Retinal Imaging in CNTF -Releasing Encapsulated Cell Implant Treated Patients for Early-stage Retinitis Pigmentosa

NCT01530659 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: AOSLO-CNTF-FFB-01FD-R-004100-01A1
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 1

Brief Summary

This clinical trial is a single-site, 30 patient study for participants who have early stage retinitis pigmentosa, or Usher syndrome (type 2 or 3). Funding Source - FDA OOPD and Foundation Fighting Blindness.

Conditions

Retinitis Pigmentosa; Usher Syndrome Type 2; Usher Syndrome Type 3

Keywords

Retinitis pigmentosa; Usher syndrome type 2; Usher syndrome type 3; Cone photoreceptor; Vision; Blind

Outcome Measures

Primary Outcomes (1)

• Mean Change in Cone Spacing in Arcminutes (Z Score) of 2 Baseline Values Were Compared With Measurements Obtained at Post-op Month 36

  Average of cone spacing (nearest neighbor distance) at all regions of interest with at least 50 contiguous unambiguous cones identified over the central 5.7 degrees of the macula using confocal AOSLO at two baseline visits within each eye. Cone spacing measures were converted to Z scores based on normal mean values at similar distances from the fovea from a database of 27 age-similar normal eyes. The mean of 2 baseline cone spacing Z-score values were subtracted from the cone spacing Z score values obtained at post-op month 36 A Z-score of 0 represents the mean cone spacing value at the distance from the fovea measured from 27 healthy subjects. A Z-score greater than +2 represents an abnormally increased cone spacing value at the distance from the fovea where the measurement was performed. This suggests fewer cones are present than normal at that location.

  Post-op Month 36

Secondary Outcomes (1)

• Difference in logMAR Visual Acuity Change Between CNTF- and Sham Treated Eyes

  Post-op Month 36

Study Arms (2)

NT-501

EXPERIMENTAL

Encapsulated cell therapy that delivers ciliary neurotrophic factor to the retina

Drug: NT-501

Sham

SHAM COMPARATOR

Sham surgery

Procedure: Sham

Interventions

NT-501 DRUG

Study participants will undergo surgery to have an NT-501 Encapsulated Cell Therapy implant placed into the study eye.

Also known as: CNTF, Encapsulated Cell Therapy, ECT

NT-501

Sham PROCEDURE

Non-penetrating sham procedure to mimic implant procedure in the other eye.

Sham

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Participant must be between 18 and 55 years of age.
• Participant must have a diagnosis of retinitis pigmentosa or Usher Syndrome type 2 or 3 (without profound deafness or cochlear implants).
• Participant must understand and sign the protocol informed consent. If the participant's vision is impaired to the point where he/she cannot read the informed consent document, the document will be read to the participant in its entirety.
• Best-corrected visual acuity must be no worse than 20/63 (at least 59 letters).
• Participants must have clear natural lenses.
• Participants must have less than 6 diopters myopia.
• Participants must be medically able to undergo ophthalmic surgery for the NT-501 device insertion and able to undergo all assessments and tests associated with the protocol.
• Females of childbearing potential (women with last menses \<1 year prior to screening) must agree to use an effective form of birth control from study onset until they complete the study.
• Participants must have reproducible baseline AOSLO image at 2 baseline imaging sessions with quality suitable to identify a minimum of 7 regions of interest (ROIs) at which reliable cone spacing and/or density measures can be made over the central 5.7 degrees.
• Participants must have interocular symmetry of disease severity as measured by cone spacing, with a difference of less than 2 standard deviations in average cone spacing z-scores at the selected ROIs between the 2 eyes.
• Participant's clinical diagnosis must be consistent with retinal degeneration in the set of retinitis pigmentosa (RP) dystrophies.

You may not qualify if:

• Participant is medically unable to comply with study procedures or follow-up visits.
• Participant who has 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; or participant is pseudophakic or aphakic.
• Participant has history of corneal opacification or lack of optical clarity.
• Participant has undergone LASIK surgery or other refractive surgery for either eye.
• Participant has nystagmus.
• Participant has greater than 6 diopters myopia.
• Participant has cystoid macular edema with cysts present within 4 degrees of the foveal center that prevent acquisition of at least 7 regions of interest with clear images of cone photoreceptors.
• Participant has fewer than 7 regions of interest (ROIs) present on 2 baseline AOSLO image montages.
• Participant has retinal vascular disease such as diabetic retinopathy or prior retinal vascular occlusive disease.
• Participant has chronic requirement (e.g., ≥4 weeks at a time) for ocular medications or has disease(s) that in the judgment of the examining physician are vision threatening, toxic to the lens, retina, or optic nerve or may affect the primary outcome.
• Participant has a requirement of acyclovir and/or related products during study duration. To be eligible for this study, the participant must discontinue use of these products prior to enrollment and must not continue with the products until after they have completed the study.
• Participant is receiving systemic steroids or other immunosuppressive medications.
• Participant is currently participating in or has participated in any other clinical trial of a drug by ocular or systemic administration within the last 6 months.
• Participant has previous exposure to an intra-ocular device or implant into the eye (excluding intra-ocular lens).
• Participant has uveitis or other retinal inflammatory disease.

Sponsors & Collaborators

• Neurotech Pharmaceuticals: lead
• University of California, San Francisco: collaborator

Study Sites (1)

University of California, San Francisco

San Francisco, California, 94143, United States

Location

Related Publications (3)

• Duncan JL, Zhang Y, Gandhi J, Nakanishi C, Othman M, Branham KE, Swaroop A, Roorda A. High-resolution imaging with adaptive optics in patients with inherited retinal degeneration. Invest Ophthalmol Vis Sci. 2007 Jul;48(7):3283-91. doi: 10.1167/iovs.06-1422.

  PMID: 17591900 BACKGROUND

• Sieving PA, Caruso RC, Tao W, Coleman HR, Thompson DJ, Fullmer KR, Bush RA. Ciliary neurotrophic factor (CNTF) for human retinal degeneration: phase I trial of CNTF delivered by encapsulated cell intraocular implants. Proc Natl Acad Sci U S A. 2006 Mar 7;103(10):3896-901. doi: 10.1073/pnas.0600236103. Epub 2006 Feb 27.

  PMID: 16505355 BACKGROUND

• Talcott KE, Ratnam K, Sundquist SM, Lucero AS, Lujan BJ, Tao W, Porco TC, Roorda A, Duncan JL. Longitudinal study of cone photoreceptors during retinal degeneration and in response to ciliary neurotrophic factor treatment. Invest Ophthalmol Vis Sci. 2011 Apr 6;52(5):2219-26. doi: 10.1167/iovs.10-6479.

  PMID: 21087953 BACKGROUND

MeSH Terms

Conditions

Retinitis Pigmentosa; Usher Syndromes

Interventions

Ciliary Neurotrophic Factor; Electroconvulsive Therapy; salicylhydroxamic acid

Condition Hierarchy (Ancestors)

Eye Diseases, Hereditary; Eye Diseases; Retinal Dystrophies; Retinal Degeneration; Retinal Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Deaf-Blind Disorders; Deafness; Hearing Loss; Hearing Disorders; Ear Diseases; Otorhinolaryngologic Diseases; Hearing Loss, Sensorineural; Sensation Disorders; Neurologic Manifestations; Nervous System Diseases; Blindness; Vision Disorders; Abnormalities, Multiple; Congenital Abnormalities; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Nerve Growth Factors; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Nerve Tissue Proteins; Biological Factors; Convulsive Therapy; Psychiatric Somatic Therapies; Behavioral Disciplines and Activities; Electroshock; Psychological Techniques

Results Point of Contact

• Title: Neurotech, Sr. Director of Clinical Operations
• Organization: Neurotech USA, Inc.

p.davis@neurotechusa.com

629-333-5804

Study Officials

• Jacque Duncan, MD

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Participants are considered in screening upon signing of the consent. Enrollment does not occur until participant is deemed eligible, as per screening, and randomized for implant. As such, there were 22 total participants enrolled in the study. There was a participant who died prior to screening procedures being conducted of which was captured in the AE section as the death occurred after consent to enter screening period. However, this participant was not enrolled as they had not completed screening or randomization for implant.

Study Record Dates

• First Submitted: January 19, 2012
• First Posted: February 10, 2012
• Study Start: January 1, 2012
• Primary Completion: July 1, 2019
• Study Completion: July 1, 2019
• Last Updated: February 14, 2023
• Results First Posted: February 14, 2023

Record last verified: 2023-02

Locations

US (1)