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

Joseph Jankovic, Daniel Truong, Atul T Patel, Allison Brashear, Marian Evatt, Roman G Rubio, Chad K Oh, Daniel Snyder, Gill Shears, Cynthia Comella, Joseph Jankovic, Daniel Truong, Atul T Patel, Allison Brashear, Marian Evatt, Roman G Rubio, Chad K Oh, Daniel Snyder, Gill Shears, Cynthia Comella

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://ichgcp.net/clinical-trials-registry/NCT02706795" title="See in ClinicalTrials.gov">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.

Figures

Figure 1
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
Figure 2
Reduction in TWSTRS‐Total score and subscores for severity, disability, and pain in the lower‐dose and higher‐dose groups.
Figure 3
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

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Source: PubMed

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