AURORA: A Study to Evaluate the Safety and Tolerability of QR-1123 in Subjects With Autosomal Dominant Retinitis Pigmentosa Due to the P23H Mutation in the RHO Gene
Study Details
Study Description
Brief Summary
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.
Condition or Disease | Intervention/Treatment | Phase |
---|---|---|
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Phase 1/Phase 2 |
Detailed Description
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.
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
---|---|
Experimental: QR-1123 Single dose - dose level 1 Open label Single dose cohort: dose level 1 |
Drug: QR-1123
unilateral IVT injection
|
Experimental: QR-1123 Single dose - dose level 2 Open label Single dose cohort: dose level |
Drug: QR-1123
unilateral IVT injection
|
Experimental: QR-1123 Single dose - dose level 3 Open label Single dose cohort: dose level 3 |
Drug: QR-1123
unilateral IVT injection
|
Experimental: QR-1123 Single dose - dose level 4 Open label Single dose cohort: dose level 4 |
Drug: QR-1123
unilateral IVT injection
|
Experimental: QR-1123 Single dose - dose level 5 Open label Single dose cohort: dose level 5 |
Drug: QR-1123
unilateral IVT injection
|
Experimental: Repeat dose cohort 1 Double-masked, randomized, sham controlled, Repeat dose cohort. Dose levels will be determined following DMC review of obtained safety and efficacy data. |
Drug: QR-1123
unilateral IVT injection
Other: Sham procedure
Sham procedures (i.e. no penetration of the globe) closely mimic the active injection and serve to mask subjects to treatment assignment
|
Outcome Measures
Primary Outcome Measures
- Incidence and Severity of ocular AEs [up to 12 months]
Incidence and severity of ocular adverse events scored based on CTCAC in the study and fellow eye
- Incidence and Severity of non-ocular AEs [up to 12 months]
Incidence and severity of non-ocular adverse events scored based on CTCAC in the study and fellow eye
Secondary Outcome Measures
- Changes in BCVA [up to 12 months]
Changes in Best corrected visual acuity (BCVA)
- Changes in LLVA [up to 12 months]
Changes in Low-luminance visual acuity (LLVA)
- Changes in DAC perimetry [up to 12 months]
Changes in Dark adapted chromatic (DAC) perimetry
- Changes in Static VF [up to 12 months]
Changes in Static VF (Visual Field)
- Changes in Microperimetry [up to 12 months]
Changes in Microperimetry
- Changes in SD-OCT [up to 12 months]
Changes in Spectral Domain-Optical Coherence Tomography
- Changes in FST [up to 12 months]
Changes in Full-field Stimulus Threshold (FST)
- Changes in Full-field ERG [up to 12 months]
Changes in Full-field Electroretinogram (ERG)
- Assessment of systemic exposure after treatment with QR-1123 [up to 12 months]
Serum levels of QR-1123
Eligibility Criteria
Criteria
Main Inclusion Criteria:
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Male or female, ≥ 18 years of age.
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Clinical presentation consistent with adRP, based on ophthalmic examinations.
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Impairment on VF in the opinion of the Investigator, as determined by perimetry.
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A molecular diagnosis of autosomal dominant form of RP with the P23H mutation in the RHO gene, based on genetic analysis.
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A clear ocular media and adequate pupillary dilation to permit good quality fundus imaging, as assessed by the Investigator.
Main Exclusion Criteria:
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Presence of additional pathogenic mutations in genes (other than the P23H mutation in the RHO gene) associated with inherited retinal degenerative diseases or syndromes, based on genetic analysis (eg, Usher syndrome, Leber congenital amaurosis, etc).
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Presence of any significant ocular or non-ocular disease/disorder (including medication and laboratory test abnormalities) which, in the opinion of the Investigator and with concurrence of the Medical Monitor, may either put the subject at risk because of participation in the study, may influence the results of the study, or the subject's ability to participate in the study.
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
---|---|---|---|---|---|
1 | Sue Anschutz-Rogers Eye Center, University of Colorado - Dept. of Ophthalmology | Aurora | Colorado | United States | 80045 |
2 | VitreoRetinal Associates | Gainesville | Florida | United States | 32607 |
3 | Shriners UK Ophthalmology - University of Kentucky | Lexington | Kentucky | United States | 40536 |
4 | Casey Eye Institute, OHSU | Portland | Oregon | United States | 97239 |
5 | Retina Foundation of the Southwest | Dallas | Texas | United States | 75231 |
Sponsors and Collaborators
- ProQR Therapeutics
Investigators
- Study Director: ProQR Medical Monitor, ProQR Therapeutics
- Study Director: ProQR Clinical Trial Manager, ProQR Therapeutics
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- PQ-1123-001