Retinitis Pigmentosa
Conditions
Keywords
Retinitis Pigmentosa, eye disease, retinal disorder, CNTF
Brief summary
The purpose of this study is to look at the safety and effectiveness of CNTF implants on vision in persons with retinitis pigmentosa, Usher type II & III, and Choroideremia. This research is being done because there are no effective therapies for people with these retinal degenerations. They are genetic disorders that affect one's ability to see at night, and later cause tunnel vision and loss of central vision. Retinal degenerations affect the retina, a light sensitive layer of cells in the back of the eye. Slowly over time, these cells die and cause permanent loss of vision. The implant is a small capsule that contains human retinal pigment epithelium cells. These cells have been given the ability to make CNTF and release it through the capsule membrane into the surrounding fluid. In this study, two different CNTF dose levels will be used: a high dose and a low dose in one eye, as well as a sham (or placebo) surgery in the other eye.
Detailed description
This study will involve about 18 visits over 2½ years for specific tests of the participant's vision and health. These visits may include visual exams, blood draw for laboratory testing, brief medical history and exam, and occasionally a questionnaire (survey), in addition to the visit for the surgical procedures. The primary effectiveness outcome for this study will be a visual field score one year after the implant surgery. There will be about 12 centers participating in this study, and up to 60 people enrolled, across the US. Each participant joining the study who has completed initial screening will then be scheduled to have a brief surgical procedure performed on each eye, one of which will include a very small cell-filled implant. Follow-up visits for repeat assessments will be required regularly to determine if the implant being tested is safe and effective for use to treat retinitis pigmentosa (RP).
Interventions
DRUGNT-501
Low Dose
Sponsors
Neurotech Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 64 Years
Healthy volunteers
No
Inclusion criteria
Study inclusion /
Exclusion criteria
Criteria for patients to qualify for the study include, but are not limited to: * Over 18 years of age, and less than 65 years of age * Diagnosis of retinitis pigmentosa, Usher Syndrome Type 2 or 3 or Choroideremia * Visual acuity no worse than 20/63 * Experience with at least two full threshold Humphrey Visual Field 30-2 tests, one completed within the year prior to enrolling in this study The following criteria will exclude patients from the study: * Pregnant or lactating females, or females planning to become pregnant during the study or not using an acceptable method of contraception. * Retinitis pigmentosa caused by a classic syndrome, including Usher Type I * Other eye diseases including advanced cataract. * Chronic systemic disease requiring continuous treatment with systemic steroids, immunosuppressive medications or insulin.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Humphrey Visual Fields - Total Sensitivity | 12 months | The primary efficacy endpoint was the change in Humphrey VFS from baseline to month 12 (Visit 10) as determined by the HVF 30-2 test, comprised of 76 points. The measure was the sum of actual thresholds for all 76 locations. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Mean Humphrey Visual Fields Sensitivity | Baseline compared to 6, 12, 18, 24 and 30 months | — |
| Mean Humphrey Visual Fields Sensitivity | Baseline compared to 6, 12, 18, 24 and 30 months | Change in Humphrey Visual Field Sensitivity over time |
Countries
United States
Participant flow
Pre-assignment details
A total of 90 participants were screened and 73 were randomized to dose groups. 17 of 90 patients were screen failures and not associated (randomized) to either arm. Of the 73 randomized participants, 5 participants, 2 in the high dose and 3 in the low dose arms were randomized but did not receive surgery and did not take part in the study. 68 participants had surgery. For participants randomized to treatment dose, one eye was randomized to surgery and the fellow eye was randomized to sham.
Participants by arm
| Arm | Count |
|---|---|
| Low Dose - Implant NT-501 Low Dose Implant: encapsulated cell therapy that delivers ciliary neurotrophic factor to the retina | 23 |
| Low Dose - Implant NT-501 Low Dose Implant: encapsulated cell therapy that delivers ciliary neurotrophic factor to the retina | 23 |
| Low Dose - Sham Sham Implant in Fellow Eye (Low Dose Arm) | 23 |
| Low Dose - Sham Sham Implant in Fellow Eye (Low Dose Arm) | 23 |
| High Dose - Implant NT-501 High Dose Implant: encapsulated cell therapy that delivers ciliary neurotrophic factor to the retina | 50 |
| High Dose - Implant NT-501 High Dose Implant: encapsulated cell therapy that delivers ciliary neurotrophic factor to the retina | 50 |
| High Dose - Sham Sham Implant in Fellow Eye (High Dose Arm) | 50 |
| High Dose - Sham Sham Implant in Fellow Eye (High Dose Arm) | 50 |
| Total | 292 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Did not proceed with surgery | 3 | 3 | 2 | 2 |
| Overall Study | Lost to Follow-up | 1 | 1 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 1 | 1 | 4 | 4 |
Baseline characteristics
| Characteristic | Total | Low Dose - Implant | Low Dose - Sham | High Dose - Implant | High Dose - Sham |
|---|---|---|---|---|---|
| Age, Continuous | 37.6 Years STANDARD_DEVIATION 11.9 | 34.9 Years STANDARD_DEVIATION 12 | 34.9 Years STANDARD_DEVIATION 12 | 40.2 Years STANDARD_DEVIATION 11.8 | 40.2 Years STANDARD_DEVIATION 11.8 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 10 Participants | 1 Participants | 1 Participants | 4 Participants | 4 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 136 Participants | 22 Participants | 22 Participants | 46 Participants | 46 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Humphrey Visual Fields - Total Sensitivity (MITT Population) | 1052.5 dB STANDARD_DEVIATION 424.31 | 1142.4 dB STANDARD_DEVIATION 446.33 | 1135.9 dB STANDARD_DEVIATION 423.5 | 969.8 dB STANDARD_DEVIATION 391.74 | 961.7 dB STANDARD_DEVIATION 435.68 |
| Ocular History - Years Since RP Diagnosis | 10.00 years STANDARD_DEVIATION 9.41 | 8.85 years STANDARD_DEVIATION 8.39 | 8.85 years STANDARD_DEVIATION 8.39 | 10.49 years STANDARD_DEVIATION 9.86 | 10.49 years STANDARD_DEVIATION 9.86 |
| Race (NIH/OMB) American Indian or Alaska Native | 2 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 4 Participants | 1 Participants | 1 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 140 Participants | 21 Participants | 21 Participants | 49 Participants | 49 Participants |
| Sex: Female, Male Female | 74 Participants | 11 Participants | 11 Participants | 26 Participants | 26 Participants |
| Sex: Female, Male Male | 72 Participants | 12 Participants | 12 Participants | 24 Participants | 24 Participants |
| Type of Ocular History Ocular disease | 146 Eyes | 23 Eyes | 23 Eyes | 50 Eyes | 50 Eyes |
| Type of Ocular History Ocular surgery | 27 Eyes | 3 Eyes | 3 Eyes | 10 Eyes | 11 Eyes |
| Type of Ocular History Ocular treatment | 6 Eyes | 0 Eyes | 0 Eyes | 2 Eyes | 4 Eyes |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 20 | 0 / 48 |
| other Total, other adverse events | 20 / 20 | 48 / 48 |
| serious Total, serious adverse events | 1 / 20 | 4 / 48 |
Outcome results
Primary
Change in Humphrey Visual Fields - Total Sensitivity
The primary efficacy endpoint was the change in Humphrey VFS from baseline to month 12 (Visit 10) as determined by the HVF 30-2 test, comprised of 76 points. The measure was the sum of actual thresholds for all 76 locations.
Time frame: 12 months
Population: MITT Population excluding 1 participant from the high dose arm who did not complete any visits subsequent to surgery.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Low Dose - Implant | Change in Humphrey Visual Fields - Total Sensitivity | 1.4 dB | Standard Deviation 174.58 |
| Low Dose - Sham | Change in Humphrey Visual Fields - Total Sensitivity | 16.8 dB | Standard Deviation 165.41 |
| High Dose - Implant | Change in Humphrey Visual Fields - Total Sensitivity | -164.8 dB | Standard Deviation 115.02 |
| High Dose - Sham | Change in Humphrey Visual Fields - Total Sensitivity | -66.7 dB | Standard Deviation 103.23 |
Secondary
Change in Mean Humphrey Visual Fields Sensitivity
Time frame: Baseline compared to 6, 12, 18, 24 and 30 months
Population: MITT Population excluding 1 participant from the high dose arm who did not complete any visits subsequent to surgery.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Low Dose - Implant | Change in Mean Humphrey Visual Fields Sensitivity | 6 Months - Change from BL | -1.21 dB | Standard Deviation 140.09 |
| Low Dose - Implant | Change in Mean Humphrey Visual Fields Sensitivity | 12 Months - Change from BL | 1.35 dB | Standard Deviation 174.58 |
| Low Dose - Implant | Change in Mean Humphrey Visual Fields Sensitivity | 18 Months - Change from BL | -62.65 dB | Standard Deviation 208.64 |
| Low Dose - Implant | Change in Mean Humphrey Visual Fields Sensitivity | 24 Months - Change from BL | -104.15 dB | Standard Deviation 194.5 |
| Low Dose - Implant | Change in Mean Humphrey Visual Fields Sensitivity | 30 Months (retained implant) - Change from BL | -46.977 dB | Standard Deviation 345.78 |
| Low Dose - Implant | Change in Mean Humphrey Visual Fields Sensitivity | 30 Months (6 Months Post-Explant) - Change from BL | -82.67 dB | Standard Deviation 185.6 |
| Low Dose - Sham | Change in Mean Humphrey Visual Fields Sensitivity | 30 Months (6 Months Post-Explant) - Change from BL | -58.50 dB | Standard Deviation 148.57 |
| Low Dose - Sham | Change in Mean Humphrey Visual Fields Sensitivity | 24 Months - Change from BL | -72.15 dB | Standard Deviation 162.72 |
| Low Dose - Sham | Change in Mean Humphrey Visual Fields Sensitivity | 6 Months - Change from BL | 25.80 dB | Standard Deviation 128.34 |
| Low Dose - Sham | Change in Mean Humphrey Visual Fields Sensitivity | 18 Months - Change from BL | -37.33 dB | Standard Deviation 173.46 |
| Low Dose - Sham | Change in Mean Humphrey Visual Fields Sensitivity | 12 Months - Change from BL | 16.75 dB | Standard Deviation 165.41 |
| Low Dose - Sham | Change in Mean Humphrey Visual Fields Sensitivity | 30 Months (retained implant) - Change from BL | -58.64 dB | Standard Deviation 275.09 |
| High Dose - Implant | Change in Mean Humphrey Visual Fields Sensitivity | 12 Months - Change from BL | -164.79 dB | Standard Deviation 115.02 |
| High Dose - Implant | Change in Mean Humphrey Visual Fields Sensitivity | 18 Months - Change from BL | -202.31 dB | Standard Deviation 137.13 |
| High Dose - Implant | Change in Mean Humphrey Visual Fields Sensitivity | 24 Months - Change from BL | -227.89 dB | Standard Deviation 149.73 |
| High Dose - Implant | Change in Mean Humphrey Visual Fields Sensitivity | 30 Months (6 Months Post-Explant) - Change from BL | -188.64 dB | Standard Deviation 122.33 |
| High Dose - Implant | Change in Mean Humphrey Visual Fields Sensitivity | 30 Months (retained implant) - Change from BL | -321.72 dB | Standard Deviation 196.81 |
| High Dose - Implant | Change in Mean Humphrey Visual Fields Sensitivity | 6 Months - Change from BL | -135.23 dB | Standard Deviation 107.86 |
| High Dose - Sham | Change in Mean Humphrey Visual Fields Sensitivity | 30 Months (retained implant) - Change from BL | -211.82 dB | Standard Deviation 145.25 |
| High Dose - Sham | Change in Mean Humphrey Visual Fields Sensitivity | 30 Months (6 Months Post-Explant) - Change from BL | -144.60 dB | Standard Deviation 134.31 |
| High Dose - Sham | Change in Mean Humphrey Visual Fields Sensitivity | 12 Months - Change from BL | -66.65 dB | Standard Deviation 103.23 |
| High Dose - Sham | Change in Mean Humphrey Visual Fields Sensitivity | 24 Months - Change from BL | -136.96 dB | Standard Deviation 126.73 |
| High Dose - Sham | Change in Mean Humphrey Visual Fields Sensitivity | 6 Months - Change from BL | -42.99 dB | Standard Deviation 82.85 |
| High Dose - Sham | Change in Mean Humphrey Visual Fields Sensitivity | 18 Months - Change from BL | -98.73 dB | Standard Deviation 127.09 |
Secondary
Mean Humphrey Visual Fields Sensitivity
Change in Humphrey Visual Field Sensitivity over time
Time frame: Baseline compared to 6, 12, 18, 24 and 30 months
Population: MITT Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Low Dose - Implant | Mean Humphrey Visual Fields Sensitivity | 6 Months | 1141.21 dB | Standard Deviation 438.07 |
| Low Dose - Implant | Mean Humphrey Visual Fields Sensitivity | 24 Months | 1038.28 dB | Standard Deviation 430.12 |
| Low Dose - Implant | Mean Humphrey Visual Fields Sensitivity | Baseline | 1142.43 dB | Standard Deviation 446.33 |
| Low Dose - Implant | Mean Humphrey Visual Fields Sensitivity | 30 Months with retained implant | 1176.22 dB | Standard Deviation 384.29 |
| Low Dose - Implant | Mean Humphrey Visual Fields Sensitivity | 12 Months | 1143.78 dB | Standard Deviation 409.76 |
| Low Dose - Implant | Mean Humphrey Visual Fields Sensitivity | 30 Months (6 Months Post-Explant) | 1090.92 dB | Standard Deviation 382.1 |
| Low Dose - Implant | Mean Humphrey Visual Fields Sensitivity | 18 Months | 1079.78 dB | Standard Deviation 440.81 |
| Low Dose - Sham | Mean Humphrey Visual Fields Sensitivity | Baseline | 1135.94 dB | Standard Deviation 423.5 |
| Low Dose - Sham | Mean Humphrey Visual Fields Sensitivity | 12 Months | 1152.69 dB | Standard Deviation 388.3 |
| Low Dose - Sham | Mean Humphrey Visual Fields Sensitivity | 24 Months | 1063.79 dB | Standard Deviation 398.68 |
| Low Dose - Sham | Mean Humphrey Visual Fields Sensitivity | 30 Months (6 Months Post-Explant) | 1056.08 dB | Standard Deviation 406.65 |
| Low Dose - Sham | Mean Humphrey Visual Fields Sensitivity | 6 Months | 1161.74 dB | Standard Deviation 399.67 |
| Low Dose - Sham | Mean Humphrey Visual Fields Sensitivity | 18 Months | 1098.61 dB | Standard Deviation 427.23 |
| Low Dose - Sham | Mean Humphrey Visual Fields Sensitivity | 30 Months with retained implant | 1173.32 dB | Standard Deviation 340.09 |
| High Dose - Implant | Mean Humphrey Visual Fields Sensitivity | Baseline | 969.83 dB | Standard Deviation 391.74 |
| High Dose - Implant | Mean Humphrey Visual Fields Sensitivity | 6 Months | 834.60 dB | Standard Deviation 354.98 |
| High Dose - Implant | Mean Humphrey Visual Fields Sensitivity | 30 Months (6 Months Post-Explant) | 752.78 dB | Standard Deviation 345.78 |
| High Dose - Implant | Mean Humphrey Visual Fields Sensitivity | 12 Months | 805.03 dB | Standard Deviation 357.86 |
| High Dose - Implant | Mean Humphrey Visual Fields Sensitivity | 30 Months with retained implant | 695.97 dB | Standard Deviation 251.57 |
| High Dose - Implant | Mean Humphrey Visual Fields Sensitivity | 18 Months | 757.80 dB | Standard Deviation 363.86 |
| High Dose - Implant | Mean Humphrey Visual Fields Sensitivity | 24 Months | 745.62 dB | Standard Deviation 344.58 |
| High Dose - Sham | Mean Humphrey Visual Fields Sensitivity | Baseline | 961.70 dB | Standard Deviation 435.68 |
| High Dose - Sham | Mean Humphrey Visual Fields Sensitivity | 6 Months | 918.72 dB | Standard Deviation 422.6 |
| High Dose - Sham | Mean Humphrey Visual Fields Sensitivity | 12 Months | 895.05 dB | Standard Deviation 427.12 |
| High Dose - Sham | Mean Humphrey Visual Fields Sensitivity | 18 Months | 850.92 dB | Standard Deviation 404.91 |
| High Dose - Sham | Mean Humphrey Visual Fields Sensitivity | 24 Months | 825.06 dB | Standard Deviation 396.47 |
| High Dose - Sham | Mean Humphrey Visual Fields Sensitivity | 30 Months with retained implant | 787.30 dB | Standard Deviation 322.72 |
| High Dose - Sham | Mean Humphrey Visual Fields Sensitivity | 30 Months (6 Months Post-Explant) | 782.60 dB | Standard Deviation 382.68 |