The purpose of the study was to assess safety and efficacy of autologous muscle derived cells for urinary sphincter repair (AMDC-USR) in female subjects with predominant stress urinary incontinence.
A randomized, double-blind, multicenter trial examined intra-sphincteric injection of 150 × 106 AMDC-USR versus placebo in female subjects with stress or stress predominant, mixed urinary incontinence. AMDC-USR products were generated from vastus lateralis needle biopsies. Subjects were randomized 2:1 to receive AMDC-USR or placebo and 1:1 to receive 1 or 2 treatments (6 months after the first). Primary outcome was composite of ≥ 50% reduction in stress incontinence episode frequency (IEF), 24-h or in-office pad weight tests at 12 months. Other outcome data included validated subject-recorded questionnaires. Subjects randomized to placebo could elect to receive open-label AMDC-USR treatment after 12 months. Subject follow-up was up to 2 years.
AMDC-USR was safe and well-tolerated with no product-related serious adverse events or discontinuations due to adverse events. Interim analysis revealed an unexpectedly high placebo response rate (90%) using the composite primary outcome which prevented assessment of treatment effect as designed and thus enrollment was halted at 61% of planned subjects. Post hoc analyses suggested that more stringent endpoints lowered placebo response rates and revealed a possible treatment effect.
Although the primary efficacy finding was inconclusive, these results inform future trial design of AMDC-USR to identify clinically meaningful efficacy endpoints based on IEF reduction, understanding of placebo response rate, and refinement of subject selection criteria to more appropriately align with AMDC-USR's proposed mechanism of action.
International urology and nephrology. 2018 Oct 15 [Epub ahead of print]
Ron J Jankowski, Le Mai Tu, Christopher Carlson, Magali Robert, Kevin Carlson, David Quinlan, Andreas Eisenhardt, Min Chen, Scott Snyder, Ryan Pruchnic, Michael Chancellor, Roger Dmochowski, Melissa R Kaufman, Lesley Carr
Cook MyoSite, Inc., 105 Delta Drive, 15238, Pittsburgh, PA, USA. ., Centre Hospitalier Universitaire de Sherbrooke, Sherbrooke, QC, Canada., Cook MyoSite, Inc., 105 Delta Drive, 15238, Pittsburgh, PA, USA., Foothills Medical Centre, Calgary, AB, Canada., Southern Alberta Institute of Urology, Calgary, AB, Canada., Victoria Gynecology and Continence Clinic, British Columbia, VIC, Canada., Praxisklinik Urologie Rhein-Ruhr, Mülheim, Germany., Cook Research Incorporated, West Layfette, IN, USA., Oakland University William Beaumont School of Medicine, Royal Oak, MI, USA., Vanderbilt University Medical Center, Nashville, TN, USA., Sunnybrook Health Sciences Centre, Toronto, ONT, Canada.