Blind World


A Phase I Study of NT-501, an Implant of Encapsulated Human NTG-210 Cells Releasing Ciliary Neurtrophic Factor (CNTF), in Patients with Retinitis Pigmentosa.





Editor's Note:
A related story, from the Foundation Fighting Blindness (FFB), is appended to the end of this article.



June 23, 2003.

[No authors listed.]
U.S. National Library of Medicine,
Contact NLM Customer Service.
National Institutes of Health,
Department of Health & Human Services.




A Phase I Study of NT-501, an Implant of Encapsulated Human NTG-210 Cells Releasing Ciliary Neurtrophic Factor (CNTF), in Patients with Retinitis Pigmentosa.


This study is currently recruiting patients.


Sponsored by


National Eye Institute (NEI)


Purpose


Retinitis Pigmentaos (RP) is a group of incurable degenerative diseases of the retina that have a complex molecular etiology. Approximately 100,000 Americans suffer from inherited retinal degenerative RP. More than 100 RP-inducing mutations have been identified in several genes including: rhodopsin, the rod visual pigment; peripherin, a membrane structure protein; and PDEB, the beta subunit of rod cyclic GMP (cGMP) phosphodiesterase. However, the genotype is unknown for the majority of patients. Despite this genetic heterogeneity, there tends to be a common pattern of visual loss in patients with RP. Typically, patients experience disturbance in night vision early in life due to the degeneration of rod photoreceptors. The remaining cone photoreceptors become their mainstay of vision, but over the years and decades, the cones slowly degenerate, leading to blindness. These two phases of degeneration in the visual life of an RP patient may involve different underlying pathogenic mechanisms. Regardless of the initial causative defects, the end results are photoreceptor degeneration. This common pathogenesis pathway provides a target for therapeutic intervention.


To date, there are few available, effective treatments for retinal degenerative disorders. One major challenge is to deliver potential therapeutic agents to the back of the eye, in particular to the retina. The blood-eye barrier prevents the penetration of a variety of molecules to the neurosensory retina in a similar manner to the action of the blood-brain barrier, which exists between the central nervous system and systemic circulation. To overcome this challenge, Neurotech USA, Inc. (Neurotech) developed encapsulated cell technology (ECT), specifically an NT-501 device, to enable controlled, sustained delivery of therapeutic agents directly into the intra-ocular fluids and thus providing direct access to the retina. ECT utilizes cells encapsulated within a semi-permeable polymer device that secretes therapeutic factors directly into the vitreous. In addition, ECT devices can be retrieved, providing an added level of safety.


Histopathologic studies have demonstrated the possibility of growth factors, neurotrophic factors, and cytokines as therapeutics for RP. Specifically, ciliary neurotrophic factor (CNTF) has proven to be the most effective in reducing retinal degeneration. Therefore, the use of an implanted NT-501 device, which secretes CNTF into the retina, may be beneficial in patients with RP and other retinal degenerative diseases.


This pilot study will assess the ophthalmic and systemic safety, and to some extent efficacy, of a novel intra-ocular NT-501 implant in patients with RP and poor visual acuity in one eye. The main purpose of the study is to assess the safety of the NT-501 implant. Secondary outcomes will include the anterior chamber cell scale and vitreous haze grading to measure inflammation, which may be caused by the implant. Other secondary outcome measures related to potential product performance are visual acuity, visual fields, electroretinograms (ERG), and optical coherence tomography (OCT3) to determine retinal thickness.


Phase


Phase I


MEDLINEplus consumer health information


Study Type: Interventional


Study Design: Treatment, Safety


Further Study Details:


Retinitis Pigmentosa (RP) is a group of incurable degenerative diseases of the retina that have a complex molecular etiology. Approximately 100,000 Americans suffer from inherited retinal degenerative RP. More than 100 RP-inducing mutations have been identified in several genes including: rhodopsin, the rod visual pigment; peripherin, a membrane structure protein; and PDEB, the beta subunit of rod cyclic GMP (cGMP) phosphodiesterase. However, the genotype is unknown for the majority of patients. Despite this genetic heterogeneity, there tends to be a common pattern of visual loss in patients with RP. Typically, patients experience disturbance in night vision early in life due to the degeneration of rod photoreceptors. The remaining cone photoreceptors become their mainstay of vision, but over the years and decades, the cones slowly degenerate, leading to blindness. These two phases of degeneration in the visual life of an RP patient may involve different underlying pathogenic mechanisms. Regardless of the initial causative defects, the end results are photoreceptor degeneration. This common pathogenesis pathway provides a target for therapeutic intervention.


To date, there are few available, effective treatments for retinal degenerative disorders. One major challenge is to deliver potential therapeutic agents to the back of the eye, in particular to the retina. The blood-eye barrier prevents the penetration of a variety of molecules to the neurosensory retina in a similar manner to the action of the blood-brain barrier, which exists between the central nervous system and systemic circulation. To overcome this challenge, Neurotech USA, Inc. (Neurotech) developed encapsulated cell technology (ECT), specifically an NT-501 device, to enable controlled, sustained delivery of therapeutic agents directly into the intra-ocular fluids and thus providing direct access to the retina. ECT utilizes cells encapsulated within a semi-permeable polymer device that secretes therapeutic factors directly into the vitreous. In addition, ECT devices can be retrieved, providing an added level of safety.


Histopathologic studies have demonstrated the possibility of growth factors, neurotrophic factors, and cytokines as therapeutics for RP. Specifically, ciliary neurotrophic factor (CNTF) has proven to be the most effective in reducing retinal degeneration. Therefore, the use of an implanted NT-501 device, which secretes CNTF into the retina, may be beneficial in patients with RP and other retinal degenerative diseases.


This pilot study will assess the ophthalmic and systemic safety, and to some extent efficacy, of a novel intra-ocular NT-501 implant in patients with RP and poor visual acuity in one eye. The main purpose of the study is to assess the safety of the NT-501 implant. Secondary outcomes will include the anterior chamber cell scale and vitreous haze grading to measure inflammation, which may be caused by the implant. Other secondary outcome measures related to potential product performance are visual acuity, visual fields, electroretinograms (ERG), and optical coherence tomography (OCT3) to determine retinal thickness.


Eligibility


Genders Eligible for Study: Both


Criteria


INCLUSION CRITERIA:


1. To participate in this study, the participant must understand and sign the protocol's informed consent.


2.Paticipant diagnosis consistent with retinitis pigmentosa (RP) characterized by the following features:


a) progressive photoreceptor dysfunction an death


b) clinical degeneration of the outer retina


c) intraretinal 'bone-spicule' pigment


d) visual field constriction


e) night blindness


f) major reduction of both rod and cone electroretinogram (ERG) responses.


3. The first two participants have 20/400 vision or worse in the implant (study) eye with the same or better in the fellow eye, while the remainder of the participants will have visual acuity of 20/100 or worse.


4. Participant has an ERG less than 2 MV(28-32 Hz flicker)


5. Participant with central visual field of 40 degrees diameter or less with the Goldman V4e stimulus (independent of a peripheral crescent of any size)


6. Participant medically able to undergo ophthalmic surgery.


EXCLUSION CRITERIA:


1. Participant less than 18 years of age.


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


3. Participant has glaucoma.


4. Participant is receiving oral or other insulin treatment for diabetes.


5. Participant has cataract and it interferes with the assessment of the posterior segment inflammation using a standard slit lamp examination.


6. Participant has undergone intra-ocular lens replacement less than 6 months prior to enrollment.


7. Participant has participated in any other clinical trial of a drug or device within the last 6 months.


8. Participant is on chemotherapy.


9. Participant is on ocular medications known to be toxic to the lens, retina, or optic nerve.


10. Participant who is pregnant.


11. Participant with retinal inflammatory diseases.


12. Participant with macula edema


13. Participant with history of malignancy (except study participants having a basal cell carcinoma that was treated successfully, or other malignancy operated on and in remission of 5 years prior to inclusion in the trial).


14. Participant is considered immunodeficient or has a known history of HIV.


Expected Total Enrollment: 10


Location and Contact Information


Maryland


National Eye Institute (NEI),
9000 Rockville Pike,
Bethesda, Maryland, 20892,
United States.


Recruiting


Patient Recruitment and Public Liaison Office
1-800-411-1222.
prpl@mail.cc.nih.gov
TTY 1-866-411-1010.


More Information


Detailed Web Page


Publications


Aebischer P, Schluep M, Deglon N, Joseph JM, Hirt L, Heyd B, Goddard M, Hammang JP, Zurn AD, Kato AC, Regli F, Baetge EE. Intrathecal delivery of CNTF using encapsulated genetically modified xenogeneic cells in amyotrophic lateral sclerosis patients. Nat Med. 1996 Jun;2(6):696-9. Erratum in: Nat Med 1996 Sep;2(9):1041.


Aebischer P, Kato AC. Treatment of amyotrophic lateral sclerosis using a gene therapy approach. Eur Neurol. 1995;35(2):65-8. Review.


[No authors listed] A phase I study of recombinant human ciliary neurotrophic factor (rHCNTF) in patients with amyotrophic lateral sclerosis. The ALS CNTF Treatment Study (ACTS) Phase I-II Study Group. Clin Neuropharmacol. 1995 Dec;18(6):515-32.


Study ID Numbers 030234; 03-EI-0234


Study Start Date June 30, 2003


Record last reviewed June 23, 2003


Last Updated June 23, 2003


NLM Identifier NCT00063765


ClinicalTrials.gov processed this record on 2003-07-11


U.S. National Library of Medicine,
Contact NLM Customer Service
National Institutes of Health,
Department of Health & Human Services.






Related Story from the Foundation Fighting Blindness (FFB):



Encapsulated RPE Cells Reduce Photoreceptor Degeneration in Animal Models of Retinitis Pigmentosa.



Beneath the neural retina is a single layer of cells called the retinal pigment epithelium, or RPE, for short. The RPE supports the function of photoreceptor cells, providing nutrients and eliminating waste products. In early experiments, Foundation-supported researchers found that transplanted RPE cells markedly extend the life of photoreceptor cells in animal models of retinitis pigmentosa. Further research established that RPE cells produce a number of substances, called neurotrophic agents, that foster the health and survival of photoreceptor cells.


Neurotech has developed a novel drug delivery device containing genetically modified RPE cells. Encapsulated Cell Technology (ECT) consists of a small capsule that is implanted in the back of the eye, close to the retina. RPE cells within the capsule are genetically manipulated to produce large amounts of the neurotrophic agent called ciliary neurotrophic factor (CNTF). In previous experiments, injections of CNTF slowed vision loss in several animal models of RP. However, because of the chronic nature of these diseases, patients would require numerous eye injections of CNTF, raising serious safety concerns. The ECT device, with its modified RPE cells, overcomes this obstacle by providing a CNTF “drug factory” in the eye.


The ECT capsule contains very small pores that allow oxygen and nutrients to diffuse into the cells and also allow the survival factor to diffuse out. The tiny pores prevent the modified RPE cells from escaping and prevent the body’s immune system from reaching and attacking these foreign cells.


In recently published experiments, supported by The Foundation Fighting Blindness and Neurotech, the device dramatically halted vision loss in an RP animal model. With results from this and other safety studies, Neurotech plans to file an application with the Food and Drug Administration in early 2003 seeking approval to begin human clinical trials. If Neurotech gains approval from the FDA, details of a clinical trial will be forthcoming. The Foundation will keep you informed of developments as they occur.


Neurotech’s ECT device could pioneer drug treatment for the entire spectrum of retinal degenerative disease. Through strategic partnerships with industry, The Foundation is accelerating the pace of research.



©2003 Foundation Fighting Blindness.






Go to ...


Top of Page.

Previous Page.

List of Categories.

Home Page.





Blind World Website
Designed and Maintained by:
George Cassell
All Rights Reserved.



Copyright Notice
and Disclaimer.