Category: Clinical Sciences/Health Conditions
Objectives: To describe a novel study design utilizing pre-specified sample size adaptation based on an interim analysis to be used in the PATTERN study, which aims to investigate the efficacy and safety of incobotulinumtoxinA in the treatment of lower limb spasticity caused by stroke or traumatic brain injury
Design: Phase III, prospective, randomized, double-blind, placebo-controlled, multicenter study (NCT03992404), followed by open label extension (OLEX) period with or without combined upper limb treatment. A two-stage adaptive design with interim sample size re-assessment after 360 subjects will be applied. Setting: 60 clinical sites in North America, Europe, and Australia Participants: 600 adults. Interventions: In the Main Period (1 treatment cycle) subjects receive intramuscular injection of incobotulinumtoxinA (400 units) or placebo into lower limb muscles. In the OLEX Period (4-5 treatment cycles) subjects receive incobotulinumtoxinA (up to 800 units) into lower limb and upper limb muscles, if clinically indicated. Main Outcome Measures: At weeks 4-6, change from baseline in derived Modified Ashworth Scale-Bohannon (MAS) ankle score and Global Impression of Change Scale (GICS). A goal catalogue developed specifically for this population will be incorporated into the goal attainment scale (GAS) evaluation of treatment.
Results: The novel PATTERN study design allows for observation of up to 6 consecutive treatment cycles with an OLEX Period including a multi-pattern, patient-centric approach, if clinically indicated.
Conclusions: To our knowledge, this is the first time such an adaptive design is used for a BoNT study for lower limb spasticity.The novel design utilizing pre-specified sample size adaptation based on interim analysis in the PATTERN study demonstrates an innovative approach to the challenge of clinical studies for this indication. A goal catalogue derived from physicians’ and patients’ qualitative interviews is expected to overcome difficulties of comparable high-quality SMART (Specific, Measurable, Achievable, Realistic, Timed) treatment goal setting and follow-up in a large phase III trial.
Gerard Francisco– Chairman and Professor, Physical Medicine and Rehabilitation, University of Texas Health Science Center McGovern Medical School and TIRR Memorial Hermann
Joerg Wissel– Head of Department, Vivantes Hospital Spandau
Marta Banach– Associate Professor and Head of the Department of Clinical Neurophysiology, Jagiellonian University Medical College
Djamel Bensmail– Head of PRM unit, R. Poincaré Hospital / University of Versailles Saint Quentin
Franco Molteni– Director, H.Valduce Villa Beretta Rehabilitation Center
Alberto Esquenazi– Chief Medical Officer, MossRehab Gait and Motion Analysis Laboratory
Michael Munin– Professor, UPMC
Hanna Dersch– Biostatistician, Merz Pharmaceuticals GmbH
Thorin Geister– Lead Scientific Expert Evidence-Based Medicine, Merz Pharmaceuticals GmbH
Michael Althaus– principal medical expert, Merz pharmaceuticals