Abstract: PNFBA-03
Sources of Funding: Cook MyoSite, Incorporated

Introduction

This multicenter study (NCT01382602) assessed the safety and efficacy of Autologous Muscle Derived Cells for Urinary Sphincter Repair (AMDC-USR) in women with stress urinary incontinence (SUI).

Methods

Women with predominant SUI who experienced ≥3 stress leaks over 3 days were randomized 2:1 to receive intrasphincteric injection of 150 x 10⁶ AMDC-USR or vehicle placebo and 1:1 to receive 1 or 2 treatments. Second treatments were administered 6 months after first treatments. At baseline and follow-up, SUI was monitored by 3-day diaries of stress incontinence episode frequency (IEF), 24-hour pad tests, in-office pad tests, and quality of life (QOL) questionnaires. The primary composite efficacy endpoint was the percentage of patients with ≥50% IEF reduction or ≥50% reduction in either pad test 12 months post-treatment. Patients were unblinded after completing 12-month visits, and patients who received placebo could opt to receive an open-label AMDC-USR treatment. Patients were followed for 2 years after initial treatment.

Results

Overall, 143 patients were treated (50 placebo; 93 AMDC-USR), 141 patients completed 12-month visits (50 placebo, 91 AMDC-USR), 127 patients completed 2-year visits, and 3 patients remain in follow-up. Both placebo and AMDC-USR groups had similar baseline characteristics. No AMDC-USR safety signals were identified and no urinary retention was reported. Due to an unexpectedly high placebo responder rate with the composite endpoint, which included pad tests, enrollment was halted at 61% (150/246) of the planned study size. In post hoc analyses, IEF reduction correlated with QOL score improvement and suggested that ≥50% IEF reduction, ≥75% IEF reduction, and ≤1 leak per 3 days may be clinically meaningful endpoints. With these alternate endpoints, placebo rates were reduced and a potential treatment effect was detected (Figure). Further, 84% (37/44) of AMDC-USR patients with ≥50% IEF reduction at 12 months and available 2-year diaries also met this endpoint at 2 years. At final follow-up, 56% (20/36) of patients who received open-label AMDC-USR and had ≥3 stress leaks at 12 months had ≥50% IEF reduction compared to the 12-month diary collected before unblinding.

Conclusions

In women with SUI, AMDC-USR is safe and may provide durable reduction in IEF.

Funding

Cook MyoSite, Incorporated