Disclosures: Alberto Esquenazi, MD: Allergan (Products/Services: Yes) (Consultant/Advisory Board, Research Grant includes principal investigator, collaborator or consultant and pending grants as well as grants already received)Ipsen (Products/Services: Yes, No) (Consultant/Advisory Board, Research Grant includes principal investigator, collaborator or consultant and pending grants as well as grants already received)Merz (Products/Services: Yes) (Research Grant includes principal investigator, collaborator or consultant and pending grants as well as grants already received)

Objective: Evaluate the safety and efficacy of abobotulinumtoxinA in comparison to onabotulinumtoxinA when used at optimized doses in approved muscles common to both products’ US FDA labels.

Design: Phase IV, interventional, randomized, double-blind, crossover study.Setting : International (including USA, Canada and France) study at physical rehabilitation centers.Participants : An estimated 650 participants (18-75y) with upper-limb spasticity will be screened to achieve enrolment of 564 randomized patients.

Interventions: Participants will be randomized (1:1) to two treatment sequences – either one cycle of abobotulinumtoxinA (900U) followed by one cycle of onabotulinumtoxinA (360U) or vice versa. To maintain study blinding, a fixed volume of study intervention (3.6mL) will be injected into the target upper-limb muscles (4 palmar flexors and biceps brachii) using guidance techniques. Participants will begin the second treatment cycle at Week 12 if retreatment criteria are fulfilled. If not, participants will be reassessed every 4 weeks (at Week 16, Week 20 and Week 24) until they require retreatment.

Main Outcome Measures: The primary hypothesis is that the safety profiles of both products are comparable (non-inferiority will be tested based on TEAE rates from injection to Week 12). A secondary hypothesis is that abobotulinumtoxinA has longer duration of effect than onabotulinumtoxinA; this hypothesis will be based on superiority tests associated with secondary efficacy endpoints analyses (including injection cycle duration, Modified Ashworth Scale, Disability Assessment Scale and Physician Global Assessment).

Results: The DIRECTION study will complete in 2023.Conclusions: The safety and efficacy of both abobotulinumtoxinA and onabotulinumtoxinA for upper-limb spasticity has previously been established (Level 1), but head-to-head comparisons are lacking. Using clinically relevant dosing, the DIRECTION study will be the first to prospectively compare abobotulinumtoxinA with onabotulinumtoxinA to allow informed therapeutic decisions for care optimization, including use of optimized dosing- according to the approved prescribing information.

Level of Evidence: Level I

« Back to AAPM&R Annual Assembly 2021

PM&R Meeting Abstracts - https://pmrjabstracts.org/abstract/a-phase-iv-randomized-double-blind-cross-over-study-comparing-the-clinical-safety-efficacy-and-duration-of-abobotulinumtoxina-with-onabotulinumtoxina-in-adults-with-upper-limb-spasticity/