Multi-level and Multi-pattern Lower- and Upper-limb Spasticity Treatment with IncobotulinumtoxinA in Children and Adolescents with Cerebral Palsy (1548)

Objective: Assess efficacy and safety of incobotulinumtoxinA in lower-limb (LL) or combined LL/upper-limb (LL/UL) spasticity in children and adolescents with cerebral palsy (CP). Background: Spasticity is the most prominent movement disorder in children with CP. Design/Methods: Two phase III studies; a lead-in prospective, double-blind, randomized study (TIM) followed by an open-label, non-controlled study (TIMO). TIM had three parallel dose groups (4 U/kg body weight (BW), 12 U/kg BW, 16 U/kg BW); subjects were randomized in a 1:1:2 ratio and received 2 double-blind injection cycles. In TIMO, subjects who had completed TIM, or newly recruited treatment-naive or pre-treated subjects, received 4 injection cycles with the highest dose of TIM. The primary endpoints of TIM were change from baseline in Ashworth Scale (AS) of the plantar flexors (PF) score at Week 4 of Cycle 1, and the Investigator’s Global Impression of Change of Plantar Flexor Spasticity Scale (GICS-PF) score at Week 4 of Cycle 1. TIMO was focused on safety, and did not have primary efficacy endpoints. Results: In TIM, all 3 dose groups experienced a statistically significant improvement in AS-PF score 4 weeks post-injection versus baseline. In TIMO, cumulative improvements in AS scores for the PF, knee flexors and thigh adductors were observed from TIM baseline to 4 weeks post-injection. Investigator’s GICS-PF scores indicated a positive response to treatment in all dose groups 4 weeks post-injection in TIM Cycle 1 and improvements were maintained in all treatment groups in Cycle 2. Respective clinical assessments also confirmed consistent improvement in LL and UL spasticity at Week 4 in all TIMO injection cycles. Both studies had good overall safety profiles. Conclusions: IncobotulinumtoxinA at total doses up to 16–20 U/kg is effective and well tolerated for the multi-level, multi-pattern treatment of LL/UL spasticity due to CP in children and adolescents. Disclosure: Dr. Dabrowski has nothing to disclose. Dr. Chambers has nothing to disclose. Dr. Heinen has nothing to disclose. Dr. Kanovsky has nothing to disclose. Dr. Schroeder has nothing to disclose. Dr. Graham has nothing to disclose. Dr. Banach has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Merz. Dr. Banach has received research support from Merz, Ipsen, Kedrion, Shire, Allergan. Dr. Dersch has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Merz Pharmaceuticals GmBH. Dr. Geister has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Merz Pharmaceuticals GmBH. Dr. Martinez-Torres has nothing to disclose. Dr. Pulte has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Merz Pharmaceuticals GmBH. Dr. Gaebler-Spira has nothing to disclose.