AbbVie – Risankizumab is a fully humanized monoclonal antibody of the IgG1 subclass directed towards IL (interleukin)-23p19. Risankizumab binds with high affinity to human IL-23 and inhibits IL-23 stimulated IL-17 production. Study M16-006 is a randomized, double blind, placebo-controlled 12-week induction study. Subjects (n = 940) will be randomized 2:2:1 to 1200 mg risankizumab or 600 mg risankizumab or placebo intravenous (IV) given at Baseline, Weeks 4 and 8. The randomization will be stratified by number of prior biologics failed (0, 1, > 1) and Baseline steroid use (yes, no). Visits during the study will occur at Baseline and Weeks 4, 8, and 12/Premature Discontinuation (PD) to collect clinical and laboratory assessments of disease activity. Subjects who do not achieve clinical response at Week 12 will be offered blinded risankizumab therapy in Induction Period 2 with evaluation for clinical response at Week 24.
All subjects will be provided with a subject diary where they will record CD related symptoms throughout the study. Subjects will also be dispensed a patient information card at Screening. Additionally, subjects will complete symptom, quality of life (QoL) and work productivity questionnaires throughout the study. Clinical labs including, but not limited to, urinalysis, chemistry and hematology, high-sensitivity C-reactive protein (hs-CRP), serum risankizumab concentrations, and serum anti-drug antibody (ADA) levels will be collected throughout the study. In addition, stool samples for calprotectin analysis will be collected and should be taken before starting bowel preparations for endoscopy. All endoscopies will be evaluated using SES-CD and will be confirmed by a central reader. Biopsy to confirm diagnosis (during Screening) or to rule out dysplasia/malignancy may be performed during the same time points as the endoscopy. Optional exploratory research samples may be taken during the study. At the Week 12/PD visit, all subjects will undergo an endoscopy for evaluation of mucosal inflammation.
It is expected that all subjects who remain in the study through at least Week 8 will have a Week 12/PD endoscopy. All subjects achieving clinical response, defined as ≥ 30% decrease in average daily SF and/or ≥ 30% decrease in average daily AP score (both not worse than Baseline) at Week 12 may be eligible to enter Study M16-000. Subjects are not eligible to enter Study M16-000 until endoscopy has been completed (local reader results will be used for stratification for Study M16-000). All subjects who do not achieve clinical response at Week 12 may be eligible to receive blinded risankizumab treatment in Induction Period 2 as specified below. Subjects are not eligible to enter Induction Period 2 until the Week 12 endoscopy has been completed.