Efficacy, Safety and Pharmacokinetics of BI 655066/ABBV-066 (Risankizumab) in Patients With Active, Moderate-to-severe Crohn's Disease.
- Conditions
- Crohn Disease
- Interventions
- Registration Number
- NCT02031276
- Lead Sponsor
- AbbVie
- Brief Summary
This study is a proof of concept, multi-center, randomized, double-blind, placebo-controlled, parallel-group phase 2 dose-ranging study of BI 655066/ABBV-066 (risankizumab), an IL-23 p19 antagonist monoclonal antibody, in patients with moderately to severely active Crohn's disease.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 121
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Double-blind Placebo IV risankizumab SC Participants randomized to receive double-blind placebo for risankizumab by intravenous (IV) injection for 12 weeks in Period 1, followed by open-label risankizumab 600 mg IV in Period 2, then open-label risankizumab 180 mg by subcutaneous (SC) injection in Period 3. Double-blind Placebo IV risankizumab IV Participants randomized to receive double-blind placebo for risankizumab by intravenous (IV) injection for 12 weeks in Period 1, followed by open-label risankizumab 600 mg IV in Period 2, then open-label risankizumab 180 mg by subcutaneous (SC) injection in Period 3. Double-blind Risankizumab 200 mg IV risankizumab SC Participants randomized to receive double-blind risankizumab 200 mg by intravenous (IV) injection for 12 weeks in Period 1, followed by open-label risankizumab 600 mg IV in Period 2, then open-label risankizumab 180 mg by subcutaneous (SC) injection in Period 3. Double-blind Risankizumab 200 mg IV risankizumab IV Participants randomized to receive double-blind risankizumab 200 mg by intravenous (IV) injection for 12 weeks in Period 1, followed by open-label risankizumab 600 mg IV in Period 2, then open-label risankizumab 180 mg by subcutaneous (SC) injection in Period 3. Double-blind Risankizumab 600 mg IV risankizumab IV Participants randomized to receive double-blind risankizumab 600 mg by intravenous (IV) injection for 12 weeks in Period 1, followed by open-label risankizumab 600 mg IV in Period 2, then open-label risankizumab 180 mg by subcutaneous (SC) injection in Period 3. Double-blind Risankizumab 600 mg IV risankizumab SC Participants randomized to receive double-blind risankizumab 600 mg by intravenous (IV) injection for 12 weeks in Period 1, followed by open-label risankizumab 600 mg IV in Period 2, then open-label risankizumab 180 mg by subcutaneous (SC) injection in Period 3. Double-blind Placebo IV Placebo Participants randomized to receive double-blind placebo for risankizumab by intravenous (IV) injection for 12 weeks in Period 1, followed by open-label risankizumab 600 mg IV in Period 2, then open-label risankizumab 180 mg by subcutaneous (SC) injection in Period 3.
- Primary Outcome Measures
Name Time Method Percentage of Participants Achieving Clinical Disease Activity Index (CDAI) Clinical Remission at Week 12 Week 12 The CDAI is a measure of clinical response and remission. The CDAI includes 8 variables encompassing both patient-reported (symptoms, general well-being) and objective (medication usage, laboratory variables, presence of abdominal mass or complications, and weight) variables. For symptoms scores, patients keep track of daily symptoms on a diary card and the daily symptom scores are summed for the week. Each item in the CDAI is assigned a specific weight, and the weighted values of the items are totaled to produce the CDAI. Higher CDAI scores indicate greater disease activity, with a lower limit of 0 and no set upper limit: \< 150 indicates remission, 150 - 219 indicates mildly active disease, 220 - 450 indicates moderately active disease, and \> 450 indicates severely active disease. CDAI clinical remission is defined as CDAI \< 150 at Week 12. Nonresponder imputation (NRI): missing values were counted as nonresponders.
- Secondary Outcome Measures
Name Time Method Percentage of Participants Achieving Crohn's Disease Endoscopic Index of Severity (CDEIS) Remission at Week 12 Week 12 CDEIS is an index for determining the severity of Crohn's disease with endoscopic localization to ileum and colon. CDEIS considers 4 parameters (deep ulcerations, superficial ulcerations, surface involved by disease, and surface involved by ulcerations), each one evaluated in 5 pre-defined segments of the colon (ileum, ascending colon, transverse colon, descending colon and sigmoid loop, and rectum). The results of the individual segments of the colon are divided by the number of segments investigated; the presence of stenosis increases the score at the end of the computation. CDEIS remission is defined as a CDEIS ≤ 4 (or, for patients with initial isolated ileitis, a CDEIS ≤ 2) at Week 12. NRI: missing values were counted as nonresponders.
Percentage of Participants Achieving Deep Remission at Week 12 Week 12 Deep remission is defined as clinical remission (CDAI \< 150) AND CDEIS remission (CDEIS ≤ 4, or ≤ 2 in participants with initial isolated ileitis) at Week 12. NRI: missing values were counted as nonresponders.
Percentage of Participants Achieving Mucosal Healing at Week 12 Week 12 Mucosal healing was defined as the absence of mucosal ulceration, i.e., a CDEIS ulceration sub-score (deep ulceration, superficial ulceration, ulcerated stenosis) of 0 at Week 12. NRI: missing values were counted as nonresponders.
Percentage of Participants Achieving CDAI Clinical Response at Week 12 Week 12 The CDAI is a measure of clinical response and remission. The CDAI includes 8 variables encompassing both patient-reported (symptoms, general well-being) and objective (medication usage, laboratory variables, presence of abdominal mass or complications, and weight) variables. For symptoms scores, patients keep track of daily symptoms on a diary card and the daily symptom scores are summed for the week. Each item in the CDAI is assigned a specific weight, and the weighted values of the items are totaled to produce the CDAI. Higher CDAI scores indicate greater disease activity, with a lower limit of 0 and no set upper limit: \< 150 indicates remission, 150 - 219 indicates mildly active disease, 220 - 450 indicates moderately active disease, and \> 450 indicates severely active disease. CDAI clinical response is defined as either a CDAI \< 150 or a CDAI reduction from Baseline of at least 100 points at Week 12. NRI: missing values were counted as nonresponders.
Percentage of Participants Achieving CDEIS Response at Week 12 Week 12 CDEIS is an index for determining the severity of Crohn's disease with endoscopic localization to ileum and colon. CDEIS considers 4 parameters (deep ulcerations, superficial ulcerations, surface involved by disease, and surface involved by ulcerations), each one evaluated in 5 pre-defined segments of the colon (ileum, ascending colon, transverse colon, descending colon and sigmoid loop, and rectum). The results of the individual segments of the colon are divided by the number of segments investigated; the presence of stenosis increases the score at the end of the computation. CDEIS response is defined as defined as ≥ 50% reduction of CDEIS from Baseline to Week 12. NRI: missing values were counted as nonresponders.