Injectable DaxibotulinumtoxinA in Cervical Dystonia: A Phase 2 Dose-Escalation Multicenter Study

Abstract

Background: Injectable daxibotulinumtoxinA (an investigational botulinum toxin, RT002) may offer a more prolonged duration of response-and therefore less frequent dosing-than onabotulinumtoxinA.

Objectives: To perform a phase 2, open-label, dose-escalation study to assess the efficacy and safety of daxibotulinumtoxinA in cervical dystonia.

Methods: Subjects with moderate-to-severe isolated cervical dystonia were enrolled in sequential cohorts to receive a single open-label, intramuscular dose of injectable daxibotulinumtoxinA of up to 200 U (n = 12), 200-300 U (n = 12), or 300-450 U (n = 13; https://clinicaltrials.gov identifier NCT02706795).

Results: Overall, 33/37 enrollees completed the trial. DaxibotulinumtoxinA was associated with mean reductions in Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS)-Total score of 16.8 (38%) at week 4, 21.3 (50%) at week 6, and 12.8 (30%) at week 24. The proportion of subjects who were responders (achieved ≥ 20% reduction in TWSTRS-Total score) was 94% at week 6 and 68% at week 24. The median duration of response (time until > 20% of the improvement in TWSTRS-Total score achieved at week 4 was no longer retained or re-treatment was needed) was 25.3 weeks (95% CI, 20.14-26.14 weeks). There were no serious adverse events and there was no apparent dose-related increase in the incidence of adverse events. The most common treatment-related adverse events were dysphagia (14%) and injection site erythema (8%).

Conclusions: Preliminary assessments suggest that injectable daxibotulinumtoxinA at doses up to 450 U is well tolerated and may offer prolonged efficacy in the treatment of cervical dystonia. Further studies involving larger numbers of patients are now warranted.

Keywords: CDIP; TWSTRS; botulinum toxin; cervical dystonia; daxibotulinumtoxinA.

Figure 1

Study design and subject distribution by dose. ^aThree subjects had a protocol deviation as they remained in the study until Week 24 even though they had ceased to be treatment responders at an earlier visit (at week 20 for 2 subjects in cohort 2 and at week 6 for 1 subject in cohort 3).

Figure 2

Reduction in TWSTRS‐Total score and subscores for severity, disability, and pain in the lower‐dose and higher‐dose groups.

Figure 3

Response rate and duration of response. (A) Subjects achieving response (at least 20% improvement from baseline in TWSTRS‐Total score); (B) Subjects retaining at least 20% of the improvement in TWSTRS‐Total score achieved at week 4 (among subjects with improvement at week 4). Withdrawals due to need for re‐treatment are considered events. ^aOne subject was excluded from analysis as their TWSTRS score was not improved at week 4