Retinitis PigmentosaPhase 2NCT00447993
A Study of Encapsulated Cell Technology (ECT) Implant for Patients With Late Stage Retinitis Pigmentosa
A Phase 2 study testing Low Dose NT-501 and High Dose NT-501 in people with Retinitis Pigmentosa, run by Neurotech Pharmaceuticals at 11 sites in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 to 68 years
- Conditions the study is for
- Retinitis Pigmentosa
- What is being tested?
- Low Dose NT-501 and High Dose NT-501
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 67 participants
- Where
- 11 sitesUnited States
- Study dates
- 8 Jan 2007to 26 May 2009
- 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 68 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Participant was older than 18, but less than 68 years of age.
- 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.
- 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.
- Participant was medically able to undergo ophthalmic surgery for the NT-501 device.
- Participant's clinical diagnosis was consistent with retinal degeneration in the set of retinitis pigmentosa (RP) dystrophies characterized by the following features:
- clinical evidence of progressive photoreceptor cell dysfunction and degeneration of the outer retina.
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- intraretinal bone-spicule'-like pigment observed in clinical examination (not necessarily applicable to choroideremia).
- peripheral visual field constriction documented on standard testing.
- symptomatic night blindness.
- 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.
- Each eye had a visual acuity score of at least 24 (20/320) and no more than 63 (20/63) letters.
- Each eye had an ERG amplitude reduced below the 95% limit of normal (CI) per site by Full Field 28-32 Hz flicker.
Who cannot join
- Participant was medically unable to comply with study procedures or follow-up visits.
- Participant had glaucoma (defined as independent optic atrophy causing vision loss), irrespective of whether it was currently treated or untreated.
- Participant had classic syndromic RP.
- 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.
- 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.
- 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.
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- 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.
- Participant had evidence of corneal opacification or lack of optical clarity.
- 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.
- Participant was receiving systemic steroids or other immunosuppressive medications.
- Participant had undergone LASIK surgery or other refractive surgery for either eye in less than 6 months prior to screening.
- 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.
- Participant had previous exposure to an intra-ocular device or implant into the eye (excluding intra-ocular lens).
- Participant had uveitis or other retinal inflammatory disease.
- Participant was receiving oral or other insulin treatment for diabetes.
- Participant who had a history of myocardial infarction within the last 12 months.
- Participant was pregnant or lactating.
- 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.
- Participant with a history of ocular herpes zoster.
- Participant was on chemotherapy.
- Participant had a history of malignancy, except study participants having cancer treated successfully ≥5 years prior to inclusion in the trial.
- Participant with severe hearing disabilities in both ears.
- Participant with diabetic retinopathy in either eye.
- Participant had history of retinal detachment in either eye.
- Participant had been diagnosed and treated for amblyopia as an infant.
- Participant with a history of Pars Plana Vitrectomy.
Trial locations and contacts
11 sites in 1 country.
11 sites in 1 country
United States11 sites
Kellogg Eye Center
Ann Arbor, Michigan, 48105
Retina-Vitreous Associates Medical Group
Beverly Hills, California, 90211
Retina Foundation of Southwest
Dallas, Texas, 75231
Retina Group of Florida
Hollywood, Florida, 33021-6746
University of Florida
Jacksonville, Florida, 32216-1480
The Hamilton Eye Institute
Memphis, Tennessee, 38163
University of Minnesota
Minneapolis, Minnesota, 55455-0501
NY University Medical Center
New York, New York, 10016
Casey Eye Institue
Portland, Oregon, 97239-4197
University of Califoria, Davis
Sacramento, California, 95817
University of California, San Francisco
San Francisco, California, 94143-0730
About this study
Official title: 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.
Read the detailed description
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.
- Conditions
- Retinitis Pigmentosa
- Being tested
- Low Dose NT-501, High Dose NT-501
- Keywords
- Retinitis Pigmentosa, eye disease, retinal disorder, CNTF
- Medical subject headings
- Retinitis Pigmentosa, Eye Diseases, Retinal Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Low Dose NT-501Combination product
Also called CNTF implant
Low Dose NT-501 Implanted in study eye and fellow eye received sham surgery
High Dose NT-501Combination product
Also called CNTF implant
High Dose NT-501 Implanted in study eye and fellow eye received sham surgery
| Study group | Role | What they receive |
|---|---|---|
| Low Dose NT-501 | Experimental | NT-501 Low Dose Implant: encapsulated cell therapy that delivers ciliary neurotrophic factor to the retina
Sham Implant in Fellow Eye Receives: Combination Product: Low Dose NT-501 |
| High Dose NT-501 | Experimental | NT-501 High Dose Implant: encapsulated cell therapy that delivers ciliary neurotrophic factor to the retina
Sham Implant in Fellow Eye Receives: Combination Product: High Dose NT-501 |
What is being measured
The primary outcome is the main question the study is designed to answer.
The Primary Outcome is the Change in Best-corrected Visual Acuity (BCVA) Using the Electronic Visual Acuity (EVA) Technology at Month 12.
The primary efficacy endpoint was the proportion of patients demonstrating an improvement in best-corrected visual acuity (BCVA), defined as an increase of 10 letters or more at the 1-Year post-implant visit (pre-explant, if explant is completed). No response is defined as an improvement of <10 letters.
Measured: 12 months post-implant
Secondary outcomes (1)
Number of Participants With and Without Best Corrected Visual Acuity Response Over the 18-month Follow-up Period (Months 1, 3, 6, 12 and 18)
The key visits for efficacy assessments were Months 1, 3, 6, 12 and 18. At these time points, BCVA was measured 3 times and the mean outcome reported. The assessments were conducted by masked technicians. The change from baseline for BCVA was summarized by time. Response is defined as an improvement in visual acuity by an increase of 10 letters or more whereas no response is <10 letters.
Measured: From initial implant to 18 months post-implant
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Mar 2007 (estimated)
- Study start8 Jan 2007
- Primary completion26 May 2009
- Study completion26 May 2009
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 (2)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
- Masking
- Double blind
- Who is masked
- Participant, Outcomes assessor
- Enrolment
- 67 participants (actual)
Sponsor and investigators
- Lead sponsor
- Neurotech Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- David Birch, MD, Principal investigator, Retina Foundation of the Southwest
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00447993
- Sponsor's protocol ID
- CNTF 3
- Status last verified
- Jul 2024
- First submitted
- 9 Mar 2007
- Last updated
- 13 Aug 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- Yes
- Individual data sharing
- No
Publications
Birch DG, Weleber RG, Duncan JL, Jaffe GJ, Tao W; Ciliary Neurotrophic Factor Retinitis Pigmentosa Study Groups. Randomized trial of ciliary neurotrophic factor delivered by encapsulated cell intraocular implants for retinitis pigmentosa. Am J Ophthalmol. 2013 Aug;156(2):283-292.e1. doi: 10.1016/j.ajo.2013.03.021. Epub 2013 May 10.
PubMed 23668681Kauper K, McGovern C, Sherman S, Heatherton P, Rapoza R, Stabila P, Dean B, Lee A, Borges S, Bouchard B, Tao W. Two-year intraocular delivery of ciliary neurotrophic factor by encapsulated cell technology implants in patients with chronic retinal degenerative diseases. Invest Ophthalmol Vis Sci. 2012 Nov 1;53(12):7484-91. doi: 10.1167/iovs.12-9970.
PubMed 23049090
Study at a glance
From the registry record, last updated by the sponsor on 13 Aug 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT00447993
- Acronym / sponsor ID
- CNTF 3
- Conditions
- Retinitis Pigmentosa
- Keywords
- Retinitis Pigmentosa, eye disease, retinal disorder, CNTF
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 67 participants (actual)
- Lead sponsor
- Neurotech PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- 8 Jan 2007 (actual)
- Primary completion
- 26 May 2009 (actual)
- Study completion
- 26 May 2009 (actual)
- First posted
- 15 Mar 2007 (estimated)
- Results
- Posted 13 Aug 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Low Dose NT-501 | Experimental | Combination Product: Low Dose NT-501NT-501 Low Dose Implant: encapsulated cell therapy that delivers ciliary neurotrophic factor to the retina Sham Implant in Fellow Eye |
| High Dose NT-501 | Experimental | Combination Product: High Dose NT-501NT-501 High Dose Implant: encapsulated cell therapy that delivers ciliary neurotrophic factor to the retina Sham Implant in Fellow Eye |
Who may qualify
- Ages
- 18 to 68 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- Participant was older than 18, but less than 68 years of age.
- 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.
- 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.
- Participant was medically able to undergo ophthalmic surgery for the NT-501 device.
- Participant's clinical diagnosis was consistent with retinal degeneration in the set of retinitis pigmentosa (RP) dystrophies characterized by the following features:
Key exclusion criteria (27 listed)
- Participant was medically unable to comply with study procedures or follow-up visits.
- Participant had glaucoma (defined as independent optic atrophy causing vision loss), irrespective of whether it was currently treated or untreated.
- Participant had classic syndromic RP.
- 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.
- 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.
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 |
|---|---|---|
| Low Dose NT-501Also: CNTF implantLow Dose NT-501 Implanted in study eye and fellow eye received sham surgery | Combination product | Low Dose NT-501 |
| High Dose NT-501Also: CNTF implantHigh Dose NT-501 Implanted in study eye and fellow eye received sham surgery | Combination product | High Dose NT-501 |
Primary outcome
The Primary Outcome is the Change in Best-corrected Visual Acuity (BCVA) Using the Electronic Visual Acuity (EVA) Technology at Month 12.
Time frame: 12 months post-implant
The primary efficacy endpoint was the proportion of patients demonstrating an improvement in best-corrected visual acuity (BCVA), defined as an increase of 10 letters or more at the 1-Year post-implant visit (pre-explant, if explant is completed). No response is defined as an improvement of <10 letters.
1 secondary outcome
Number of Participants With and Without Best Corrected Visual Acuity Response Over the 18-month Follow-up Period (Months 1, 3, 6, 12 and 18)
Time frame: From initial implant to 18 months post-implant
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Aug 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 23668681Birch DG, Weleber RG, Duncan JL, Jaffe GJ, Tao W; Ciliary Neurotrophic Factor Retinitis Pigmentosa Study Groups. Randomized trial of ciliary neurotrophic factor delivered by encapsulated cell intraocular implants for retinitis pigmentosa. Am J Ophthalmol. 2013 Aug;156(2):283-292.e1. doi: 10.1016/j.ajo.2013.03.021. Epub 2013 May 10.
- Derived from this study: PubMed 23049090Kauper K, McGovern C, Sherman S, Heatherton P, Rapoza R, Stabila P, Dean B, Lee A, Borges S, Bouchard B, Tao W. Two-year intraocular delivery of ciliary neurotrophic factor by encapsulated cell technology implants in patients with chronic retinal degenerative diseases. Invest Ophthalmol Vis Sci. 2012 Nov 1;53(12):7484-91. doi: 10.1167/iovs.12-9970.
- Individual participant dataSharing planned: No
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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.
David Birch, MD principal investigator
Retina Foundation of the Southwest
11 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Low Dose NT-501 and High Dose NT-501 in people with Retinitis Pigmentosa, run by Neurotech Pharmaceuticals at 11 sites 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 12 inclusion and 27 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 13 Aug 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 11 sites 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. 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 13 Aug 2024). 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?
The Primary Outcome is the Change in Best-corrected Visual Acuity (BCVA) Using the Electronic Visual Acuity (EVA) Technology at Month 12. (time frame: 12 months post-implant). 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 NCT00447993, which also lists 2 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 13 Aug 2024.