Abstract
Purpose: A phase 1 single ascending dose first-in-human study was conducted to evaluate the safety and tolerability of VP-001, an antisense oligonucleotide designed to reduce CNOT3 expression thus allowing upregulation of PRPF31.
Methods: Twelve participants with PRPF31-associated rod-cone dystrophy (RP11) were recruited in four cohorts. One eye of each participant received an intravitreal injection of VP-001 (3, 10, 30, and 75 μg) and followed for 48 weeks for adverse events. Dose escalation was determined by a safety review committee. Visual acuity, slit lamp examination, microperimetry, fundus autofluorescence imaging, optical coherence tomography, full-field sensitivity threshold and clinical chemistry parameters were collected.
Results: No significant drug-related adverse events or intraocular inflammation were observed during the 12-week follow-up period for the 30 μg cohort, and for at least 24 weeks in the 3 and 10 μg cohorts. Results for the fourth cohort receiving a 75 μg dose will be presented. One subject who received a 30 μg dose demonstrated >7 dB retinal sensitivity improvement in 6 of the 10-2 microperimetry grid loci in the treated eye compared to only one locus in the untreated fellow eye at eight weeks post-dosing, and the effect in the treated eye persisted for 15 weeks. OCT showed no significant change in central subfield thickness.
Conclusions: A single intravitreal injection of VP-001 was safe and well tolerated at 3, 10 and 30 μg doses. One case demonstrated significant retinal sensitivity improvement. Longer-term data from all four cohorts will be presented.