A Double-Blind, Randomized, Controlled Trial Comparing Safety and Efficacy of Autologous Muscle Derived Cells For Urinary Sphincter Repair (AMDC-USR) With Placebo (PBO) in Women With Stress Urinary Incontinence (SUI)
Journal of Urology
INTRODUCTION AND OBJECTIVE:
This multicenter Phase 3 study (NCT01893138) evaluated efficacy and safety of AMDC-USR compared to PBO for SUI treatment. METHODS:
297 adult women with average 14.4 ± 11.4 stress leaks over 3 days were randomized 2:1 (150x106 AMDC-USR:vehicle PBO) and stratified by baseline severity and prior SUI surgery. AMDC-USR was manufactured from vastus lateralis harvest via outpatient biopsy and injected into the urinary sphincter at a subsequent outpatient procedure. SUI was monitored by 3-day diary of stress incontinence episode frequency (SIEF) and quality of life (QOL) questionnaires. Subjects were unblinded after 12 months, and PBO subjects could receive an open-label AMDC-USR treatment. Subjects were followed for 2 years post initial treatment. RESULTS:
297 women were treated (199 AMDC-USR; 98 PBO), 99% completed 12 months (199 AMDC-USR; 96 PBO), and 85% have completed 2 years (167 AMDC-USR; 86 PBO). 93% PBO subjects opted to receive open-label AMDC-USR treatment. Percentage of SIEF responders by strata, endpoints and visits is presented below. SIEF reduction correlated with improvement in all QOL scores at 12 months (p < 0.001). Treatment-related serious adverse reactions were uncommon (< 1%) with no AMDC-USR safety signals detected.
Single injection of AMDC-USR is safe and durable through 2 years with varying therapeutic effect. Consistent with our previous study, ≥ 50% SIEF reduction is not a sufficient endpoint. High variability in PBO response rates across strata impacts generalizability of the treatment response in the overall population. Nonetheless, there was encouraging response in subjects with > 10 baseline SIE, and a markedly greater percentage (> 2-fold) of women with prior surgery achieved statistical and clinically meaningful ≥ 75% SIEF reduction compared with PBO, further supporting that this population may be ideally suited for AMDC-USR therapy.
Kaufman MR, Peters KM, Chermansky CJ, Quiroz LH, Bennett JB, Thomas S, et al. A Double-blind, randomized, controlled trial comparing safety and efficacy of autologous muscle derived cells for urinary sphincter repair (AMDC-USR) with placebo (PBO) in women with stress urinary incontinence (SUI). J Urol. 2021 Sep;206(suppl 3):e99.