Retinoschisis, X-Linked
Conditions
Keywords
Gene Transfer, X-Linked, Retinoschisis, AAV Vector
Brief summary
Background: \- X-linked juvenile retinoschisis (XLRS) is caused by changes in the RS1 gene. These changes cause abnormal function of the eye protein retinoschisin. Without normal retinoschisin, the layers of the retina split and vision is lost. Researchers want to try to introduce a healthy RS1 gene into eye cells, to see if this helps retinal cells make healthy retinoschisin. They will put the gene in a virus. The gene and virus package is known as a gene transfer vector (AAV-RS1 vector). Objectives: \- To see if the AAV-RS1 vector is safe to use in patients with X-linked retinoschisis. Eligibility: \- Adults 18 and older with a mutation of the RS1 gene, 20/63 vision or worse in one eye, and XLRS. Design: * Participants will be screened with genetic tests to confirm XLRS. They will have a medical history and physical and eye exams. * At visits 1-2, participants will have some or all of the following: * Medical history * Physical exam * Blood and urine tests * Tuberculosis skin test * Eye exam * Vision tests (for one test an intravenous line will be placed in the arm. A dye will be injected that will travel to the blood vessels in the eye). * At visit 3, the AAV-RS1 vector will be injected with a needle in the study eye. Participants pupils will be dilated. They will get numbing eye drops. * Visits 4-13 will occur in the 18 months after gene transfer. Many of the above tests will be repeated. Participants will discuss any side effects. * Visits 14-17 will occur yearly between years 2 and 5. * After year 5, participants will be contacted yearly by phone for up to 15 years.
Detailed description
Objective: To evaluate the safety and tolerability of ocular AAV-RS1 vector (AAV8-scRS/IRBPhRS) gene transfer to the retina of participants affected with X-linked juvenile retinoschisis (XLRS). Study Population: Male participants affected with XLRS will receive ocular gene transfer. A maximum of up to 24 participants may be enrolled. Design: This is a Phase I/IIa, prospective, dose escalation, single-center study. One eye of each participant will receive the AAV-RS1 gene vector application by intravitreal injection. Participants will be closely monitored in conjunction with DSMC oversight. Participants will be followed for 18 months after which they will continue to be followed for up to 5 years after enrollment, or per FDA requirements, for further safety analysis. Outcome Measures: The primary outcome is the safety of ocular AAV-RS1 vector as determined from assessment of retinal function, ocular structure and occurrence of adverse events and laboratory tests. Secondary outcomes include changes in visual function, electroretinogram (ERG) responses, visual field measurements, retinal imaging with optical coherence tomography (OCT), and the formation of anti-AAV and anti-RS1 antibodies. Statistics: No formal sample size calculations are used in this Phase I/IIa dose-escalation study.
Interventions
BIOLOGICALRS1 AAV Vector
Gene transfer by intravitreal injection of the RS1 AAV vector (AAV8-scRS/IRBPhRS)
Sponsors
National Eye Institute (NEI)
VegaVect, Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Participant is male with a mutation in the RS1 gene identified by genotyping. * Participant must be 18 years of age or older. * Participant must be able to understand and sign the informed consent. * Participant must be medically able to comply with the study treatment, study testing and procedures and follow-up visits. * Participant has at least one eye that meets the study eye criteria listed below. * Participant must agree to use effective barrier (male or female condom) of contraception starting two weeks before and continuing one year after gene transfer. * If the participant's partner is able to become pregnant, a second form of effective contraception will be required starting two weeks before and continuing one year after gene transfer. Effective methods of contraception for this study include: * hormonal contraception (birth control pills, injected hormones or vaginal ring), * intrauterine device, * barrier methods (condom or diaphragm) combined with spermicide, * surgical sterilization (hysterectomy or tubal ligation in partner or vasectomy).
Exclusion criteria
* Participant is actively receiving another study medication/investigational product (IP). * Participant has previously enrolled in another gene therapy trial. * Participant is currently taking, or has taken in the last three months, a systemic carbonic anhydrase inhibitor prior to enrollment/baseline 1 testing. * Participant has any condition that significantly increases risk of systemic corticosteroids or systemic steroid-sparing immuno-modulatory agents, such as HIV, syphilis, tuberculosis, hepatitis B, hepatitis C, or diabetes mellitus (DM). * Participant has an underlying serious illness that impairs regular follow-up during the study. * Participant has had diagnosis or treatment of a malignancy (excluding non-melanoma skin cancer) within the previous five years. * Participant has pre-existing ocular tumors (excluding non-suspicious nevi). * Participant has a known allergy to fluorescein dye or other contraindications to obtaining a fluorescein angiogram. * Participant is on a medication that prevents safe administration of study related drugs. * Participant has uncontrolled hypertension. (Hypertension judged to be adequately controlled at baseline medical evaluation is not exclusionary.) * Participant has compromised renal function such that cyclosporine or Cellcept, which could be used to treat any manifest ocular inflammation, would be contraindicated. * Participant has significant liver disease with elevated liver enzymes (greater than or equal to 2.5 times upper limit of normal \[ULN\]). * Participant has low absolute neutrophil count (ANC\<1.3 x 10(3)/micro liters). * Participant has used any biologic immunosuppressive agents within the last three months (within the last six months for rituximab or cyclophosphamide). STUDY EYE ELIGIBILITY CRITERIA: The participant must have at least one eye meeting all inclusion criteria and none of the
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Adverse Events (AEs) Affecting Ocular Function That Differ Clinically From Those Expected in the Normal Course of Progression of XLRS | Day 0 through Year 2, inclusive | Includes a) substantial functional change (change \>=10 electronic visual acuity letters in best-corrected visual acuity from average of baseline visits), b) decrease in electroretinogram response amplitude (\>=75% from average of baseline visits), c) severe ocular inflammation beyond inflammation anticipated consequent to an intravitreal injection; d) adverse events deemed clinically-related to the intraocular administration technique, and e) abnormal laboratory findings beyond Grade 1 Common Terminology Criteria for Adverse Events v5.0 and/or clinically significantly different than baseline. a)-d) only includes events occurring in the study eye. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change in Best Corrected Visual Acuity | Baseline 1 through Year 2 | Mean change in best corrected visual acuity (BCVA) at Year 2 compared to average of baseline 1 and 2. BCVA is measured via Electronic Visual Acuity (EVA). |
| Median and Distribution of Change in Best-Corrected Visual Acuity | Baseline 1 through Year 2 | Median and distribution of change in best-corrected visual acuity (BCVA) at Year 2 compared to average of baseline 1 and 2. BCVA is measured via Electronic Visual Acuity (EVA). |
| Change in Electroretinography Combined Response Amplitudes | Baseline 1 through Year 2 | Change in electroretinography combined response amplitudes from average of baseline 1 and 2 measurements. The higher the amplitude, the better. |
| Change in Retinal Structure as Measured by Optical Coherence Tomography | Baseline 1 through end of study participation (Year 5 or Year 7) | Change in retinal structure as measured by optical coherence tomography (OCT) compared to average of baseline 1 and 2. Includes a) quantitative measures of total retinal thickness obtained with the Cirrus OCT using macular cube scans, b) qualitative morphologic changes to macula anatomy investigated using the tracking ability of the Heidelberg Spectralis OCT system and c) length of intact ellipsoid zone on the OCT and any findings of restoration of this reflectivity line. |
| Change in Central Visual Field Sensitivity as Measured by Microperimetry (MP-1) Visual Field Testing | Baseline 1 through end of study participation (Year 5 or Year 7) | Change in central visual field sensitivity as measured by microperimetry (MP-1) Visual Field testing compared to average of baseline 1 and 2. Includes mean sensitivities, number of scotomatous points and number of points with a significant change in sensitivity. |
| Formation of Circulating Systemic Anti-AAV or Anti-RS1 Antibodies | Day 0 through end of study participation (Year 5 or Year 7) | Formation of circulating systemic anti-AAV or anti-RS1 antibodies assessed via serologic testing |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Cohort 1 1e9 vg/eye
RS1 AAV Vector: Gene transfer by intravitreal injection of the RS1 AAV vector (AAV8-scRS/IRBPhRS) | 3 |
| Cohort 1 1e9 vg/eye
RS1 AAV Vector: Gene transfer by intravitreal injection of the RS1 AAV vector (AAV8-scRS/IRBPhRS) | 6 |
| Cohort 2 1e10 vg/eye
RS1 AAV Vector: Gene transfer by intravitreal injection of the RS1 AAV vector (AAV8-scRS/IRBPhRS) | 3 |
| Cohort 2 1e10 vg/eye
RS1 AAV Vector: Gene transfer by intravitreal injection of the RS1 AAV vector (AAV8-scRS/IRBPhRS) | 6 |
| Cohort 3 1e11 vg/eye
RS1 AAV Vector: Gene transfer by intravitreal injection of the RS1 AAV vector (AAV8-scRS/IRBPhRS) | 3 |
| Cohort 3 1e11 vg/eye
RS1 AAV Vector: Gene transfer by intravitreal injection of the RS1 AAV vector (AAV8-scRS/IRBPhRS) | 6 |
| Cohort 4 1e11 vg/eye
RS1 AAV Vector: Gene transfer by intravitreal injection of the RS1 AAV vector (AAV8-scRS/IRBPhRS) | 2 |
| Cohort 4 1e11 vg/eye
RS1 AAV Vector: Gene transfer by intravitreal injection of the RS1 AAV vector (AAV8-scRS/IRBPhRS) | 4 |
| Cohort 5 3e11 vg/eye
RS1 AAV Vector: Gene transfer by intravitreal injection of the RS1 AAV vector (AAV8-scRS/IRBPhRS) | 1 |
| Cohort 5 3e11 vg/eye
RS1 AAV Vector: Gene transfer by intravitreal injection of the RS1 AAV vector (AAV8-scRS/IRBPhRS) | 2 |
| Cohort 6 Not to exceed 6e11 vg/eye
RS1 AAV Vector: Gene transfer by intravitreal injection of the RS1 AAV vector (AAV8-scRS/IRBPhRS) | 0 |
| Cohort 6 Not to exceed 6e11 vg/eye
RS1 AAV Vector: Gene transfer by intravitreal injection of the RS1 AAV vector (AAV8-scRS/IRBPhRS) | 0 |
| Total | 36 |
Baseline characteristics
| Characteristic | Cohort 2 | Cohort 1 | Cohort 3 | Cohort 4 | Cohort 5 | Cohort 6 | Total |
|---|---|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Age, Categorical Between 18 and 65 years | 3 Participants | 2 Participants | 3 Participants | 2 Participants | 1 Participants | 0 Participants | 11 Participants |
| Age, Continuous | 47.7 years STANDARD_DEVIATION 11.9 | 58.7 years STANDARD_DEVIATION 11.5 | 36.3 years STANDARD_DEVIATION 12.2 | 41.0 years STANDARD_DEVIATION 5.7 | 38.0 years | — | 45.7 years STANDARD_DEVIATION 12.7 |
| Best Corrected Visual Acuity Fellow Eye | 59.5 letters read STANDARD_DEVIATION 6.9 | 51.8 letters read STANDARD_DEVIATION 4.9 | 66.2 letters read STANDARD_DEVIATION 4.1 | 66.3 letters read STANDARD_DEVIATION 8.8 | 68.0 letters read | — | 61.1 letters read STANDARD_DEVIATION 8 |
| Best Corrected Visual Acuity Study Eye | 45.8 letters read STANDARD_DEVIATION 16.5 | 43.7 letters read STANDARD_DEVIATION 8.5 | 48.7 letters read STANDARD_DEVIATION 8.4 | 52.0 letters read STANDARD_DEVIATION 2.8 | 61.0 letters read | — | 48.3 letters read STANDARD_DEVIATION 10 |
| Electroretinography Combined Response Amplitudes Dark-Adapted Combined Rod-Cone A-Wave 0dB Amplitude: Fellow Eye | 176.5 µv STANDARD_DEVIATION 75.8 | 180.2 µv STANDARD_DEVIATION 60.8 | 190.5 µv STANDARD_DEVIATION 21.9 | 186.8 µv STANDARD_DEVIATION 23.7 | 235 µv | — | 187.5 µv STANDARD_DEVIATION 45.9 |
| Electroretinography Combined Response Amplitudes Dark-Adapted Combined Rod-Cone A-Wave 0dB Amplitude: Study Eye | 222.5 µv STANDARD_DEVIATION 48 | 166.8 µv STANDARD_DEVIATION 38.6 | 201.3 µv STANDARD_DEVIATION 17.5 | 162.5 µv STANDARD_DEVIATION 8.5 | 211.5 µv | — | 192.4 µv STANDARD_DEVIATION 37.3 |
| Electroretinography Combined Response Amplitudes Dark-Adapted Combined Rod-Cone A-Wave 11dB Amplitude: Fellow Eye | 244.8 µv STANDARD_DEVIATION 96.2 | 276.2 µv STANDARD_DEVIATION 89 | 259.5 µv STANDARD_DEVIATION 15.1 | 269.8 µv STANDARD_DEVIATION 64 | 301.5 µv | — | 265.2 µv STANDARD_DEVIATION 61.8 |
| Electroretinography Combined Response Amplitudes Dark-Adapted Combined Rod-Cone A-Wave 11dB Amplitude: Study Eye | 298.5 µv STANDARD_DEVIATION 57 | 260.0 µv STANDARD_DEVIATION 46.8 | 297.0 µv STANDARD_DEVIATION 17.5 | 258.3 µv STANDARD_DEVIATION 34.3 | 272.5 µv | — | 279.6 µv STANDARD_DEVIATION 39 |
| Electroretinography Combined Response Amplitudes Dark-Adapted Combined Rod-Cone B-Wave 0dB Amplitude: Fellow Eye | 134.3 µv STANDARD_DEVIATION 21.6 | 138.2 µv STANDARD_DEVIATION 66.6 | 138.2 µv STANDARD_DEVIATION 24.8 | 137.25 µv STANDARD_DEVIATION 42.1 | 294 µv | — | 150.0 µv STANDARD_DEVIATION 56.8 |
| Electroretinography Combined Response Amplitudes Dark-Adapted Combined Rod-Cone B-Wave 0dB Amplitude: Study Eye | 175.2 µv STANDARD_DEVIATION 22.8 | 122.5 µv STANDARD_DEVIATION 60.7 | 142.5 µv STANDARD_DEVIATION 17.1 | 125.8 µv STANDARD_DEVIATION 34.3 | 243.0 µv | — | 151.3 µv STANDARD_DEVIATION 47 |
| Electroretinography Combined Response Amplitudes Dark-Adapted Combined Rod-Cone B-Wave 11dB Amplitude: Fellow Eye | 171.5 µv STANDARD_DEVIATION 15.5 | 197.8 µv STANDARD_DEVIATION 73.3 | 184.3 µv STANDARD_DEVIATION 23.3 | 184.8 µv STANDARD_DEVIATION 64 | 313.0 µv | — | 195.3 µv STANDARD_DEVIATION 54.4 |
| Electroretinography Combined Response Amplitudes Dark-Adapted Combined Rod-Cone B-Wave 11dB Amplitude: Study Eye | 202.5 µv STANDARD_DEVIATION 19.3 | 175.0 µv STANDARD_DEVIATION 67.2 | 193.3 µv STANDARD_DEVIATION 10.9 | 175.0 µv STANDARD_DEVIATION 62.2 | 288.0 µv | — | 195.9 µv STANDARD_DEVIATION 47.4 |
| Electroretinography Combined Response Amplitudes Dark-Adapted Oscillatory Potentials Amplitude: Fellow Eye | 19.5 µv STANDARD_DEVIATION 5.6 | 13.7 µv STANDARD_DEVIATION 5.4 | 22.2 µv STANDARD_DEVIATION 18.6 | 26.5 µv STANDARD_DEVIATION 20.5 | 61.5 µv | — | 23.4 µv STANDARD_DEVIATION 16.6 |
| Electroretinography Combined Response Amplitudes Dark-Adapted Oscillatory Potentials Amplitude: Study Eye | 25.2 µv STANDARD_DEVIATION 11 | 13.8 µv STANDARD_DEVIATION 7.3 | 19.3 µv STANDARD_DEVIATION 12.4 | 23.3 µv STANDARD_DEVIATION 15.2 | 46.0 µv | — | 22.3 µv STANDARD_DEVIATION 12.5 |
| Electroretinography Combined Response Amplitudes Dark-Adapted Rod Amplitude: Fellow Eye | 46.3 µv STANDARD_DEVIATION 4.8 | 73.8 µv STANDARD_DEVIATION 50.2 | 70.3 µv STANDARD_DEVIATION 31.5 | 73.8 µv STANDARD_DEVIATION 14.5 | 149.5 µv | — | 72.4 µv STANDARD_DEVIATION 37.3 |
| Electroretinography Combined Response Amplitudes Dark-Adapted Rod Amplitude: Study Eye | 64.7 µv STANDARD_DEVIATION 34.6 | 51.5 µv STANDARD_DEVIATION 40.7 | 57.2 µv STANDARD_DEVIATION 8.7 | 75.0 µv STANDARD_DEVIATION 25.5 | 130.0 µv | — | 66.7 µv STANDARD_DEVIATION 32.5 |
| Electroretinography Combined Response Amplitudes Light-Adapted Cone A-Wave 11dB Amplitude: Fellow Eye | 66.5 µv STANDARD_DEVIATION 9.6 | 59.2 µv STANDARD_DEVIATION 23.3 | 70.7 µv STANDARD_DEVIATION 23.9 | 65.5 µv STANDARD_DEVIATION 24.7 | 63.0 µv | — | 65.3 µv STANDARD_DEVIATION 17.2 |
| Electroretinography Combined Response Amplitudes Light-Adapted Cone A-Wave 11dB Amplitude: Study Eye | 75.5 µv STANDARD_DEVIATION 13.7 | 57.2 µv STANDARD_DEVIATION 10.1 | 76.5 µv STANDARD_DEVIATION 8.5 | 68.5 µv STANDARD_DEVIATION 14.1 | 66.5 µv | — | 69.3 µv STANDARD_DEVIATION 12.2 |
| Electroretinography Combined Response Amplitudes Light-Adapted Cone B-Wave 0dB Amplitude: Fellow Eye | 57.8 µv STANDARD_DEVIATION 13.7 | 46.8 µv STANDARD_DEVIATION 22.5 | 66.3 µv STANDARD_DEVIATION 23.3 | 75.0 µv STANDARD_DEVIATION 48.8 | 106.0 µv | — | 64.1 µv STANDARD_DEVIATION 26.8 |
| Electroretinography Combined Response Amplitudes Light-Adapted Cone B-Wave 0dB Amplitude: Study Eye | 66.2 µv STANDARD_DEVIATION 22.8 | 39.3 µv STANDARD_DEVIATION 23.6 | 60.7 µv STANDARD_DEVIATION 14.5 | 62.5 µv STANDARD_DEVIATION 41 | 97.5 µv | — | 60.1 µv STANDARD_DEVIATION 25.4 |
| Electroretinography Combined Response Amplitudes Light-Adapted Flicker Amplitude: Fellow Eye | 47.8 µv STANDARD_DEVIATION 13.3 | 37.5 µv STANDARD_DEVIATION 12.1 | 52.7 µv STANDARD_DEVIATION 26.6 | 63.0 µv STANDARD_DEVIATION 38.2 | 82.5 µv | — | 51.9 µv STANDARD_DEVIATION 22.1 |
| Electroretinography Combined Response Amplitudes Light-Adapted Flicker Amplitude: Study Eye | 55.8 µv STANDARD_DEVIATION 25.3 | 33.8 µv STANDARD_DEVIATION 15.3 | 46.2 µv STANDARD_DEVIATION 11.5 | 55.8 µv STANDARD_DEVIATION 25.8 | 76.0 µv | — | 49.6 µv STANDARD_DEVIATION 19.9 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants | — | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 3 Participants | 2 Participants | 3 Participants | 2 Participants | 0 Participants | — | 10 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | — | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | — | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | — | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 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 | — | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 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 | — | 0 Participants |
| Race (NIH/OMB) White | 3 Participants | 3 Participants | 3 Participants | 2 Participants | 1 Participants | — | 12 Participants |
| Region of Enrollment United States | 3 Participants | 3 Participants | 3 Participants | 2 Participants | 1 Participants | — | 12 Participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | — | 0 Participants |
| Sex: Female, Male Male | 3 Participants | 3 Participants | 3 Participants | 2 Participants | 1 Participants | — | 12 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 3 | 0 / 3 | 0 / 3 | 0 / 2 | 0 / 1 | 0 / 0 |
| other Total, other adverse events | 3 / 3 | 3 / 3 | 3 / 3 | 2 / 2 | 1 / 1 | 0 / 0 |
| serious Total, serious adverse events | 1 / 3 | 0 / 3 | 2 / 3 | 0 / 2 | 1 / 1 | 0 / 0 |
Outcome results
Primary
Adverse Events (AEs) Affecting Ocular Function That Differ Clinically From Those Expected in the Normal Course of Progression of XLRS
Includes a) substantial functional change (change \>=10 electronic visual acuity letters in best-corrected visual acuity from average of baseline visits), b) decrease in electroretinogram response amplitude (\>=75% from average of baseline visits), c) severe ocular inflammation beyond inflammation anticipated consequent to an intravitreal injection; d) adverse events deemed clinically-related to the intraocular administration technique, and e) abnormal laboratory findings beyond Grade 1 Common Terminology Criteria for Adverse Events v5.0 and/or clinically significantly different than baseline. a)-d) only includes events occurring in the study eye.
Time frame: Day 0 through Year 2, inclusive
Population: Includes all participants enrolled in the study and were administered the AAV vector injection, regardless of follow-up.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cohort 1 | Adverse Events (AEs) Affecting Ocular Function That Differ Clinically From Those Expected in the Normal Course of Progression of XLRS | Substantial functional change (Day 0-Year 2) | 0 events |
| Cohort 1 | Adverse Events (AEs) Affecting Ocular Function That Differ Clinically From Those Expected in the Normal Course of Progression of XLRS | AEs affecting ocular function (differ clinically from expected in normal progression of XLRS) | 3 events |
| Cohort 1 | Adverse Events (AEs) Affecting Ocular Function That Differ Clinically From Those Expected in the Normal Course of Progression of XLRS | Severe Ocular Inflammation (Day 8-Year 2) | 0 events |
| Cohort 1 | Adverse Events (AEs) Affecting Ocular Function That Differ Clinically From Those Expected in the Normal Course of Progression of XLRS | AEs Clinically Related to Intraocular Administration Technique (Day 8-Year 2) | 0 events |
| Cohort 1 | Adverse Events (AEs) Affecting Ocular Function That Differ Clinically From Those Expected in the Normal Course of Progression of XLRS | Decrease in Electroretinogram Response Amplitude (Day 0-Year 2) | 0 events |
| Cohort 1 | Adverse Events (AEs) Affecting Ocular Function That Differ Clinically From Those Expected in the Normal Course of Progression of XLRS | Abnormal Laboratory Findings (Day 0-Year 2) | 3 events |
| Cohort 2 | Adverse Events (AEs) Affecting Ocular Function That Differ Clinically From Those Expected in the Normal Course of Progression of XLRS | Decrease in Electroretinogram Response Amplitude (Day 0-Year 2) | 0 events |
| Cohort 2 | Adverse Events (AEs) Affecting Ocular Function That Differ Clinically From Those Expected in the Normal Course of Progression of XLRS | Severe Ocular Inflammation (Day 8-Year 2) | 0 events |
| Cohort 2 | Adverse Events (AEs) Affecting Ocular Function That Differ Clinically From Those Expected in the Normal Course of Progression of XLRS | Abnormal Laboratory Findings (Day 0-Year 2) | 1 events |
| Cohort 2 | Adverse Events (AEs) Affecting Ocular Function That Differ Clinically From Those Expected in the Normal Course of Progression of XLRS | Substantial functional change (Day 0-Year 2) | 0 events |
| Cohort 2 | Adverse Events (AEs) Affecting Ocular Function That Differ Clinically From Those Expected in the Normal Course of Progression of XLRS | AEs Clinically Related to Intraocular Administration Technique (Day 8-Year 2) | 2 events |
| Cohort 2 | Adverse Events (AEs) Affecting Ocular Function That Differ Clinically From Those Expected in the Normal Course of Progression of XLRS | AEs affecting ocular function (differ clinically from expected in normal progression of XLRS) | 3 events |
| Cohort 3 | Adverse Events (AEs) Affecting Ocular Function That Differ Clinically From Those Expected in the Normal Course of Progression of XLRS | Substantial functional change (Day 0-Year 2) | 3 events |
| Cohort 3 | Adverse Events (AEs) Affecting Ocular Function That Differ Clinically From Those Expected in the Normal Course of Progression of XLRS | AEs affecting ocular function (differ clinically from expected in normal progression of XLRS) | 12 events |
| Cohort 3 | Adverse Events (AEs) Affecting Ocular Function That Differ Clinically From Those Expected in the Normal Course of Progression of XLRS | Decrease in Electroretinogram Response Amplitude (Day 0-Year 2) | 0 events |
| Cohort 3 | Adverse Events (AEs) Affecting Ocular Function That Differ Clinically From Those Expected in the Normal Course of Progression of XLRS | Severe Ocular Inflammation (Day 8-Year 2) | 0 events |
| Cohort 3 | Adverse Events (AEs) Affecting Ocular Function That Differ Clinically From Those Expected in the Normal Course of Progression of XLRS | AEs Clinically Related to Intraocular Administration Technique (Day 8-Year 2) | 8 events |
| Cohort 3 | Adverse Events (AEs) Affecting Ocular Function That Differ Clinically From Those Expected in the Normal Course of Progression of XLRS | Abnormal Laboratory Findings (Day 0-Year 2) | 1 events |
| Cohort 4 | Adverse Events (AEs) Affecting Ocular Function That Differ Clinically From Those Expected in the Normal Course of Progression of XLRS | Substantial functional change (Day 0-Year 2) | 0 events |
| Cohort 4 | Adverse Events (AEs) Affecting Ocular Function That Differ Clinically From Those Expected in the Normal Course of Progression of XLRS | Abnormal Laboratory Findings (Day 0-Year 2) | 4 events |
| Cohort 4 | Adverse Events (AEs) Affecting Ocular Function That Differ Clinically From Those Expected in the Normal Course of Progression of XLRS | AEs affecting ocular function (differ clinically from expected in normal progression of XLRS) | 6 events |
| Cohort 4 | Adverse Events (AEs) Affecting Ocular Function That Differ Clinically From Those Expected in the Normal Course of Progression of XLRS | AEs Clinically Related to Intraocular Administration Technique (Day 8-Year 2) | 2 events |
| Cohort 4 | Adverse Events (AEs) Affecting Ocular Function That Differ Clinically From Those Expected in the Normal Course of Progression of XLRS | Decrease in Electroretinogram Response Amplitude (Day 0-Year 2) | 0 events |
| Cohort 4 | Adverse Events (AEs) Affecting Ocular Function That Differ Clinically From Those Expected in the Normal Course of Progression of XLRS | Severe Ocular Inflammation (Day 8-Year 2) | 0 events |
| Cohort 5 | Adverse Events (AEs) Affecting Ocular Function That Differ Clinically From Those Expected in the Normal Course of Progression of XLRS | Abnormal Laboratory Findings (Day 0-Year 2) | 0 events |
| Cohort 5 | Adverse Events (AEs) Affecting Ocular Function That Differ Clinically From Those Expected in the Normal Course of Progression of XLRS | Severe Ocular Inflammation (Day 8-Year 2) | 0 events |
| Cohort 5 | Adverse Events (AEs) Affecting Ocular Function That Differ Clinically From Those Expected in the Normal Course of Progression of XLRS | Substantial functional change (Day 0-Year 2) | 21 events |
| Cohort 5 | Adverse Events (AEs) Affecting Ocular Function That Differ Clinically From Those Expected in the Normal Course of Progression of XLRS | AEs Clinically Related to Intraocular Administration Technique (Day 8-Year 2) | 9 events |
| Cohort 5 | Adverse Events (AEs) Affecting Ocular Function That Differ Clinically From Those Expected in the Normal Course of Progression of XLRS | AEs affecting ocular function (differ clinically from expected in normal progression of XLRS) | 30 events |
| Cohort 5 | Adverse Events (AEs) Affecting Ocular Function That Differ Clinically From Those Expected in the Normal Course of Progression of XLRS | Decrease in Electroretinogram Response Amplitude (Day 0-Year 2) | 0 events |
Secondary
Change in Central Visual Field Sensitivity as Measured by Microperimetry (MP-1) Visual Field Testing
Change in central visual field sensitivity as measured by microperimetry (MP-1) Visual Field testing compared to average of baseline 1 and 2. Includes mean sensitivities, number of scotomatous points and number of points with a significant change in sensitivity.
Time frame: Baseline 1 through end of study participation (Year 5 or Year 7)
Population: Outcome was a secondary outcome. Images were not graded by a Reading Center and therefore data were not collected. Therefore these analyses were not performed.
Secondary
Change in Electroretinography Combined Response Amplitudes
Change in electroretinography combined response amplitudes from average of baseline 1 and 2 measurements. The higher the amplitude, the better.
Time frame: Baseline 1 through Year 2
Population: Includes all participants enrolled in the study and were administered the AAV vector injection, regardless of follow-up with data available for at least one baseline visit and at Year 2.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1 | Change in Electroretinography Combined Response Amplitudes | Dark-Adapted Combined Rod-Cone B-Wave 0dB Amplitude: Study Eye | -11.5 µV | Standard Deviation 24.5 |
| Cohort 1 | Change in Electroretinography Combined Response Amplitudes | Dark-Adapted Oscillatory Potentials Amplitude: Fellow Eye | -0.3 µV | Standard Deviation 3.8 |
| Cohort 1 | Change in Electroretinography Combined Response Amplitudes | Light-Adapted Cone A-Wave 11dB Amplitude: Fellow Eye | -6.8 µV | Standard Deviation 2.4 |
| Cohort 1 | Change in Electroretinography Combined Response Amplitudes | Dark-Adapted Rod Amplitude: Fellow Eye | -8.5 µV | Standard Deviation 25.5 |
| Cohort 1 | Change in Electroretinography Combined Response Amplitudes | Light-Adapted Flicker Amplitude: Fellow Eye | -0.2 µV | Standard Deviation 5.3 |
| Cohort 1 | Change in Electroretinography Combined Response Amplitudes | Light-Adapted Cone B-Wave 0dB Amplitude: Study Eye | -4.7 µV | Standard Deviation 6.3 |
| Cohort 1 | Change in Electroretinography Combined Response Amplitudes | Dark-Adapted Combined Rod-Cone A-Wave 11dB Amplitude: Fellow Eye | -36.8 µV | Standard Deviation 25 |
| Cohort 1 | Change in Electroretinography Combined Response Amplitudes | Light-Adapted Flicker Amplitude: Study Eye | -4.5 µV | Standard Deviation 11.5 |
| Cohort 1 | Change in Electroretinography Combined Response Amplitudes | Dark-Adapted Combined Rod-Cone A-Wave 0dB Amplitude: Fellow Eye | -20.8 µV | Standard Deviation 10.4 |
| Cohort 1 | Change in Electroretinography Combined Response Amplitudes | Dark-Adapted Combined Rod-Cone B-Wave 11dB Amplitude: Study Eye | -5.0 µV | Standard Deviation 34.2 |
| Cohort 1 | Change in Electroretinography Combined Response Amplitudes | Dark-Adapted Combined Rod-Cone A-Wave 11dB Amplitude: Study Eye | 1.3 µV | Standard Deviation 34.1 |
| Cohort 1 | Change in Electroretinography Combined Response Amplitudes | Dark-Adapted Combined Rod-Cone B-Wave 0dB Amplitude: Fellow Eye | -17.5 µV | Standard Deviation 31.4 |
| Cohort 1 | Change in Electroretinography Combined Response Amplitudes | Dark-Adapted Combined Rod-Cone A-Wave 0dB Amplitude: Study Eye | -0.5 µV | Standard Deviation 40.3 |
| Cohort 1 | Change in Electroretinography Combined Response Amplitudes | Dark-Adapted Rod Amplitude: Study Eye | 13.8 µV | Standard Deviation 19.3 |
| Cohort 1 | Change in Electroretinography Combined Response Amplitudes | Dark-Adapted Oscillatory Potentials Amplitude: Study Eye | -3.5 µV | Standard Deviation 2.2 |
| Cohort 1 | Change in Electroretinography Combined Response Amplitudes | Light-Adapted Cone A-Wave 11dB Amplitude: Study Eye | 1.8 µV | Standard Deviation 12.7 |
| Cohort 1 | Change in Electroretinography Combined Response Amplitudes | Light-Adapted Cone B-Wave 0dB Amplitude: Fellow Eye | -4.8 µV | Standard Deviation 6.7 |
| Cohort 1 | Change in Electroretinography Combined Response Amplitudes | Dark-Adapted Combined Rod-Cone B-Wave 11dB Amplitude: Fellow Eye | -17.5 µV | Standard Deviation 27.4 |
| Cohort 2 | Change in Electroretinography Combined Response Amplitudes | Dark-Adapted Combined Rod-Cone A-Wave 0dB Amplitude: Study Eye | -45.5 µV | Standard Deviation 19.5 |
| Cohort 2 | Change in Electroretinography Combined Response Amplitudes | Light-Adapted Cone B-Wave 0dB Amplitude: Fellow Eye | -4.2 µV | Standard Deviation 2.4 |
| Cohort 2 | Change in Electroretinography Combined Response Amplitudes | Dark-Adapted Combined Rod-Cone A-Wave 0dB Amplitude: Fellow Eye | -21.8 µV | Standard Deviation 19.5 |
| Cohort 2 | Change in Electroretinography Combined Response Amplitudes | Dark-Adapted Combined Rod-Cone A-Wave 11dB Amplitude: Study Eye | -29.5 µV | Standard Deviation 24.3 |
| Cohort 2 | Change in Electroretinography Combined Response Amplitudes | Dark-Adapted Oscillatory Potentials Amplitude: Fellow Eye | -6.8 µV | Standard Deviation 4.8 |
| Cohort 2 | Change in Electroretinography Combined Response Amplitudes | Dark-Adapted Combined Rod-Cone B-Wave 0dB Amplitude: Fellow Eye | -26.0 µV | Standard Deviation 21.8 |
| Cohort 2 | Change in Electroretinography Combined Response Amplitudes | Light-Adapted Cone A-Wave 11dB Amplitude: Study Eye | 1.5 µV | Standard Deviation 18.2 |
| Cohort 2 | Change in Electroretinography Combined Response Amplitudes | Light-Adapted Cone A-Wave 11dB Amplitude: Fellow Eye | -6.2 µV | Standard Deviation 3.8 |
| Cohort 2 | Change in Electroretinography Combined Response Amplitudes | Dark-Adapted Combined Rod-Cone B-Wave 11dB Amplitude: Fellow Eye | -18.8 µV | Standard Deviation 20.9 |
| Cohort 2 | Change in Electroretinography Combined Response Amplitudes | Light-Adapted Flicker Amplitude: Study Eye | -10.2 µV | Standard Deviation 16.8 |
| Cohort 2 | Change in Electroretinography Combined Response Amplitudes | Light-Adapted Cone B-Wave 0dB Amplitude: Study Eye | -4.8 µV | Standard Deviation 8 |
| Cohort 2 | Change in Electroretinography Combined Response Amplitudes | Light-Adapted Flicker Amplitude: Fellow Eye | -1.8 µV | Standard Deviation 11.5 |
| Cohort 2 | Change in Electroretinography Combined Response Amplitudes | Dark-Adapted Combined Rod-Cone B-Wave 0dB Amplitude: Study Eye | -44.8 µV | Standard Deviation 22 |
| Cohort 2 | Change in Electroretinography Combined Response Amplitudes | Dark-Adapted Combined Rod-Cone B-Wave 11dB Amplitude: Study Eye | -26.5 µV | Standard Deviation 24.9 |
| Cohort 2 | Change in Electroretinography Combined Response Amplitudes | Dark-Adapted Rod Amplitude: Study Eye | -21.7 µV | Standard Deviation 13.5 |
| Cohort 2 | Change in Electroretinography Combined Response Amplitudes | Dark-Adapted Oscillatory Potentials Amplitude: Study Eye | -12.2 µV | Standard Deviation 11.6 |
| Cohort 2 | Change in Electroretinography Combined Response Amplitudes | Dark-Adapted Combined Rod-Cone A-Wave 11dB Amplitude: Fellow Eye | -8.5 µV | Standard Deviation 8 |
| Cohort 2 | Change in Electroretinography Combined Response Amplitudes | Dark-Adapted Rod Amplitude: Fellow Eye | 14.0 µV | Standard Deviation 45.2 |
| Cohort 3 | Change in Electroretinography Combined Response Amplitudes | Dark-Adapted Oscillatory Potentials Amplitude: Study Eye | -4.7 µV | Standard Deviation 9.4 |
| Cohort 3 | Change in Electroretinography Combined Response Amplitudes | Light-Adapted Cone B-Wave 0dB Amplitude: Fellow Eye | 3.3 µV | Standard Deviation 25.9 |
| Cohort 3 | Change in Electroretinography Combined Response Amplitudes | Dark-Adapted Combined Rod-Cone A-Wave 0dB Amplitude: Study Eye | -21.7 µV | Standard Deviation 23 |
| Cohort 3 | Change in Electroretinography Combined Response Amplitudes | Dark-Adapted Combined Rod-Cone B-Wave 11dB Amplitude: Study Eye | -15.7 µV | Standard Deviation 16.5 |
| Cohort 3 | Change in Electroretinography Combined Response Amplitudes | Dark-Adapted Oscillatory Potentials Amplitude: Fellow Eye | -3.8 µV | Standard Deviation 9.5 |
| Cohort 3 | Change in Electroretinography Combined Response Amplitudes | Dark-Adapted Combined Rod-Cone A-Wave 11dB Amplitude: Fellow Eye | -3.2 µV | Standard Deviation 18 |
| Cohort 3 | Change in Electroretinography Combined Response Amplitudes | Light-Adapted Cone A-Wave 11dB Amplitude: Study Eye | -5.5 µV | Standard Deviation 13 |
| Cohort 3 | Change in Electroretinography Combined Response Amplitudes | Dark-Adapted Combined Rod-Cone B-Wave 0dB Amplitude: Fellow Eye | -6.8 µV | Standard Deviation 28.4 |
| Cohort 3 | Change in Electroretinography Combined Response Amplitudes | Dark-Adapted Rod Amplitude: Fellow Eye | -14.0 µV | Standard Deviation 38.5 |
| Cohort 3 | Change in Electroretinography Combined Response Amplitudes | Dark-Adapted Rod Amplitude: Study Eye | -13.8 µV | Standard Deviation 16.2 |
| Cohort 3 | Change in Electroretinography Combined Response Amplitudes | Dark-Adapted Combined Rod-Cone A-Wave 0dB Amplitude: Fellow Eye | -7.5 µV | Standard Deviation 6.8 |
| Cohort 3 | Change in Electroretinography Combined Response Amplitudes | Light-Adapted Flicker Amplitude: Study Eye | 1.2 µV | Standard Deviation 12.8 |
| Cohort 3 | Change in Electroretinography Combined Response Amplitudes | Light-Adapted Cone A-Wave 11dB Amplitude: Fellow Eye | -1.0 µV | Standard Deviation 14.1 |
| Cohort 3 | Change in Electroretinography Combined Response Amplitudes | Dark-Adapted Combined Rod-Cone A-Wave 11dB Amplitude: Study Eye | -30.7 µV | Standard Deviation 36.3 |
| Cohort 3 | Change in Electroretinography Combined Response Amplitudes | Light-Adapted Flicker Amplitude: Fellow Eye | 3.3 µV | Standard Deviation 22.4 |
| Cohort 3 | Change in Electroretinography Combined Response Amplitudes | Light-Adapted Cone B-Wave 0dB Amplitude: Study Eye | -2.0 µV | Standard Deviation 13.9 |
| Cohort 3 | Change in Electroretinography Combined Response Amplitudes | Dark-Adapted Combined Rod-Cone B-Wave 11dB Amplitude: Fellow Eye | -15.3 µV | Standard Deviation 11.1 |
| Cohort 3 | Change in Electroretinography Combined Response Amplitudes | Dark-Adapted Combined Rod-Cone B-Wave 0dB Amplitude: Study Eye | -9.5 µV | Standard Deviation 20 |
| Cohort 4 | Change in Electroretinography Combined Response Amplitudes | Dark-Adapted Combined Rod-Cone A-Wave 11dB Amplitude: Fellow Eye | -23.0 µV | — |
| Cohort 4 | Change in Electroretinography Combined Response Amplitudes | Dark-Adapted Oscillatory Potentials Amplitude: Fellow Eye | -9.0 µV | — |
| Cohort 4 | Change in Electroretinography Combined Response Amplitudes | Light-Adapted Cone B-Wave 0dB Amplitude: Study Eye | 12.5 µV | — |
| Cohort 4 | Change in Electroretinography Combined Response Amplitudes | Light-Adapted Cone B-Wave 0dB Amplitude: Fellow Eye | -5.5 µV | — |
| Cohort 4 | Change in Electroretinography Combined Response Amplitudes | Light-Adapted Cone A-Wave 11dB Amplitude: Study Eye | -10.5 µV | — |
| Cohort 4 | Change in Electroretinography Combined Response Amplitudes | Light-Adapted Cone A-Wave 11dB Amplitude: Fellow Eye | -7.0 µV | — |
| Cohort 4 | Change in Electroretinography Combined Response Amplitudes | Light-Adapted Flicker Amplitude: Study Eye | -24.0 µV | — |
| Cohort 4 | Change in Electroretinography Combined Response Amplitudes | Light-Adapted Flicker Amplitude: Fellow Eye | -22.0 µV | — |
| Cohort 4 | Change in Electroretinography Combined Response Amplitudes | Dark-Adapted Combined Rod-Cone B-Wave 11dB Amplitude: Study Eye | -8.0 µV | — |
| Cohort 4 | Change in Electroretinography Combined Response Amplitudes | Dark-Adapted Rod Amplitude: Study Eye | -19.0 µV | — |
| Cohort 4 | Change in Electroretinography Combined Response Amplitudes | Dark-Adapted Rod Amplitude: Fellow Eye | 4.5 µV | — |
| Cohort 4 | Change in Electroretinography Combined Response Amplitudes | Dark-Adapted Combined Rod-Cone A-Wave 0dB Amplitude: Study Eye | 15.5 µV | — |
| Cohort 4 | Change in Electroretinography Combined Response Amplitudes | Dark-Adapted Combined Rod-Cone A-Wave 0dB Amplitude: Fellow Eye | 4.5 µV | — |
| Cohort 4 | Change in Electroretinography Combined Response Amplitudes | Dark-Adapted Combined Rod-Cone B-Wave 0dB Amplitude: Study Eye | 23.0 µV | — |
| Cohort 4 | Change in Electroretinography Combined Response Amplitudes | Dark-Adapted Combined Rod-Cone B-Wave 0dB Amplitude: Fellow Eye | 14.0 µV | — |
| Cohort 4 | Change in Electroretinography Combined Response Amplitudes | Dark-Adapted Combined Rod-Cone A-Wave 11dB Amplitude: Study Eye | -36.5 µV | — |
| Cohort 4 | Change in Electroretinography Combined Response Amplitudes | Dark-Adapted Combined Rod-Cone B-Wave 11dB Amplitude: Fellow Eye | 10.0 µV | — |
| Cohort 4 | Change in Electroretinography Combined Response Amplitudes | Dark-Adapted Oscillatory Potentials Amplitude: Study Eye | -5.0 µV | — |
| Cohort 5 | Change in Electroretinography Combined Response Amplitudes | Dark-Adapted Combined Rod-Cone A-Wave 0dB Amplitude: Study Eye | -15.5 µV | — |
| Cohort 5 | Change in Electroretinography Combined Response Amplitudes | Dark-Adapted Oscillatory Potentials Amplitude: Fellow Eye | -10.5 µV | — |
| Cohort 5 | Change in Electroretinography Combined Response Amplitudes | Dark-Adapted Combined Rod-Cone A-Wave 11dB Amplitude: Study Eye | -4.5 µV | — |
| Cohort 5 | Change in Electroretinography Combined Response Amplitudes | Dark-Adapted Rod Amplitude: Fellow Eye | 14.5 µV | — |
| Cohort 5 | Change in Electroretinography Combined Response Amplitudes | Dark-Adapted Rod Amplitude: Study Eye | -11.0 µV | — |
| Cohort 5 | Change in Electroretinography Combined Response Amplitudes | Dark-Adapted Combined Rod-Cone B-Wave 11dB Amplitude: Study Eye | -35.0 µV | — |
| Cohort 5 | Change in Electroretinography Combined Response Amplitudes | Light-Adapted Flicker Amplitude: Fellow Eye | 2.5 µV | — |
| Cohort 5 | Change in Electroretinography Combined Response Amplitudes | Dark-Adapted Combined Rod-Cone A-Wave 11dB Amplitude: Fellow Eye | -12.5 µV | — |
| Cohort 5 | Change in Electroretinography Combined Response Amplitudes | Light-Adapted Flicker Amplitude: Study Eye | -20.0 µV | — |
| Cohort 5 | Change in Electroretinography Combined Response Amplitudes | Light-Adapted Cone A-Wave 11dB Amplitude: Fellow Eye | 7.0 µV | — |
| Cohort 5 | Change in Electroretinography Combined Response Amplitudes | Light-Adapted Cone A-Wave 11dB Amplitude: Study Eye | -2.5 µV | — |
| Cohort 5 | Change in Electroretinography Combined Response Amplitudes | Dark-Adapted Oscillatory Potentials Amplitude: Study Eye | -8.0 µV | — |
| Cohort 5 | Change in Electroretinography Combined Response Amplitudes | Dark-Adapted Combined Rod-Cone B-Wave 11dB Amplitude: Fellow Eye | -8.0 µV | — |
| Cohort 5 | Change in Electroretinography Combined Response Amplitudes | Light-Adapted Cone B-Wave 0dB Amplitude: Fellow Eye | 9.0 µV | — |
| Cohort 5 | Change in Electroretinography Combined Response Amplitudes | Light-Adapted Cone B-Wave 0dB Amplitude: Study Eye | -0.5 µV | — |
| Cohort 5 | Change in Electroretinography Combined Response Amplitudes | Dark-Adapted Combined Rod-Cone B-Wave 0dB Amplitude: Fellow Eye | -39.0 µV | — |
| Cohort 5 | Change in Electroretinography Combined Response Amplitudes | Dark-Adapted Combined Rod-Cone B-Wave 0dB Amplitude: Study Eye | -43.0 µV | — |
| Cohort 5 | Change in Electroretinography Combined Response Amplitudes | Dark-Adapted Combined Rod-Cone A-Wave 0dB Amplitude: Fellow Eye | -2.0 µV | — |
Secondary
Change in Retinal Structure as Measured by Optical Coherence Tomography
Change in retinal structure as measured by optical coherence tomography (OCT) compared to average of baseline 1 and 2. Includes a) quantitative measures of total retinal thickness obtained with the Cirrus OCT using macular cube scans, b) qualitative morphologic changes to macula anatomy investigated using the tracking ability of the Heidelberg Spectralis OCT system and c) length of intact ellipsoid zone on the OCT and any findings of restoration of this reflectivity line.
Time frame: Baseline 1 through end of study participation (Year 5 or Year 7)
Population: Outcome was a secondary outcome. Images were not graded by a Reading Center and therefore data were not collected. Therefore these analyses were not performed.
Secondary
Formation of Circulating Systemic Anti-AAV or Anti-RS1 Antibodies
Formation of circulating systemic anti-AAV or anti-RS1 antibodies assessed via serologic testing
Time frame: Day 0 through end of study participation (Year 5 or Year 7)
Population: Includes all participants enrolled in the study and were administered the AAV vector injection, regardless of follow-up.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1 | Formation of Circulating Systemic Anti-AAV or Anti-RS1 Antibodies | 0 events |
| Cohort 2 | Formation of Circulating Systemic Anti-AAV or Anti-RS1 Antibodies | 0 events |
| Cohort 3 | Formation of Circulating Systemic Anti-AAV or Anti-RS1 Antibodies | 0 events |
| Cohort 4 | Formation of Circulating Systemic Anti-AAV or Anti-RS1 Antibodies | 0 events |
| Cohort 5 | Formation of Circulating Systemic Anti-AAV or Anti-RS1 Antibodies | 0 events |
Secondary
Mean Change in Best Corrected Visual Acuity
Mean change in best corrected visual acuity (BCVA) at Year 2 compared to average of baseline 1 and 2. BCVA is measured via Electronic Visual Acuity (EVA).
Time frame: Baseline 1 through Year 2
Population: Includes all participants enrolled in the study and were administered the AAV vector injection, regardless of follow-up with data available for at least one baseline visit and at Year 2.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1 | Mean Change in Best Corrected Visual Acuity | Study Eye | 2.7 letters read | Standard Deviation 3.6 |
| Cohort 1 | Mean Change in Best Corrected Visual Acuity | Fellow Eye | -0.2 letters read | Standard Deviation 2.8 |
| Cohort 2 | Mean Change in Best Corrected Visual Acuity | Study Eye | -0.2 letters read | Standard Deviation 1.2 |
| Cohort 2 | Mean Change in Best Corrected Visual Acuity | Fellow Eye | 0.5 letters read | Standard Deviation 3.8 |
| Cohort 3 | Mean Change in Best Corrected Visual Acuity | Study Eye | -2.7 letters read | Standard Deviation 2.5 |
| Cohort 3 | Mean Change in Best Corrected Visual Acuity | Fellow Eye | -0.2 letters read | Standard Deviation 7.6 |
| Cohort 4 | Mean Change in Best Corrected Visual Acuity | Fellow Eye | -1.5 letters read | — |
| Cohort 4 | Mean Change in Best Corrected Visual Acuity | Study Eye | -1.0 letters read | — |
| Cohort 5 | Mean Change in Best Corrected Visual Acuity | Study Eye | -23.0 letters read | — |
| Cohort 5 | Mean Change in Best Corrected Visual Acuity | Fellow Eye | -26.0 letters read | — |
Secondary
Median and Distribution of Change in Best-Corrected Visual Acuity
Median and distribution of change in best-corrected visual acuity (BCVA) at Year 2 compared to average of baseline 1 and 2. BCVA is measured via Electronic Visual Acuity (EVA).
Time frame: Baseline 1 through Year 2
Population: Includes all participants enrolled in the study and were administered the AAV vector injection, regardless of follow-up with data available for at least one baseline visit and at Year 2.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Cohort 1 | Median and Distribution of Change in Best-Corrected Visual Acuity | Study Eye | 4.5 letters read |
| Cohort 1 | Median and Distribution of Change in Best-Corrected Visual Acuity | Fellow Eye | -1.0 letters read |
| Cohort 2 | Median and Distribution of Change in Best-Corrected Visual Acuity | Study Eye | 0.5 letters read |
| Cohort 2 | Median and Distribution of Change in Best-Corrected Visual Acuity | Fellow Eye | 1.0 letters read |
| Cohort 3 | Median and Distribution of Change in Best-Corrected Visual Acuity | Study Eye | -3.0 letters read |
| Cohort 3 | Median and Distribution of Change in Best-Corrected Visual Acuity | Fellow Eye | -1.5 letters read |
| Cohort 4 | Median and Distribution of Change in Best-Corrected Visual Acuity | Fellow Eye | -1.5 letters read |
| Cohort 4 | Median and Distribution of Change in Best-Corrected Visual Acuity | Study Eye | -1.0 letters read |
| Cohort 5 | Median and Distribution of Change in Best-Corrected Visual Acuity | Study Eye | -23.0 letters read |
| Cohort 5 | Median and Distribution of Change in Best-Corrected Visual Acuity | Fellow Eye | -26.0 letters read |