Retinitis Pigmentosa
Conditions
Brief summary
The primary objective of the study is to assess the safety of repeat injection of human retinal progenitor cells (jCell) in adult subjects with RP that have previously been treated with jCell.
Detailed description
This is a prospective, multi-center, single arm, Phase 2 study of human retinal progenitor cells (jCell) for the treatment of retinitis pigmentosa (RP). The study will include only subjects previously treated with jCell. To assess reinjection of a previously treated eye, subjects who have previously been treated with jCell and desire a second treatment in the same eye will be enrolled. Subjects must have completed at least 12 months of follow up since the prior injection of jCell. Subjects who have had both eyes previously treated with jCell will only have one eye retreated; the eye to be retreated will preferably be the better seeing eye, but exceptions may be made by the study investigator, taking into consideration BCVA, prior response to treatment, and any other medical conditions that may indicate which eye is the best candidate for retreatment. Subjects will be followed for 12 months for safety and efficacy.
Interventions
BIOLOGICALhuman retinal progenitor cells
single intravitreal injection of 6.0 million human retinal progenitor cells (hRPC)
Sponsors
California Institute for Regenerative Medicine (CIRM)
jCyte, Inc
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Willing to give written informed consent, able to make the required study visits and follow study protocol instructions. 2. Completed the 12 months of follow up in the subject's most recent jCell study and did not withdraw from the study for any reason. 3. Adequate organ function: * blood counts (hematocrit, Hgb, WBC, platelets and differential) within normal range, or if outside of normal range, not clinically significant as judged by the investigator * liver function: alanine transaminase \[ALT\] and aspartate transaminase \[AST\] ≤2 times the upper limit of the normal range * total bilirubin ≤1.5 times the upper limit of the normal range * renal function: serum creatinine ≤1.25 times the upper limit of the normal range 4. A female patient of childbearing potential (not surgically sterilized and less than one year postmenopausal) must have a negative pregnancy test (urine human chorionic gonadotropin) at entry (prior to injection) and must have used medically accepted contraception for at least one month prior to treatment. Women of childbearing potential and men must be advised to use a medically accepted method of contraception for at least 12 months following treatment.
Exclusion criteria
1. Malignancy, end-stage major organ disease (heart failure, significant arrhythmias, stroke or transient ischemic attacks, diabetes, immunosuppressive or autoimmune state, major psychiatric disorder, epilepsy, thyroid disease, COPD, renal failure, or any chronic systemic disease requiring continuous treatment with systemic steroids, anticoagulants or immunosuppressive agents. 2. History of eye disease other than RP that impairs visual function, including retinal vascular disease, elevated intraocular pressure/glaucoma, severe posterior uveitis, clinically significant macular edema, media opacity precluding visual exam, amblyopia and/or longstanding constant strabismus, as well as patients who require other intravitreal therapies 3. Allergy to penicillin or streptomycin. 4. Adverse reaction to DMSO. 5. Unable or unwilling to undergo pupil dilation, topical anesthesia or any protocol-required procedure. 6. Women who are nursing or who are planning to nurse during the 12 months that would follow study treatment. 7. Any circumstance that in the opinion of the investigator, would interfere with participation in, or compliance with the study protocol 8. Treatment with corticosteroids (systemic, periocular or intravitreal) or any other non-approved, experimental, investigational or neuroprotectant therapy (systemic, topical, intravitreal) in either eye within 90 days of planned second injection. 9. Cataract surgery within three months prior to treatment or anticipated to need cataract surgery within a year of treatment
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety of Intravitreal Injection of hRPC | 12 months | Assessed by percentage of subjects with treatment emergent adverse events |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Best Corrected Visual Acuity (BCVA) | 12 months | Mean change in BCVA in study eye from baseline to month 12 as assessed by E-ETDRS. 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. |
| Kinetic Visual Field Area | 12 months | Mean change in total kinetic visual field (KVF) area (degrees squared) of all islands of vision from baseline to 12 months. The Octopus 900 will be used for KVF testing using a specified target of V4e for subjects with a more severely impaired visual field (\<10,000deg2) and a target of III4e and I4e for better seeing subjects (\>10,000deg2). Target size is selected based on the Baseline visit. Whatever target size(s) is/are selected, the same size will be used throughout the study on that particular eye for that particular patient. |
| Contrast Sensitivity (Peak) | 12 months | Contrast sensitivity (CS) measures the ability of a subject to distinguish between finer and finer increments of light versus dark (contrast), as measured with a vertical striped pattern that varies in stripe width (cycles per degree or CPD); CS thresholds are created by taking the mean of multiple trials at each size of the target (i.e., at various CPDs). A CS curve is created by using the threshold of CS means at each target size, with the highest or most sensitive value (regardless of the CPD) representing the peak of the curve (i.e., peak contrast sensitivity). The unit of measure is therefore the peak contrast sensitivity regardless of the target size (i.e., CPD) being used to perform the measurement. The higher the value, the better the ability to detect contrast. The data shown here represent the mean change from Baseline to 12 months in the subjects' peak of the CS curve. |
| Low Luminance Mobility Test (LLMT) | 12 months | The LLMT identifies the performance of 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Retreated Subjects Subjects receiving human retinal progenitor cells (jCell) who have previously received jCell is a jCyte study.
human retinal progenitor cells: single intravitreal injection of 6.0 million human retinal progenitor cells (hRPC) | 30 |
| Total | 30 |
Baseline characteristics
| Characteristic | Retreated Subjects |
|---|---|
| Age, Continuous | 51.6 Years STANDARD_DEVIATION 13.93 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 5 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 25 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Height | 170.14 cm STANDARD_DEVIATION 9.856 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 3 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 26 Participants |
| Sex: Female, Male Female | 13 Participants |
| Sex: Female, Male Male | 17 Participants |
| Study eye Left (OS) | 16 Participants |
| Study eye Right (OD) | 14 Participants |
| Weight | 84.00 kg STANDARD_DEVIATION 24.387 |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 2 / 30 |
| other Total, other adverse events | 6 / 30 |
| serious Total, serious adverse events | 6 / 30 |
Outcome results
Primary
Safety of Intravitreal Injection of hRPC
Assessed by percentage of subjects with treatment emergent adverse events
Time frame: 12 months
Population: Safety population: all subjects who receive any study treatment
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Retreated Subjects | Safety of Intravitreal Injection of hRPC | Subjects with any TEAEs | 15 Participants |
| Retreated Subjects | Safety of Intravitreal Injection of hRPC | Subjects with any TEAEs related/possibly related to study drug | 6 Participants |
| Retreated Subjects | Safety of Intravitreal Injection of hRPC | Subjects with any serious TEAEs | 6 Participants |
| Retreated Subjects | Safety of Intravitreal Injection of hRPC | Subjects with any serious TEAEs related/possibly related to study drug | 2 Participants |
| Retreated Subjects | Safety of Intravitreal Injection of hRPC | Subjects with any severe TEAEs related/possibly related to study drug | 1 Participants |
Secondary
Best Corrected Visual Acuity (BCVA)
Mean change in BCVA in study eye from baseline to month 12 as assessed by E-ETDRS. 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.
Time frame: 12 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Retreated Subjects | Best Corrected Visual Acuity (BCVA) | -2.340 letters correct | Standard Deviation 5.8963 |
Secondary
Contrast Sensitivity (Peak)
Contrast sensitivity (CS) measures the ability of a subject to distinguish between finer and finer increments of light versus dark (contrast), as measured with a vertical striped pattern that varies in stripe width (cycles per degree or CPD); CS thresholds are created by taking the mean of multiple trials at each size of the target (i.e., at various CPDs). A CS curve is created by using the threshold of CS means at each target size, with the highest or most sensitive value (regardless of the CPD) representing the peak of the curve (i.e., peak contrast sensitivity). The unit of measure is therefore the peak contrast sensitivity regardless of the target size (i.e., CPD) being used to perform the measurement. The higher the value, the better the ability to detect contrast. The data shown here represent the mean change from Baseline to 12 months in the subjects' peak of the CS curve.
Time frame: 12 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Retreated Subjects | Contrast Sensitivity (Peak) | -0.57 Arbitrary Units (AU) | Standard Deviation 6.69 |
Secondary
Kinetic Visual Field Area
Mean change in total kinetic visual field (KVF) area (degrees squared) of all islands of vision from baseline to 12 months. The Octopus 900 will be used for KVF testing using a specified target of V4e for subjects with a more severely impaired visual field (\<10,000deg2) and a target of III4e and I4e for better seeing subjects (\>10,000deg2). Target size is selected based on the Baseline visit. Whatever target size(s) is/are selected, the same size will be used throughout the study on that particular eye for that particular patient.
Time frame: 12 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Retreated Subjects | Kinetic Visual Field Area | -493.96 degrees squared | Standard Deviation 1268.067 |
Secondary
Low Luminance Mobility Test (LLMT)
The LLMT identifies the performance of 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.
Time frame: 12 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Retreated Subjects | Low Luminance Mobility Test (LLMT) | -0.1 scores on a scale | Standard Deviation 1.96 |