A Study of Encapsulated Cell Technology (ECT) Implant for Patients With Late Stage Retinitis Pigmentosa

A Phase II/III Study of Encapsulated Human NTC-201 Cell Implants Releasing Ciliary Neurotrophic Factor (CNTF) for Participants With Retinitis Pigmentosa Using Visual Acuity as the Primary Outcome

The purpose of this study is to look at the safety and effectiveness of CNTF implants on vision in persons with retinitis pigmentosa, Usher type II & III, and Choroideremia. This research is being done because there are no effective therapies for people with these retinal degenerations. They are genetic disorders that affect our ability to see at night, and later cause tunnel vision and loss of central vision. Retinal degenerations affect the retina, a light sensitive layer of cells in the back of the eye. Slowly over time, these cells die and cause permanent loss of vision.

The implant is a small capsule that contains human retinal pigment epithelium cells. These cells have been given the ability to make CNTF and release it through the capsule membrane into the surrounding fluid. This study will look at the effect of the implant on vision loss by retinitis pigmentosa, Usher type II & III, and Choroideremia. In this study, two different CNTF dose levels will be used: a high dose and a low dose in one eye, as well as a sham (or placebo) surgery in the other eye.

This study will involve about 16 visits over 1½ years for specific tests of the participant's vision and health. These visits may include visual exams, blood draw for laboratory testing, brief medical history and exam, and occasionally a questionnaire (survey), in addition to the visit for the surgical procedures. The primary effectiveness outcome for this study will be a visual acuity score one year after the implant surgery. There will be about 13 centers participating in this study, and up to 60 people enrolled across the US. Each participant joining the study who has completed initial screening will then be scheduled to have a brief surgical procedure performed on each eye, one of which will include a very small cell-filled implant. Follow-up visits for repeat assessments will be required regularly to determine if the implant being tested is safe and effective for use to treat RP.

Inclusion Criteria:

1. Participant was older than 18, but less than 68 years of age.

2. Participant understood and signed the informed consent. If the participant's vision was impaired to the point where he/she could not read the informed consent document, the document would be read to the participant in its entirety.

3. Females of childbearing potential (women with last menses <1 year prior to screening) agreed to use an effective form of birth control from study onset until they completed the 18-month study visit.

4. Participant was medically able to undergo ophthalmic surgery for the NT-501 device.

5. Participant's clinical diagnosis was consistent with retinal degeneration in the set of retinitis pigmentosa (RP) dystrophies characterized by the following features:

   1. clinical evidence of progressive photoreceptor cell dysfunction and degeneration of the outer retina.
   2. intraretinal bone-spicule'-like pigment observed in clinical examination (not necessarily applicable to choroideremia).
   3. peripheral visual field constriction documented on standard testing.
   4. symptomatic night blindness.
   5. reduction of both rod and cone electroretinogram (ERG) responses. Individuals diagnosed with Retinitis Pigmentosa, Usher Syndrome Type 2 or Type 3 (without profound deafness or cochlear implant) or with Choroideremia (CHM) and who met the inclusion criteria were considered as potential candidates for this study. A maximum of 5 Usher Syndrome Type 2 or Type 3 and a maximum of 5 Choroideremia participants could be enrolled in this trial.

6. Each eye had a visual acuity score of at least 24 (20/320) and no more than 63 (20/63) letters.

7. Each eye had an ERG amplitude reduced below the 95% limit of normal (CI) per site by Full Field 28-32 Hz flicker.

Exclusion Criteria:

1. Participant was medically unable to comply with study procedures or follow-up visits.

2. Participant had glaucoma (defined as independent optic atrophy causing vision loss), irrespective of whether it was currently treated or untreated.

3. Participant had classic syndromic RP.

4. Participant had optic nerve atrophy beyond modest pallor, primary cone-rod dystrophy, unilateral bulls-eye maculopathy, cystoid maculopathy as judged by OCT reading center, or other retinal dystrophy.

5. Participant who had any of the following lens opacities: cortical opacity > standard 3, posterior subcapsular opacity > standard 3, or a nuclear opacity > standard 3 as measured on the AREDS clinical lens grading system.

6. Participant had chronic requirement (e.g., > or =4 weeks at a time) for ocular medications or has disease(s) that in the judgment of the examining physician were vision threatening, toxic to the lens, retina, or optic nerve or might affect the primary outcome.

7. Participant had a requirement of acyclovir and/or related products during study duration.

   To be eligible for this study, the participant must have discontinued use of these products prior to enrollment and must not continue with the products until after they had completed the study.

8. Participant had evidence of corneal opacification or lack of optical clarity.

9. Participant had undergone lens removal in the last 3 months, with or without intra-ocular lens implantation, or had undergone intra-ocular lens replacement within 6 months prior to enrollment.

10. Participant was receiving systemic steroids or other immunosuppressive medications.

11. Participant had undergone LASIK surgery or other refractive surgery for either eye in less than 6 months prior to screening.

12. Participant was currently participating in or had participated in any other clinical trial of a drug by ocular or systemic administration within the last 6 months.

13. Participant had previous exposure to an intra-ocular device or implant into the eye (excluding intra-ocular lens).

14. Participant had uveitis or other retinal inflammatory disease.

15. Participant was receiving oral or other insulin treatment for diabetes.

16. Participant who had a history of myocardial infarction within the last 12 months.

17. Participant was pregnant or lactating.

18. Participant was considered immunodeficient or had a known history of HIV. A laboratory test for HIV was performed, and a positive result was also an exclusion criterion.

19. Participant with a history of ocular herpes zoster.

20. Participant was on chemotherapy.

21. Participant had a history of malignancy, except study participants having cancer treated successfully ≥5 years prior to inclusion in the trial.

22. Participant with severe hearing disabilities in both ears.

23. Participant with diabetic retinopathy in either eye.

24. Participant had history of retinal detachment in either eye.

25. Participant had been diagnosed and treated for amblyopia as an infant.

26. Participant with a history of Pars Plana Vitrectomy.