and Month 3 ( 1 week). Outcome Measures: Primary Outcome: The primary efficacy endpoint will be the rate of change (slope) in the area of ellipsoid zone disruption (area of photoreceptor inner segment/outer segment signal loss) from baseline over 24 months as measured by en face imaging by SD-OCT in the study eye. Secondary Outcomes: Secondary outcomes to investigate efficacy include the following, comparing participants receiving Renexus with those receiving sham intervention: Mean change in aggregate sensitivity of microperimetry within the area of ellipsoid zone disruption from baseline through 24 months. Mean change in reading speed from baseline through 24 months. Mean change in the NEI Visual Function Questionnaire near activities subscale score from baseline through 24 months. Secondary outcomes to investigate safety include the following: Number and proportion of participants with a loss in best-corrected visual acuity of >15 or more letters from baseline in the study eye using ETDRS testing.
