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    SUI: Phase III data offer lessons for trials evaluating cell therapy

    Results of one of the first randomized controlled trials evaluating cell therapy for women with stress urinary incontinence (SUI) has helped to identify clinically meaningful efficacy endpoints to refine patient selection criteria for current and future studies, according to investigator Melissa R. Kaufman, MD, PhD.

    The phase III findings, described in a presentation at the International Continence Society annual meeting in Florence, Italy, involve the use of autologous muscle-derived cells (AMDCs) that are administered as an intrasphincteric injection designed to augment sphincter function.

    The randomized trial had a composite endpoint of ≥50% reduction in incontinence episode frequency (IEF) or ≥50% reduction in either 24-hour or in-office pad tests 12 months post-treatment. When investigators found that response rates for this endpoint exceeded 80% for both treatment and placebo arms, they halted the trial after 150 of a planned 246 women had been enrolled.

    Now underway is a phase III trial that will look at IEF reduction endpoints that are more clinically meaningful, according to Dr. Kaufman, of Vanderbilt University Medical Center, Nashville, TN.

    “The primary lesson is that complex clinical trials are an iterative process,” Dr. Kaufman said in an interview with Urology Times. “We must remain open to understanding the nuances of our design when embarking on trials for novel technologies, especially when data is not historically available to benchmark.”

    The AMDCs under study are developed from muscle tissue obtained from the patient. After enzymatic and mechanical disruption, muscle cells are serially plated until adult cells exhibiting qualities believed to lead to regenerative potential are purified and expanded in quantity, according to Dr. Kaufman. After testing for safety, muscle-cell identity, and potency, the cells are packaged and returned to the clinical site for injection.

    Previously published phase I/II data suggest that using AMDCs for urinary sphincter repair is safe, with adverse events that are transient, self-limited, and attributable to biopsy or injection, rather than the cells themselves (J Urol 2014; 192:469-75). Efficacy data, while early and preliminary, included a statistically significant improvement in patient-reported outcome scores at 12-month follow-up compared to baseline.

    This information drove construction of the current phase III trial design, which included the composite endpoint that proved to provide “excessive inclusivity and resulted in capture of many placebo patients,” said Dr. Kaufman, who added that unreliability of pad testing in this population further confounded the results.

    Next: Identifying alternate endpoints

    Andrew Bowser
    Andrew Bowser is a medical writer based in Brooklyn, New York.

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