Impact of Condoliase on Health-related Quality of Life in Participants with Radicular Leg Pain Associated with Lumbar Disk Herniation: Results from a United States Phase 3 Clinical Trial

Abstract

Study Design. An exploratory analysis of a randomized, double-blind, sham-controlled, phase three study. Objective. To evaluate the impact of SI-6603 (condoliase) on health-related quality of life (HRQoL)-related outcomes in patients with lumbar disk herniation (LDH)-associated radicular leg pain from the Discovery 6603 study (NCT03607838). Summary of Background Data. Condoliase is a novel chemonucleolytic agent that selectively degrades chondroitin sulfate in the nucleus pulposus. Condoliase is approved in Japan for the treatment of radicular leg pain associated with LDH. Recently, the Discovery 6603 study demonstrated the efficacy and tolerability of condoliase in the United States (US). Methods. Adults with LDH and unilateral radicular leg pain were randomized to receive a single intradiscal injection of condoliase (1.25 units) or sham, followed by 52 weeks of observation. Exploratory HRQoL-related outcomes included change from baseline (CFB) in EuroQol Group 5-Dimension Quality of Life instrument, 5-Level version (EQ-5D-5L), and visual analogue scale (EQ-VAS), CFB in the 36-item Short Form Health Survey (SF-36), Patient Global Impression of Change (PGIC), Clinical Global Impression of Change (CGIC), and CFB in Work Productivity and Activity Impairment (WPAI) scores. EQ-5D-5L and SF-36 measures were assessed using a longitudinal analysis model. Results. Of 352 randomized participants, 341 constituted the modified intention-to-treat population (condoliase: 169; sham: 172). Condoliase showed numerically greater improvements in EQ-5D-5L self-care and pain/discomfort dimensions at week 13 and week 52 compared with sham (P<0.05). The SF-36 physical component and WPAI scores numerically favored condoliase compared with sham. Patients and clinicians more frequently reported "very much improved"in overall status following condoliase treatment versus sham. Conclusions. Previous findings confirmed the efficacy and tolerability of condoliase for LDH management. Condoliase showed notable improvements in exploratory HRQoL-related outcomes, which were consistent across multiple patient-reported measures. Condoliase has the potential to enhance QoL and work productivity in individuals with LDH.