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| Name | Class |
|---|---|
| California Institute for Regenerative Medicine (CIRM) | OTHER |
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The investigator is examining the safety of transplanting cells into the subretinal space of patients with Retinitis Pigmentosa (RP). The cells are called neural progenitor cells, which are a type of stem cell that can become several different types of cells in the nervous system. These cells have been derived to specifically become astrocytes, which is a type of neuronal cell. The cells are called "CNS10-NPC." The investigational treatment has been tested in animals, but it has not yet been tested in people. In this study, the investigators want to learn if CNS10-NPC cells are safe to transplant into the subretinal space of people.
This study will be the first to use a human progenitor cell line to treat retinitis pigmentosa in people. This is a Phase 1/2a, single-center, open label, safety study of two escalating doses of human neural progenitor cells (CNS10-NPC) delivered unilaterally to the subretinal space of subjects with RP.
Subjects meeting all Eligibility Criteria and providing Informed Consent will be enrolled in one of two sequential dosing groups. Subjects will be treated sequentially with a minimum of one month interval between surgeries for the first three subjects in each dosing cohort. The remaining subjects in the cohort will be treated with a minimum interval of at least one week between surgeries.
Primary objective. To assess the safety and tolerability of two escalating doses of clinical grade human fetal cortical-derived neural progenitor cells (CNS10-NPC) administered in the subretinal space of one eye (unilaterally) in patients with retinitis pigmentosa (RP).
Secondary objectives. Within constraints of a small first in-human study focused on safety:
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Group 1A | Experimental | Visual acuity of 20/200 or worse Single, unilateral, subretinal injection of 300,000 CNS10-NPC (n=3) |
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| Group 1B | Experimental | Visual acuity of 20/200 or worse Single, unilateral, subretinal injection of 1,000,000 CNS10-NPC (n=3) |
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| Group 2 | Experimental | Visual acuity between 20/80 and 20/200 Single, unilateral, subretinal injection of 1,000,000 CNS10-NPC (n=10) |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| CNS10-NPC implantation | Biological | All patients will receive a single, unilateral, subretinal injection of CNS10-NPC |
|
| Measure | Description | Time Frame |
|---|---|---|
| Safety as evaluated by incidence of Adverse Events (AE) and Serious Adverse Events (SAE) and their relationship to the intervention | Subjects will be followed postoperatively for 12 months | |
| Safety, as evaluated by changes in the complete blood count | Subjects will be followed postoperatively for 12 months | |
| Safety, as evaluated by changes in the comprehensive metabolic panel | Subjects will be followed postoperatively for 12 months | |
| Safety, as evaluated by changes in Donor Specific Antibodies | Subjects will be followed postoperatively for 12 months | |
| Safety, as evaluated by changes in the urinalysis | Subjects will be followed postoperatively for 12 months | |
| Safety, as evaluated by changes in Visual Acuity | ETRDS, or FrACT in cases of very low vision. | Subjects will be followed postoperatively for 12 months |
| Safety, as evaluated by changes in visual field | Goldman perimetry will be used for central visual fields and microperimetry will be used for peripheral visual fields | Subjects will be followed postoperatively for 12 months |
| Safety, as evaluated by changes in Spectral Domain Optical Coherence Tomography (SD-OCT) | Ellipsoid zone measurement through SD-OCT will be performed |
| Measure | Description | Time Frame |
|---|---|---|
| Slit lamp examination | Performed 7 times over 15 months | |
| Intraocular pressure measurement | Performed 7 times over 15 months | |
| Funduscopic examination |
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Inclusion Criteria:
To participate in this study, the subject must be 18 years of age or older and must understand and sign the protocol's informed consent.
Participant with diagnosis of retinitis pigmentosa.
Clinical signs of retinitis pigmentosa.
A history of nyctalopia
Retinal pigmentary changes
Arteriolar attenuation
Waxy disc pallor
Electrophysiologic evidence of rod dysfunction on full field electroretinography
Visual field constriction.
3a. Participants in Group 1 (n=6) will have visual acuity equal to or worse than 20/200. Participants in Group 2 (n=10) will have visual acuity equal to or worse than 20/80.
3b. Group 1 participants will have central visual field of 40 degrees diameter or less. Group 2, participants will have a measurable visual field defect.
4. Participant will be medically able to undergo ophthalmic surgery.
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| David Liao, MD, PhD | Retina-Vitreous Associates Medical Group | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Retina-Vitreous Associates Medical Group | Beverly Hills | California | 90211 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 37743503 | Derived | Lu B, Avalos P, Svendsen S, Zhang C, Nocito L, Jones MK, Pieplow C, Saylor J, Ghiam S, Block A, Fernandez M, Ljubimov AV, Small K, Liao D, Svendsen CN, Wang S. GMP-grade human neural progenitors delivered subretinally protect vision in rat model of retinal degeneration and survive in minipigs. J Transl Med. 2023 Sep 25;21(1):650. doi: 10.1186/s12967-023-04501-z. |
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| ID | Term |
|---|---|
| D012174 | Retinitis Pigmentosa |
| D012164 | Retinal Diseases |
| D012162 | Retinal Degeneration |
| ID | Term |
|---|---|
| D015785 | Eye Diseases, Hereditary |
| D005128 | Eye Diseases |
| D058499 | Retinal Dystrophies |
| D030342 | Genetic Diseases, Inborn |
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| Subjects will be followed postoperatively for 12 months |
| Performed 7 times over 15 months |
| Fundus photography (color, red free, or infrared) | Performed 4 times over 15 months |
| Fundus Autofluorescence (FAF) | Performed 4 times over 15 months |
| Best Corrected Visual Acuity | Performed 7 times over 15 months |
| Visual Function Questionnaire-25 (VFQ-25) | The Visual Function Questionnaire-25 is graded in a scale from 0-100 where a higher number represents better function | Performed 5 times over 15 months |
| Spectral domain optical coherence tomography (SD-OCT) | Retinal Thickness | Performed 5 times over 15 months |
| Electroretinography (ERG) | Performed 5 times over 15 months |
| Goldmann visual field area (microperimetry) | Performed 5 times over 15 months |
| Change in rate of vision field loss | Through study completion, ~15 months. |
| D009358 |
| Congenital, Hereditary, and Neonatal Diseases and Abnormalities |