Clinical Study to Assess Safety and Efficacy of Subretinal Injection of Human Neural Progenitor Cells for Treatment of Retinitis Pigmentosa

Cedars-Sinai Medical Center1 site in 1 country16 target enrollmentJuly 22, 2021

ConditionsRetinitis Pigmentosa

InterventionsCNS10-NPC implantation

DrugsCNS10-NPC implantation

Overview

Phase: Phase 1
Intervention: CNS10-NPC implantation
Conditions: Retinitis Pigmentosa
Sponsor: Cedars-Sinai Medical Center
Enrollment: 16
Locations: 1
Primary Endpoint: Safety, as evaluated by changes in the complete blood count
Status: Active, not recruiting
Last Updated: 8 months ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

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.

Detailed Description

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: 1. Determine if CNS10-NPC can engraft and survive long-term in the retina of transiently immunosuppressed subjects, 2. Obtain evidence that subretinal injection of CNS10-NPC can favorably impact the progression of vision loss in subjects with moderate RP.

Registry

clinicaltrials.gov

Start Date

July 22, 2021

End Date

July 1, 2026

Last Updated

8 months ago

Study Type

Interventional

Study Design

Sequential

Sex

All

Investigators

Sponsor

Cedars-Sinai Medical Center

Responsible Party

Principal Investigator

Clive Svendsen

Director, Regenerative Medicine Institute

Cedars-Sinai Medical Center

Eligibility Criteria

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/

Exclusion Criteria

•Presence of significant ocular abnormalities that would preclude the planned surgery or interfere with the interpretation of study endpoints (e.g. glaucoma, corneal or significant lens opacities, pre-existing uveitis, intraocular infection, macular edema, choroidal neovascularization). Any ocular diseases that the investigator feels would interfere with accurate ocular measurements. This would exclude potential subjects with significant cataract, corneal scars or significant corneal irregularities such as keratoconus, previous penetrating keratoplasty or glaucoma with central visual field.
•Any pre-existing factor or history of eye disease that may predispose to an increased risk of surgical complications in the study eye (e.g. trauma, previous surgery other than uncomplicated cataract surgery, uveitis, congenital developmental or structural abnormalities).
•Concomitant systemic diseases including those in which the disease itself, or the treatment for the disease, can alter ocular function or immune status (e.g. malignancies, uncontrolled diabetes).
•Any ocular surgery or laser in either eye within 12 weeks of screening.
•Any contraindication to pupil dilatation in either eye.
•Treatment with intravitreal, subtenon or periocular steroid within 4 months of enrollment.
•Any known allergy to any component of the delivery vehicle or diagnostic agents used during the study (e.g., dilation drops), or medications planned for use during the peri-operative period including corticosteroids, tacrolimus and mycophenolate.
•Imminently life-threatening illness.
•Abuse of alcohol or any illegal substance(s) within 12 months of the procedure.
•Laboratory test abnormalities or abnormalities in electrocardiogram or chest X-ray, which in the opinion of the Principal Investigator are clinically significant and would make the patient unable to tolerate study procedures.

Arms & Interventions

Group 1A

Visual acuity of 20/200 or worse Single, unilateral, subretinal injection of 300,000 CNS10-NPC (n=3)

Intervention: CNS10-NPC implantation

Group 1B

Visual acuity of 20/200 or worse Single, unilateral, subretinal injection of 1,000,000 CNS10-NPC (n=3)

Intervention: CNS10-NPC implantation

Group 2

Visual acuity between 20/80 and 20/200 Single, unilateral, subretinal injection of 1,000,000 CNS10-NPC (n=10)

Intervention: CNS10-NPC implantation