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

• ClinicalTrials.gov Identifier: NCT03073733
• Recruitment Status: Completed
• First Posted: March 8, 2017
• Results First Posted: January 21, 2022
• Last Update Posted: April 4, 2022
• Sponsor: jCyte, Inc
• Collaborator: California Institute for Regenerative Medicine (CIRM)
• Information provided by (Responsible Party): jCyte, Inc

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Retinitis Pigmentosa	Biological: human retinal progenitor cells; Other: Mock injection	Phase 2

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 84 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Outcomes Assessor)
• Masking Description: Subjects, their family members and clinical staff performing key efficacy assessments will be masked to the randomization assignment of subjects. Due to the nature of some safety assessments and the sham treatment, not all personnel can be masked.
• Primary Purpose: Treatment
• Official Title: 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)
• Actual Study Start Date: March 1, 2017
• Actual Primary Completion Date: November 13, 2020
• Actual Study Completion Date: November 13, 2020

Arms and Interventions

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 Name: jCell
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 Name: jCell

Outcome Measures

Primary Outcome Measures :

1. Best Corrected Visual Acuity (BCVA) [ Time Frame: 12 months ]
   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.

Secondary Outcome Measures :

1. Contrast Sensitivity (CS) at 1.0 CPD [ Time Frame: 12 months ]
   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.
2. Kinetic Visual Field (KVF) [ Time Frame: 12 months ]
   Mean change in total area (degrees squared) of all islands of vision from baseline to 12 months.
3. Low Luminance Mobility Test (LLMT) [ Time Frame: 12 months ]
   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.
4. Low Vision Functional Questionnaire (Visual Ability) [ Time Frame: 12 months ]
   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.
5. Safety of Intravitreal Injection of Retinal Progenitor Cells (RPC) [ Time Frame: 12 months ]
   Assessed by treatment emergent adverse events, immunogenicity and safety visual assessments

Eligibility Criteria

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

Criteria

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

Contacts and Locations

Locations

United States, California

Gavin Herbert Eye Inst, Univ Cal Irvine

Irvine, California, United States, 92697

Retina-Vitreous Associates Medical Group

Los Angeles, California, United States, 90074

United States, Massachusetts

Ophthalmic Consultants of Boston

Boston, Massachusetts, United States, 02114

Sponsors and Collaborators

jCyte, Inc

California Institute for Regenerative Medicine (CIRM)

Investigators

• Principal Investigator: Barruch Kuppermann, MD; UCI

  Study Documents (Full-Text)

Documents provided by jCyte, Inc:

Study Protocol  [PDF] October 26, 2017

Statistical Analysis Plan  [PDF] August 8, 2019

More Information

• Responsible Party: jCyte, Inc
• ClinicalTrials.gov Identifier: NCT03073733
• Other Study ID Numbers: JC-02
• First Posted: March 8, 2017
• Results First Posted: January 21, 2022
• Last Update Posted: April 4, 2022
• Last Verified: March 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Retinitis; Retinitis Pigmentosa; Retinal Diseases; Eye Diseases; Eye Diseases, Hereditary; Retinal Dystrophies; Retinal Degeneration; Genetic Diseases, Inborn