Phase 2 randomized study of abobotulinumtoxinA in patients with provoked vestibulodynia: dose-finding results.

[BACKGROUND] Hypertonicity of the pelvic floor muscles is commonly associated with provoked vestibulodynia (PVD); therefore, patients may benefit from treatments that relax the pelvic floor.

[AIM] To define optimal (safe and efficacious) doses of abobotulinumtoxinA (aboBoNT-A) for the treatment of PVD associated with hypertonic pelvic floor muscle dysfunction and to explore use of a novel endpoint for pain assessment for PVD.

[METHODS] This phase 2, randomized, placebo-controlled study 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, Cycles 2-4 open label. Patients were assessed for retreatment every 6 weeks. Stage 2 was not conducted because of early study termination by the sponsor, unrelated to observed safety signals. Enrolled patients-premenopausal women with PVD with associated pelvic-floor hypertonia-were randomized (n = 60) 4:1 to receive aboBoNT-A (doses: 100, 300, 400, or 500 units [U]) or placebo.

[OUTCOMES] The primary endpoint was safety. Additionally, a novel composite endpoint, dilator maximum tested size was evaluated. This endpoint combined assessment of vaginal-dilator tolerability with patient-reported pain assessment on an 11-point numeric rating scale, used as a surrogate measure of sexual activity in this study.

[RESULTS] All treatment-emergent adverse events (AEs) were mild or moderate in intensity, with no serious AEs or AEs leading to withdrawal reported in the double-blind period. AEs of special interest (urinary incontinence, anal sphincter atonia) were observed at low incidence and predominantly with higher aboBoNT-A doses. The dilator test composite score might be a useful endpoint for pain assessment, with a greater reduction in pain score noted for the 300 U dose group compared with other dose groups and placebo.

[CLINICAL IMPLICATIONS] aboBoNT-A was well tolerated in patients with PVD and a novel method for assessing dilator-induced pain was introduced.

[STRENGTHS AND LIMITATIONS] The study provided valuable data on use of aboBoNT-A in women with primary or secondary PVD and introduced a novel composite endpoint for assessing dilator-induced pain. Study limitations included the small sample size, limiting formal statistical analysis.

[CONCLUSION] aboBoNT-A was well tolerated in patients with PVD with no safety signals reported. Further studies are warranted to demonstrate clinically meaningful benefits with repeated treatment.

[CLINICAL TRIAL REGISTRATION NUMBER] NCT03598777.