Leber's Congenital Amaurosis
Conditions
Keywords
CEP290, p.Cys998X, c.2991+1655A>G, RNA therapy, Antisense oligonucleotide, Leber's congenital amaurosis
Brief summary
The purpose of this study is to evaluate the safety and tolerability of QR-110 administered via intravitreal injection in subjects with LCA due to the CEP290 p.Cys998X mutation.
Detailed description
The purpose of this study is to evaluate the safety and tolerability of QR-110 administered via intravitreal injection in subjects with LCA due to the CEP290 p.Cys998X mutation. Subjects will receive QR-110 in one eye every 3 months, for a maximum of 4 doses. Up to 3 dose levels of QR-110 will be evaluated.
Interventions
DRUGQR-110
RNA antisense oligonucleotide for intravitreal injection
Sponsors
Sepul Bio
Laboratoires Thea
Study design
Allocation
NA
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
6 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Male or female, ≥ 6 years of age at Screening with a clinical diagnosis of LCA and a molecular diagnosis of homozygosity or compound heterozygosity for the CEP290 p.Cys998X mutation. * Best-corrected visual acuity greater than or equal to light perception in both eyes and equal to or worse than LogMAR +1.0 (Snellen notation 20/200) in the worse eye and equal to or worse than LogMAR +0.7 (Snellen notation 20/100) in the contralateral eye. * Detectable outer nuclear layer (ONL) in the area of the macula. * An electroretinogram (ERG) result consistent with LCA. * Clear ocular media and adequate pupillary dilation to permit good quality retinal imaging.
Exclusion criteria
* Syndromic disease. * Pregnant or breast-feeding female. * Any clinically significant cardiac disease or defect. * One or more coagulation parameters outside of the normal range. * Any ocular disease or condition that could compromise treatment safety, visual acuity or interfere with assessment of efficacy and safety. * Prior receipt of intraocular surgery or intravitreal injection within 3 months prior to study start or planned intraocular surgery or procedure during the course of the study. * Use of any investigational drug or device within 90 days or 5 half-lives of Day 1, whichever is longer, or plans to participate in another study of a drug or device during the PQ-110-001 study period. * Any prior receipt of genetic therapy for LCA
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Frequency and Severity of Ocular Adverse Events in the Treatment and Contralateral Eyes | 1 year |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Frequency and Severity of Non-ocular Adverse Events | 1 year | — |
| Change in Best-corrected Visual Acuity (BCVA) | 1 year | — |
| Change in Full-field Stimulus Test (FST) | 1 year | Average Red Light Score |
Countries
Belgium, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| QR-110 Low Dose 160/80 μg Cohort | 6 |
| QR-110 Mid Dose 320/160 μg Cohort | 5 |
| Total | 11 |
Baseline characteristics
| Characteristic | QR-110 Low Dose | QR-110 Mid Dose | Total |
|---|---|---|---|
| Age, Continuous | 23.7 years STANDARD_DEVIATION 15.06 | 19.4 years STANDARD_DEVIATION 6.88 | 21.7 years STANDARD_DEVIATION 11.71 |
| Age, Customized 18 to < 65 years | 3 Participants | 3 Participants | 6 Participants |
| Age, Customized 6 to < 18 years | 3 Participants | 2 Participants | 5 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 6 Participants | 5 Participants | 11 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 6 Participants | 5 Participants | 11 Participants |
| Sex: Female, Male Female | 2 Participants | 4 Participants | 6 Participants |
| Sex: Female, Male Male | 4 Participants | 1 Participants | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 6 | 0 / 5 |
| other Total, other adverse events | 6 / 6 | 5 / 5 |
| serious Total, serious adverse events | 2 / 6 | 4 / 5 |
Outcome results
Primary
Frequency and Severity of Ocular Adverse Events in the Treatment and Contralateral Eyes
Time frame: 1 year
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| QR-110 Low Dose | Frequency and Severity of Ocular Adverse Events in the Treatment and Contralateral Eyes | 6 Participants |
| QR-110 Mid Dose | Frequency and Severity of Ocular Adverse Events in the Treatment and Contralateral Eyes | 5 Participants |
Secondary
Change in Best-corrected Visual Acuity (BCVA)
Time frame: 1 year
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| QR-110 Low Dose | Change in Best-corrected Visual Acuity (BCVA) | Changes from Baseline - Visit 17 (M9) | -0.923 logMAR | Standard Deviation 1.0417 |
| QR-110 Low Dose | Change in Best-corrected Visual Acuity (BCVA) | Changes from Baseline - Visit 21 (M12) | -0.927 logMAR | Standard Deviation 1.0492 |
| QR-110 Low Dose | Change in Best-corrected Visual Acuity (BCVA) | Baseline (Absolute Values) | 2.597 logMAR | Standard Deviation 1.2738 |
| QR-110 Low Dose | Change in Best-corrected Visual Acuity (BCVA) | Changes from Baseline - Visit 8 (M3) | -0.813 logMAR | Standard Deviation 1.0073 |
| QR-110 Low Dose | Change in Best-corrected Visual Acuity (BCVA) | Changes from Baseline - Visit 13 (M6) | -0.903 logMAR | Standard Deviation 1.0189 |
| QR-110 Mid Dose | Change in Best-corrected Visual Acuity (BCVA) | Changes from Baseline - Visit 13 (M6) | -0.122 logMAR | Standard Deviation 0.1801 |
| QR-110 Mid Dose | Change in Best-corrected Visual Acuity (BCVA) | Changes from Baseline - Visit 17 (M9) | 0.386 logMAR | Standard Deviation 0.961 |
| QR-110 Mid Dose | Change in Best-corrected Visual Acuity (BCVA) | Changes from Baseline - Visit 8 (M3) | -0.126 logMAR | Standard Deviation 0.2165 |
| QR-110 Mid Dose | Change in Best-corrected Visual Acuity (BCVA) | Changes from Baseline - Visit 21 (M12) | -0.106 logMAR | Standard Deviation 0.1545 |
| QR-110 Mid Dose | Change in Best-corrected Visual Acuity (BCVA) | Baseline (Absolute Values) | 2.990 logMAR | Standard Deviation 1.4153 |
Secondary
Change in Full-field Stimulus Test (FST)
Average Red Light Score
Time frame: 1 year
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| QR-110 Low Dose | Change in Full-field Stimulus Test (FST) | -0.7 log cd/m2 | Standard Deviation 0.33 |
| QR-110 Mid Dose | Change in Full-field Stimulus Test (FST) | -1.2 log cd/m2 | Standard Deviation 0.82 |
Secondary
Change in Full-field Stimulus Test (FST)
Average Blue Light Score
Time frame: 1 year
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| QR-110 Low Dose | Change in Full-field Stimulus Test (FST) | -0.6 log cd/m2 | Standard Deviation 0.76 |
| QR-110 Mid Dose | Change in Full-field Stimulus Test (FST) | -0.9 log cd/m2 | Standard Deviation 0.82 |
Secondary
Frequency and Severity of Non-ocular Adverse Events
Time frame: 1 year
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| QR-110 Low Dose | Frequency and Severity of Non-ocular Adverse Events | 6 Participants |
| QR-110 Mid Dose | Frequency and Severity of Non-ocular Adverse Events | 5 Participants |