(086) Phase II Study of AbobotulinumtoxinA in Patients with Provoked Vestibulodynia: Outcomes From Dose-finding Stage

Abstract

Abstract Introduction Vulvodynia is associated with significant burden and impaired quality of life and affects up to 28% of women of reproductive age. The most common subtype is provoked vestibulodynia (PVD), in which pain is localized and triggered by vestibular contact. Treatment options are limited; no therapy is approved for PVD. Hypertonicity of the pelvic floor muscles is a common factor associated with PVD; therefore, patients may benefit from treatments that relax the pelvic floor. BotulinumtoxinA is used for prolonged muscle relaxation across multiple conditions. Current clinical data in patients with PVD are inconclusive, but off-label anecdotal use suggests benefit. Objective To assess the safety, efficacy, and optimal dosing of abobotulinumtoxinA (aboBoNT-A) for the treatment of PVD and explore the utility of a novel endpoint for pain assessment in PVD. Methods This phase II, randomized, placebo-controlled study (NCT03598777) comprised two steps: dose escalation (stage 1) and dose expansion (stage 2). Stage 1 included up to four treatment cycles; cycle 1 was double-blind, while cycles 2–4 were open-label. Patients were assessed for retreatment every 6 weeks. Enrolled premenopausal, adult women with PVD associated with pelvic-floor hypertonia were randomized 4:1 to receive aboBoNT-A (100 units [U] [n=8], 300 U [n=8], 400 U [n=14], and 500 U [n=17]) or placebo (n=13). A new efficacy endpoint was introduced, combining the use of eight vaginal dilators of increasing diameter and patient-reported pain in response to dilator insertion on an 11-point numeric rating scale (NRS) to derive a composite pain score. Based on the subjective pain threshold, the largest-sized dilator that the patient accepted was defined as the dilator maximum tested size (DMTS). Results Patients (aged 19–45 years; mean, 29.4 years) received aboBoNT-A or placebo. Baseline demographics and disease characteristics were well-balanced across treatment groups. All treatment-emergent adverse events (TEAEs) were mild or moderate. Among aboBoNT-A-treated patients, urinary incontinence occurred in one patient in cycle 1, one patient in cycle 2, and two patients in cycle 3. During cycle 1, treatment-related TEAEs occurred in patients receiving aboBoNT-A 500 U or placebo (3/17 patients and 1/13 patients, respectively), with none reported for doses <500 U. In terms of composite score for dilator test, there was a numerical trend for benefit with aboBoNT-A 300 U and a trend for increasing benefit with increasing number of injections. All women who received at least three active treatment cycles with aboBoNT-A had a decrease in dilator-induced pain from baseline of ≥30% and ≥2 points at week 6, as reported on the 11-point NRS. Efficacy and validity of the DMTS were not statistically analyzed owing to the sponsor’s decision to discontinue the trial (for reasons unrelated to efficacy or safety). Conclusions AboBoNT-A showed an acceptable safety profile in patients with PVD. Patients treated with multiple sequential cycles showed continued reductions in dilator-induced pain and NRS scores with repeated injections, suggesting a potential benefit of repeated aboBoNT-A treatment; trials assessing efficacy and validating DMTS are warranted to explore these findings. Disclosure Yes, this is sponsored by industry/sponsor: Ipsen Clarification: Industry initiated, executed and funded study Any of the authors act as a consultant, employee or shareholder of an industry for: Ipsen.