Trial Outcomes & Findings for A Study to Compare the Safety and Efficacy of Dysport® and Botox® in Adults With Upper Limb Spasticity. (NCT NCT04936542)

This post-marketing, randomized, double-blind, crossover study was conducted in participants with upper limb spasticity.

A total of 464 participants were randomized in a 1:1 ratio to 1 of the 2 treatment sequences: sequence 1: abobotulinumtoxinA (aboBoNT-A) (Dysport \[test\]) in Cycle 1 followed by onabotulinumtoxinA (onaBoNT-A) (Botox \[reference\]) in Cycle 2 and sequence 2: onaBoNT-A in Cycle 1 followed by aboBoNT-A in Cycle 2.

As pre-specified in the protocol, ethnicity was only captured in the United States of America (USA). Only number of participants evaluable for the specified baseline measure are reported.

An AE was any untoward medical occurrence in a clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. A TEAE was defined for each treatment cycle as any AE that occurred during the cycle if it was not present prior to treatment injection, or it was present prior to treatment injection but the intensity increased during the cycle. Percentage of participants with TEAEs that occurred during each cycle from injection to 12 weeks after injection (until 84 days after injection or until the day prior to next injection day or until end of study/early withdrawal day whichever occurred first) is presented. Percentages are rounded off to the tenth decimal place.

AE: any untoward medical occurrence in a clinical study participant, temporally associated with use of study treatment, whether or not considered related to study treatment. SAE: any untoward medical occurrence that, at any dose: resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, was a suspected transmission of any infectious agent via an authorized medicinal product, or any other medically important event. TEAE for each treatment cycle: any AE that occurred during cycle if it was not present prior to treatment injection, or it was present prior to treatment injection but intensity increased during cycle. ADR: any TEAE that was assessed by Investigator as related to study treatment. AESI: TEAE that suggested a possible remote spread of toxin or events suggestive of hypersensitivity like reactions.

The duration of response was defined for Cycle 1 as time between Cycle 1 injection and the first Cycle 1 visit when retreatment criteria were met (from Week 10 visit), or time between Cycle 1 injection and study withdrawal if the participant discontinued from the study before Cycle 2 injection without meeting retreatment criteria; for Cycle 2 as time between Cycle 2 injection and the first Cycle 2 visit when retreatment criteria were met (from Week 10 visit), or time between Cycle 2 injection and end of study if the participant completed the study or discontinued from the study after Cycle 2 injection without meeting retreatment criteria. It was calculated as the date of retreatment criteria met or withdrawal date (or last visit date for lost to follow-up participants) or completion date - date of injection + 1.

Muscle tone for finger, wrist, elbow flexors assessed with MAS tool using scale: 0= no increase in muscle tone, 1= slight increase in muscle tone, manifested by a catch and release or by minimal resistance at end of range of motion (ROM) when affected part(s) was moved in flexion or extension, 1+= slight increase in muscle tone, manifested by a catch, followed by minimal resistance throughout remainder of ROM, 2= more marked increase in muscle tone through most of ROM, but affected part(s) easily moved, 3= considerable increase in muscle tone, passive movement difficult, 4= affected part(s) rigid in flexion or extension. PTMG included finger, wrist or elbow flexors which were selected by Investigators at screening as muscle group with highest MAS score. MAS total score was calculated as the sum of scores for all 3 joints (finger, wrist, elbow), ranged from: 0 (best) to 12 (worst); higher scores indicated worse outcomes.

The DAS was used to determine the extent of functional impairment in 4 domains: hygiene, dressing, limb position and pain. Impairment was assessed on a 4-point scale: 0= no disability, 1= mild disability (noticeable but did not interfere significantly with normal activities), 2= moderate disability (normal activities required increased effort and/or assistance) and 3= severe disability (normal activities limited). The 4 domain ratings were added to obtain DAS total score which ranged between 0 (best) and 12 (worst); higher scores indicated severe disability. The PTT was defined at screening as 1 of the 4 domains, with an associated DAS score for assessment.

The PGA of treatment response was assessed by asking the Investigator the following question: 'how would you rate the response to treatment in the participant's upper limb since the last injection?' and answered on a 9-point rating scale (-4: markedly worse, -3: much worse, -2: worse, -1: slightly worse, 0: no change, +1: slightly improved, +2: improved, +3: much improved and +4: markedly improved). Higher scores indicate greater better outcomes. 'Any improvement' in PGA was defined by a score including: +1, +2, +3 and +4.

SF-12 consisted of 12 questions \& asked respondent to answer questions as they pertained to way he/she felt or acted during past week. SF-12 covered 8 domains of health:physical functioning(PF),role physical(RP),bodily pain(BP),general health(GH),vitality(VT),social functioning(SF),role emotional(RE) \& mental health(MH). Score range for each of 8 domains:0(maximum disability) to 100(no disability);higher scores:good QoL. Responses on SF-12 were used to obtain 2 summary scores:PCS-12 contributed by PF,RP,BP, and GH and MCS-12 contributed by MH,RE,SF and VT. Summations of item scores of same domains gave sub-scale scores,which were transformed to obtain summary scores of PCS-12 \& MCS-12. Both PCS-12 \& MCS-12 scores ranged from 0(worst) to 100(best);higher scores:better QoL.Baseline:last non-missing measurement prior to first study treatment administration.Change from baseline in QoL assessed by SF-12 health survey perceived health score based on PCS-12 and MCS-12 scores is presented.

The SQoL-6D questionnaire was a brief questionnaire in 6 domains: pain/discomfort, involuntary movements or spasms, restricted range of movement, caring for the affected limb, using the affected limb and mobility/balance which was designed to assess QoL in relation to spasticity that affected the upper limb, which included the arm, shoulder or hand. Each dimension was assessed by asking participants about symptoms within the last 7 days, using a 5-level scale ranging from 0 (best) to 4 (worst); higher scores indicated worse condition. The mean of the 6-dimension scores was calculated to obtain the total score which ranged from 0 (worse) to 100 (best); higher score indicated better QoL. Baseline was defined as the last non-missing measurement prior to first study treatment administration. Change from Baseline in QoL assessed by SQoL-6D is presented.