The purpose of this study is to evaluate the safety and tolerability of QR-421a administered via intravitreal injection (IVT) in subjects with Retinitis Pigmentosa (RP) due to mutations in exon 13 of the USH2A gene.
The purpose of this study is to evaluate the safety and tolerability of QR-421a administered via IVT in subjects with RP due to mutations in exon 13 of the USH2A gene. Subjects will receive one single IVT injection of QR-421a or sham-procedure in one eye (subject's worse eye) and will be followed up for 24 months. Three dose levels of QR-421a will be evaluated: 50, 100, and 200 µg. Additional dose levels (eg, 25 or 400 µg) may be evaluated based on ongoing safety and efficacy data monitoring. Initial dose cohorts will include subjects randomized to sham-procedure or treatment with QR-421a. Additional subjects may be allocated to treatment with QR-421a in subsequent or initial dose cohorts.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
20
RNA antisense oligonucleotide for intravitreal injection
Sham-procedure (no experimental drug administered)
Center for Clinical Research Operations, Massachusetts Eye and Ear
Boston, Massachusetts, United States
University of Michigan, Kellogg Eye Center
Ann Arbor, Michigan, United States
Casey Eye Institute, Oregon Health & Science University
Portland, Oregon, United States
Retina Foundation of the Southwest
Dallas, Texas, United States
Centre for Innovative Medicine, Department of Paediatric Surgery, Montreal Children's Hospital at the McGill University Health Centre
Montreal, Canada
Hôpital Gui de Chauliac - CHRU de Montpellier - Maladies Sensorielles Génétique
Montpellier, France
Centre de maladies rares CHNO des Quinze Vingts
Paris, France
Incidence and severity of ocular adverse events (AEs) in the treatment and contralateral eye
Incidence and severity of ocular AEs
Time frame: 24 months
Incidence and severity of non-ocular AEs
Incidence and severity of non-ocular AEs
Time frame: 24 months
Change in DAC perimetry
Change in Dark Adapted Chromatic (DAC) perimetry
Time frame: 24 months
Change in static perimetry
Change in static perimetry
Time frame: 24 months
Change in EZ area by SD-OCT
Change in Ellipsoid Zone (EZ) area/width by spectral domain optical coherence tomography (SD-OCT)
Time frame: 24 months
Change in BCVA
Change in Best Corrected Visual Acuity (BCVA)
Time frame: 24 months
Change in LLVA
Change in Low Luminance Visual Acuity (LLVA)
Time frame: 24 months
Change in microperimetry
Change in microperimetry
Time frame: 24 months
Changes in FST
Changes in Full-field Stimulus Threshold (FST)
Time frame: 24 months
Changes in FAF
Changes in Fundus autofluorescence (FAF)
Time frame: 24 months
AUC (0-∞) of QR-421a in serum
Area under the curve 0 hour to infinity \[AUC(0-∞)\] of QR-421a in serum
Time frame: 24 months
AUC (0-tlast) of QR-421a in serum
Area under the curve 0 hour to the final sample with a concentration greater than lower limit of quantification (LLOQ) \[AUC(0-tlast)\] of QR-421a in serum
Time frame: 24 months
Cmax of QR-421a in serum
Maximum concentration (Cmax) of QR-421a in serum
Time frame: 24 months
Tmax of QR-421a
Time to maximum concentration (Tmax) of QR-421a
Time frame: 24 months
T1/2 of QR-421a
Terminal elimination half-life (T1/2) of QR-421a
Time frame: 24 months
Serum clearance (CL) of QR-421a
Serum clearance (CL) of QR-421a
Time frame: 24 months
Volume of distribution (Vd) of QR-421a
Volume of distribution (Vd) of QR-421a
Time frame: 24 months
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