Safety and Efficacy of Intravitreal Injection of Human Retinal Progenitor Cells in Adults With Retinitis Pigmentosa

A Prospective, Multicenter, Randomized, Study of the Safety and Efficacy of Intravitreal Injection of Human Retinal Progenitor Cells (jCell) in Adult Subjects With Retinitis Pigmentosa (RP)

This study evaluates the changes in visual function at 12 months following a single injection of human retinal progenitor cells compared to sham treated controls in a cohort of adult subjects with RP.

Study Overview

• Status: Completed
• Conditions: Retinitis Pigmentosa
• Intervention / Treatment: Biological: human retinal progenitor cells; Other: Mock injection

Detailed Description

There is no effective treatment for RP; once photoreceptors are lost, they do not regenerate. The rate of deterioration of vision varies from person to person, with most people with RP legally blind by age 40. Preclinical studies demonstrated that transplantation of retinal progenitor cells into the eye can result in both photoreceptor replacement and significant slowing of host photoreceptor loss. Thus, the primary goal of this therapy is to preserve, and potentially improve, vision by intervening in the disease at a time when dystrophic host photoreceptors can be protected and reactivated. Based on the demonstration of acceptable safety and tolerability in a phase 1/2a study, this phase 2b study is designed as a controlled comparison of the changes in visual function and functional vision in subjects who receive a single jCell injection in comparison to a comparable sham-treated control group of subjects with RP.

• Study Type: Interventional
• Enrollment (Actual): 84
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Irvine, California, United States, 92697
      • Gavin Herbert Eye Inst, Univ Cal Irvine
    • Los Angeles, California, United States, 90074
      • Retina-Vitreous Associates Medical Group
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Ophthalmic Consultants of Boston

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

Clinical diagnosis of RP confirmed by ERG and willing to consent to mutation typing, if not already done Best corrected visual acuity (BCVA) 20/80 or worse and no worse than 20/800 Adequate organ function and negative infectious disease screen Female of childbearing potential must have negative pregnancy test and be willing to use medically accepted methods of contraception throughout the study

Exclusion Criteria:

Eye disease other than RP that impairs visual function Pseudo-RP, cancer-associated retinopathies History of malignancy or other end-stage organ disease, or any chronic disease requiring continuous treatment with system steroids, anticoagulants or immunosuppressive agents Known allergy to penicillin or streptomycin Treatment with corticosteroids or any investigational or neuroprotectant therapy within 90 days of enrollment Cataract surgery within 3 months prior to enrollment

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Test (jCell injection) dose level 1; single intravitreal injection of 3.0 x 10e6 human retinal progenitor cells into the eye with the poorest visual acuity or, if vision is comparable in both eyes, the non-dominant eye	Biological: human retinal progenitor cells; live suspension of 3.0 or 6.0 x 10e6 human retinal progenitor cells (hRPC) suspended in clinical grade medium injected intravitreally under local anesthesia; Other Names: jCell
Other: Sham treated Control; a mock injection will be performed on the eye with the poorest vision in each Control subject (designated as the "study eye")	Other: Mock injection; pressing the hub of a syringe with no needle against the eye to mimic intravitreal injection
Experimental: test (jCell injection) dose level 2; single intravitreal injection of 6.0 x 10e6 human retinal progenitor cells into the eye with the poorest visual acuity or, if vision is comparable in both eyes, the non-dominant eye	Biological: human retinal progenitor cells; live suspension of 3.0 or 6.0 x 10e6 human retinal progenitor cells (hRPC) suspended in clinical grade medium injected intravitreally under local anesthesia; Other Names: jCell

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Best Corrected Visual Acuity (BCVA)	Mean change in BCVA in study eye from baseline to month 12 as assessed by E-ETDRS in ITT population. A letter score is used to compare change over time, with a higher number of letters representing better visual function, and a lower number of letters representing worse visual function. For example, 85 letters is equivalent to 20/20 visual acuity and 5 letters is equivalent to 20/800 visual acuity. A change value is derived for each subject by taking the letter score at 12 months and subtracting the letter score at baseline. A mean of all change values is then calculated for each arm.	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Contrast Sensitivity (CS) at 1.0 CPD	Assessment of the ability to detect changes in shades of grey, as measured with a vertical striped pattern that varies in width (cycles per degree or CPD); CS thresholds are created by taking the mean of multiple trials at each pattern width. A CS curve is created using a minimum of three pattern widths, one at the subject's peak or highest sensitivity, and then one larger and smaller pattern width on either side of the peak. For example, if a subject's CS peak appears to be at 2.0 CPD, then additional testing occurs at 1.0 and 4.0 CPD. RP patients have suppressed CS curves and the most common pattern widths are at 0.5, 1.0, 2.0, and 4.0 CPD. Severely impaired subjects (e.g., BCVA < 20/400) usually have flat curves with low values (e.g., 1.28), while in mildly impaired RP subjects the values can be higher (e.g., 7.12), but are rarely near normal. These data represent mean change in CS from baseline to 12 months, with greater values representing greater improvement in visual function.	12 months
Kinetic Visual Field (KVF)	Mean change in total area (degrees squared) of all islands of vision from baseline to 12 months.	12 months
Low Luminance Mobility Test (LLMT)	The LLMT identifies the performance of RP patients as they walk along an indoor pathway of arrows and obstacles at varying lighting levels. The Critical Illumination Level (CIL) is the light level below which the patient has a markedly slower pace and more errors than all light levels above (brighter than) that point. The LLMT uses light levels that go from very dim (0.12 lux) to a bright indoor room (500 lux), with evenly spaced increments that increase light by doubling the brightness of the room from the prior level. These evenly spaced light levels have been converted to a scale score to enable easier calculation of change scores. The dimmest light level of 0 lux (completely dark room) corresponds to a scale score of 13, whereas the brightest light level of 500 lux corresponds to a scale score of 0. A positive scale score change from baseline to 12 months represents improvement in low light vision, whereas a negative scale score change represents a decline in low light vision.	12 months
Low Vision Functional Questionnaire (Visual Ability)	The VA LV VFQ-48 (VFQ) is used to capture changes in patients' self-reporting of their difficulty with reading, mobility and performing other daily living activities affected by visual impairment. There are 4 scales on the VFQ including Visual Information, Reading, Visual Motor, and Mobility. A fifth value, Visual Ability, is an aggregate score of the 4 scales, measured in units called logits, and is calculated for each person based on item weighting using Raasch analysis. Visual Ability is used broadly to represent changes in subject-reported outcomes from visit to visit. Higher positive values on the Visual Ability score represent better function and less impairment, whereas lower or negatives scores represent worse function or more impairment. Change in the Visual Ability scale on the VFQ is calculated by taking a subject's score at 12 months and subtracting from it the baseline score.	12 months
Safety of Intravitreal Injection of Retinal Progenitor Cells (RPC)	Assessed by treatment emergent adverse events, immunogenicity and safety visual assessments	12 months

Collaborators and Investigators

• Sponsor: jCyte, Inc
• Collaborators: California Institute for Regenerative Medicine (CIRM)
• Investigators: Principal Investigator: Barruch Kuppermann, MD, UCI

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2017
• Primary Completion (Actual): November 13, 2020
• Study Completion (Actual): November 13, 2020

Study Registration Dates

• First Submitted: March 2, 2017
• First Submitted That Met QC Criteria: March 2, 2017
• First Posted (Actual): March 8, 2017

Study Record Updates

• Last Update Posted (Actual): July 28, 2023
• Last Update Submitted That Met QC Criteria: July 19, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Eye Diseases; Retinal Degeneration; Retinal Diseases; Genetic Diseases, Inborn; Eye Diseases, Hereditary; Retinal Dystrophies; Retinitis; Retinitis Pigmentosa
• Other Study ID Numbers: JC-02

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No