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This study evaluates the safety, tolerability and efficacy of QR-1123 injection in the eye (intravitreal; IVT) injections (one eye/unilateral) in subjects receiving a single dose or repeat doses. Single injections will be assessed in an open label way, and repeat injections will be assessed in a double-masked, randomized, sham-controlled fashion.
QR-1123 is an antisense oligonucleotide, designed to specifically target the mutant P23H messenger ribonucleic acid (mRNA) in order to reduce the expression of the P23H protein selectively, while preserving expression of the wild type (WT) rhodopsin (RHO) protein. It is hypothesized that the reduction of mutant P23H mRNA will reduce the deleterious effects of the dominant-negative protein and should result in increased function of WT rhodopsin protein in photoreceptors. Restoration of WT RHO function is expected to improve vision in patients with adRP due to the P23H mutation.
The study will comprise up to 8 single dose and repeat dose cohorts. Prior to initiating a higher single dose cohort and/or prior to initiating repeat dose cohort(s), available safety and efficacy data will be reviewed by the DMC.
In the single dose cohorts subjects will receive a single, unilateral IVT injection of QR-1123 in an open label fashion. In the repeat dose cohorts subjects will be randomized to receive either a unilateral IVT injection of QR-1123 every 3 months or a unilateral sham procedure every 3 months, in a double masked fashion. Subjects will be followed for safety, tolerability and efficacy for a total period of 12 months.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| QR-1123 Single dose - dose level 1 | Experimental | Open label Single dose cohort: dose level 1 |
|
| QR-1123 Single dose - dose level 2 | Experimental | Open label Single dose cohort: dose level |
|
| QR-1123 Single dose - dose level 3 | Experimental | Open label Single dose cohort: dose level 3 |
|
| QR-1123 Single dose - dose level 4 | Experimental | Open label Single dose cohort: dose level 4 |
|
| QR-1123 Single dose - dose level 5 | Experimental | Open label Single dose cohort: dose level 5 |
|
| Repeat dose cohort 1 | Experimental | Double-masked, randomized, sham controlled, Repeat dose cohort. Dose levels will be determined following DMC review of obtained safety and efficacy data. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| QR-1123 | Drug | unilateral IVT injection |
|
| Measure | Description | Time Frame |
|---|---|---|
| Incidence and Severity of ocular AEs | Incidence and severity of ocular adverse events scored based on CTCAC in the study and fellow eye | up to 12 months |
| Incidence and Severity of non-ocular AEs | Incidence and severity of non-ocular adverse events scored based on CTCAC in the study and fellow eye | up to 12 months |
| Measure | Description | Time Frame |
|---|---|---|
| Changes in BCVA | Changes in Best corrected visual acuity (BCVA) | up to 12 months |
| Changes in LLVA | Changes in Low-luminance visual acuity (LLVA) |
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Main Inclusion Criteria:
Main Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| ProQR Medical Monitor | ProQR Therapeutics | Study Director |
| ProQR Clinical Trial Manager | ProQR Therapeutics | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Sue Anschutz-Rogers Eye Center, University of Colorado - Dept. of Ophthalmology | Aurora | Colorado | 80045 | United States | ||
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Single dose cohorts are open label. Repeat dose cohorts are randomized, double masked.
|
| Sham procedure | Other | Sham procedures (i.e. no penetration of the globe) closely mimic the active injection and serve to mask subjects to treatment assignment |
|
| up to 12 months |
| Changes in DAC perimetry | Changes in Dark adapted chromatic (DAC) perimetry | up to 12 months |
| Changes in Static VF | Changes in Static VF (Visual Field) | up to 12 months |
| Changes in Microperimetry | Changes in Microperimetry | up to 12 months |
| Changes in SD-OCT | Changes in Spectral Domain-Optical Coherence Tomography | up to 12 months |
| Changes in FST | Changes in Full-field Stimulus Threshold (FST) | up to 12 months |
| Changes in Full-field ERG | Changes in Full-field Electroretinogram (ERG) | up to 12 months |
| Assessment of systemic exposure after treatment with QR-1123 | Serum levels of QR-1123 | up to 12 months |
| VitreoRetinal Associates |
| Gainesville |
| Florida |
| 32607 |
| United States |
| Shriners UK Ophthalmology - University of Kentucky | Lexington | Kentucky | 40536 | United States |
| Casey Eye Institute, OHSU | Portland | Oregon | 97239 | United States |
| Retina Foundation of the Southwest | Dallas | Texas | 75231 | United States |
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| Release Date | Unrelease Date | Unrelease Date Unknown | Reset Date | MCP Release Number |
|---|---|---|---|---|
| Nov 11, 2022 | Dec 6, 2022 | 11 | ||
| Dec 9, 2022 | Jan 3, 2023 | 12 |
| ID | Term |
|---|---|
| D005128 | Eye Diseases |
| D015785 | Eye Diseases, Hereditary |
| D058499 | Retinal Dystrophies |
| D012164 | Retinal Diseases |
| D012173 | Retinitis |
| D014786 | Vision Disorders |
| D012174 | Retinitis Pigmentosa |
| C566474 | Night Blindness, Congenital Stationary, Autosomal Dominant 1 |
| C566739 | Multiple Pterygium Syndrome, Autosomal Dominant |
| ID | Term |
|---|---|
| D030342 | Genetic Diseases, Inborn |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D012162 | Retinal Degeneration |
| D012678 | Sensation Disorders |
| D009461 | Neurologic Manifestations |
| D009422 | Nervous System Diseases |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
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