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

Primary Purpose

Retinitis Pigmentosa, Usher Syndrome Type 2, Usher Syndrome Type 3

Status

Completed

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

NT-501

Sham

About this trial

This is an interventional treatment trial for Retinitis Pigmentosa focused on measuring Retinitis pigmentosa, Usher syndrome type 2, Usher syndrome type 3, Cone photoreceptor, Vision, Blind

Eligibility Criteria

18 Years - 55 Years (Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

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.

Exclusion Criteria:

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.
Participant has a history of myocardial infarction within the last 12 months.
Participant is pregnant or lactating.
Participant is considered immunodeficient or has a known history of HIV. A laboratory test for HIV will be performed, and a positive result is also an exclusion criterion.
Participant with a history of ocular herpes zoster.
Participant is on chemotherapy.
Participant has a history of malignancy, except study participant with cancer treated successfully ≥5 years prior to inclusion in the trial.
Participant with severe hearing disabilities in both ears.
Participant who has been diagnosed and treated for amblyopia as an infant.
Participant who, in the opinion of the study doctor, will not be a good study subject.

Sites / Locations

University of California, San Francisco

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Sham Comparator

Arm Label

NT-501

Sham

Arm Description

Encapsulated cell therapy that delivers ciliary neurotrophic factor to the retina

Sham surgery

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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

Difference in change in logMAR visual acuity between NT-501 and contralateral sham-treated eyes. Change in visual acuity was measured based on the number of letters read on a vision chart using a standard protocol. The log of the mean angle of resolution (logMAR) was used to describe the size of the smallest letters that the patient could read. A logMAR value of 0.00 corresponds to visual acuity of 20/20, a logMAR value of 0.3 corresponds to visual acuity of 20/40, a logMAR value of 0.7 corresponds to visual acuity of 20/100, and a logMAR value of 1.00 corresponds to visual acuity of 20/200.

Full Information

NCT ID

NCT01530659

First Posted

January 19, 2012

Last Updated

February 9, 2023

Sponsor

Neurotech Pharmaceuticals

Collaborators

University of California, San Francisco

1. Study Identification

Unique Protocol Identification Number

NCT01530659

Brief Title

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

Official Title

Photoreceptor Structure in A Phase 2 Study of Encapsulated Human NTC-201 Cell Implants Releasing Ciliary Neurotrophic Factor (CNTF) for Participants With Retinitis Pigmentosa Using Rates of Change in Cone Spacing and Density

Study Type

Interventional

2. Study Status

Record Verification Date

February 2023

Overall Recruitment Status

Completed

Study Start Date

January 2012 (undefined)

Primary Completion Date

July 1, 2019 (Actual)

Study Completion Date

July 1, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Neurotech Pharmaceuticals

Collaborators

University of California, San Francisco

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

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.

Detailed Description

This clinical trial is a prospective, randomized, double-masked, sham-controlled trial of 30 study participants who have early-stage retinitis pigmentosa, or Usher syndrome (type 2 or 3). The trial will be conducted at the University of California, San Francisco. Individuals with these diseases experience gradually worsening vision that ultimately may lead to blindness due to a genetic condition in which specialized cells in the eye's retina called photoreceptor cells cease functioning and/or die. The study is intended to use a relatively new, non-invasive technology called AOSLO (adaptive optics scanning laser ophthalmoscopy) in combination with a routine standard of care measurement called sdOCT (Spectral Domain Optical Coherence Tomography) to demonstrate that when a device that secretes an investigational drug called CNTF (Ciliary Neurotrophic Factor) is surgically placed in the patient's eye, one type of photoreceptor called "cone photoreceptors" is preserved such that the gradual loss of vision is halted.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

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

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Model Description

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.

Masking

ParticipantInvestigator

Allocation

Randomized

Enrollment

22 (Actual)

8. Arms, Groups, and Interventions

Arm Title

NT-501

Arm Type

Experimental

Arm Description

Encapsulated cell therapy that delivers ciliary neurotrophic factor to the retina

Arm Title

Sham

Arm Type

Sham Comparator

Arm Description

Sham surgery

Intervention Type

Drug

Intervention Name(s)

NT-501

Other Intervention Name(s)

CNTF, Encapsulated Cell Therapy, ECT

Intervention Description

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

Intervention Type

Procedure

Intervention Name(s)

Sham

Intervention Description

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

Primary Outcome Measure Information:

Title

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

Description

Time Frame

Post-op Month 36

Secondary Outcome Measure Information:

Title

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

Description

Time Frame

Post-op Month 36

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

55 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: 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. Exclusion Criteria: 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. Participant has a history of myocardial infarction within the last 12 months. Participant is pregnant or lactating. Participant is considered immunodeficient or has a known history of HIV. A laboratory test for HIV will be performed, and a positive result is also an exclusion criterion. Participant with a history of ocular herpes zoster. Participant is on chemotherapy. Participant has a history of malignancy, except study participant with cancer treated successfully ≥5 years prior to inclusion in the trial. Participant with severe hearing disabilities in both ears. Participant who has been diagnosed and treated for amblyopia as an infant. Participant who, in the opinion of the study doctor, will not be a good study subject.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Jacque Duncan, MD

Organizational Affiliation

University of California, San Francisco

Official's Role

Principal Investigator

Facility Information:

Facility Name

University of California, San Francisco

City

San Francisco

State/Province

California

ZIP/Postal Code

94143

Country

United States

12. IPD Sharing Statement

Citations:

PubMed Identifier

17591900

Citation

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.

Results Reference

background

PubMed Identifier

16505355

Citation

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.

Results Reference

background

PubMed Identifier

21087953

Citation

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.

Results Reference

background

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

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