Retinitis PigmentosaPhase 2NCT01530659
Retinal Imaging in CNTF -Releasing Encapsulated Cell Implant Treated Patients for Early-stage Retinitis Pigmentosa
A Phase 2 study testing NT-501 in people with Retinitis Pigmentosa and Usher Syndrome Type 2, run by Neurotech Pharmaceuticals at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 55 years
- Conditions the study is for
- Retinitis Pigmentosa, Usher Syndrome Type 2, Usher Syndrome Type 3
- What is being tested?
- NT-501
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 22 participants
- Where
- 1 siteUnited States
- Study dates
- Jan 2012to 1 Jul 2019
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 55 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- 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.
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- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
University of California, San Francisco
San Francisco, California, 94143
About this study
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
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.
Read the 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.
- Being tested
- NT-501, Sham
- Keywords
- Retinitis pigmentosa, Usher syndrome type 2, Usher syndrome type 3, Cone photoreceptor, Vision, Blind
- Medical subject headings
- Retinitis Pigmentosa, Usher Syndromes
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NT-501Drug
Also called CNTF, Encapsulated Cell Therapy, ECT
Study participants will undergo surgery to have an NT-501 Encapsulated Cell Therapy implant placed into the study eye.
ShamProcedure or surgery
Non-penetrating sham procedure to mimic implant procedure in the other eye.
| Study group | Role | What they receive |
|---|---|---|
| NT-501 | Experimental | Encapsulated cell therapy that delivers ciliary neurotrophic factor to the retina Receives: Drug: NT-501 |
| Sham | Sham comparator | Sham surgery Receives: Procedure: Sham |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Post-op Month 36
Secondary outcomes (1)
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.
Measured: Post-op Month 36
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Feb 2012 (estimated)
- Study startJan 2012
- Primary completion1 Jul 2019
- Study completion1 Jul 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Retinitis PigmentosaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- 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
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 22 participants (actual)
Sponsor and investigators
- Lead sponsor
- Neurotech Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- University of California, San Francisco
- Responsible party
- Sponsor
- Investigators
- Jacque Duncan, MD, Principal investigator, University of California, San Francisco
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01530659
- Sponsor's protocol ID
- AOSLO-CNTF-FFB-01
- Other IDs
- FD-R-004100-01A1
- Status last verified
- Feb 2023
- First submitted
- 19 Jan 2012
- Last updated
- 14 Feb 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
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.
PubMed 17591900Sieving 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.
PubMed 16505355Talcott 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.
PubMed 21087953
Study at a glance
From the registry record, last updated by the sponsor on 14 Feb 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01530659
- Acronym / sponsor ID
- AOSLO-CNTF-FFB-01
- Keywords
- Retinitis pigmentosa, Usher syndrome type 2, Usher syndrome type 3, Cone photoreceptor, Vision, Blind
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 22 participants (actual)
- Lead sponsor
- Neurotech PharmaceuticalsIndustry (pharma, biotech, devices)
- Collaborators
- University of California, San Francisco
- Study start
- Jan 2012
- Primary completion
- 1 Jul 2019 (actual)
- Study completion
- 1 Jul 2019 (actual)
- First posted
- 10 Feb 2012 (estimated)
- Results
- Posted 14 Feb 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
- 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.
| Arm | Type | Receives |
|---|---|---|
| NT-501 | Experimental | Drug: NT-501Encapsulated cell therapy that delivers ciliary neurotrophic factor to the retina |
| Sham | Sham comparator | Procedure: ShamSham surgery |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (11 listed)
- 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.
Key exclusion criteria (24 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| NT-501Also: CNTF, Encapsulated Cell Therapy, ECTStudy participants will undergo surgery to have an NT-501 Encapsulated Cell Therapy implant placed into the study eye. | Drug | NT-501 |
| ShamNon-penetrating sham procedure to mimic implant procedure in the other eye. | Procedure or surgery | Sham |
Primary outcome
Mean Change in Cone Spacing in Arcminutes (Z Score) of 2 Baseline Values Were Compared With Measurements Obtained at Post-op Month 36
Time frame: 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.
1 secondary outcome
Difference in logMAR Visual Acuity Change Between CNTF- and Sham Treated Eyes
Time frame: Post-op Month 36
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Feb 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 17591900Duncan 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.
- Background: PubMed 16505355Sieving 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.
- Background: PubMed 21087953Talcott 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jacque Duncan, MD principal investigator
University of California, San Francisco
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing NT-501 in people with Retinitis Pigmentosa and Usher Syndrome Type 2, run by Neurotech Pharmaceuticals at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 24 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 14 Feb 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 14 Feb 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Mean Change in Cone Spacing in Arcminutes (Z Score) of 2 Baseline Values Were Compared With Measurements Obtained at Post-op Month 36 (time frame: Post-op Month 36). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01530659, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Feb 2023.