Clinical trial NCT02365649: A Multicenter, Randomized, Double-Blind, Placebo-Controlled Study of ABT-494 for the Induction of Symptomatic and Endoscopic Remission in Subjects With Moderately to Severely Active Crohn's Disease Who Have Inadequately Responded to or Are Intolerant to Immunomodulators or Anti-TNF Therapy
Official title: A Multicenter, Randomized, Double-Blind, Placebo-Controlled Study of Upadacitinib (ABT-494) for the Induction of Symptomatic and Endoscopic Remission in Subjects With Moderately to Severely Active Crohn's Disease Who Have Inadequately Responded to or Are Intolerant to Immunomodulators or Anti-TNF Therapy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Crohn's Disease
Keywords: Crohn's Disease
Lead sponsor: AbbVie
Sponsor class: INDUSTRY
First posted: 2015-02-19
Enrollment: 220
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: To determine the efficacy and safety of multiple doses of ABT-494 in subjects with moderately to severely active Crohn's Disease with a history of inadequate response to or intolerance to Immunomodulators or anti-Tumor Necrosis Factor (TNF) therapy.


Eligibility criteria: Inclusion Criteria:

1. Diagnosis of Crohn's disease (CD) for at least 90 days.
2. Crohn's Disease Activity Index (CDAI) greater than or equal to 220 and less than or equal to 450.
3. Subject inadequately responded to or experienced intolerance to previous treatment with immunomodulators (e.g. azathioprine, 6-mercaptopurine, or methotrexate) and/or anti-TNF agent (e.g., infliximab, adalimumab, or certolizumab pegol).

Exclusion Criteria:

1. Subjects with ulcerative colitis (UC), collagenous colitis or indeterminate colitis.
2. Subject who has had surgical bowel resections in the past 6 months or is planning resection.
3. Subjects with an ostomy or ileoanal pouch.
4. Subject with symptomatic bowel stricture or abdominal or peri-anal abcess.
5. Subject who has short bowel syndrome.
6. Subject with recurring infections or active Tuberculosis (TB).

Primary outcomes:
measure: Percentage of Participants Who Achieve Endoscopic Remission at Week 12/16
timeFrame: Up to Week 16. (At Baseline, participants were allocated by randomization 1:1 to have their end of induction colonoscopy done at either Week 12 or Week 16; this endpoint combines the two time points.)
measure: Percentage of Participants Who Achieve Clinical Remission at Week 16
timeFrame: Week 16
Secondary outcomes:
measure: Percentage of Participants Who Achieve Crohn's Disease Activity Index (CDAI) < 150 at Week 16
timeFrame: Week 16
measure: Percentage of Participants With a Decrease in CDAI ≥ 70 Points From Baseline at Week 16
timeFrame: Week 16
measure: Percentage of Participants Who Achieve Clinical Remission at Week 12
timeFrame: Week 12
measure: Percentage of Participants Who Achieve Remission at Week 16
timeFrame: Week 16
measure: Percentage of Participants Who Achieve Response at Week 16
timeFrame: Week 16
measure: Percentage of Participants With Endoscopic Response at Week 12/16
timeFrame: Up to Week 16 (At Baseline, participants were allocated by randomization 1:1 to have their end of induction colonoscopy done at either Week 12 or Week 16; this endpoint combines the two time points.)
measure: Percentage of Participants Who Achieve Clinical Response at Week 16
timeFrame: Week 16
measure: Percentage of Participants With an Average Daily Stool Frequency ≥ 2.5 AND Average Daily Abdominal Pain ≥ 2.0 at Baseline Who Achieve Clinical Remission at Week 16
timeFrame: Week 16
measure: Percentage of Participants Taking Corticosteroids at Baseline Who Discontinued Corticosteroid Use and Achieve CDAI < 150 at Week 16
timeFrame: Week 16
measure: Percentage of Participants Taking Corticosteroids at Baseline Who Discontinued Corticosteroid Use and Achieve Remission at Week 12/16 and Clinical Remission at Week 16
timeFrame: Up to Week 16. (At Baseline, subjects were allocated by randomization 1:1 to have their end of induction colonoscopy done at either Week 12 or Week 16; this endpoint combines the two time points.)
measure: Percentage of Participants Taking Corticosteroids at Baseline Who Discontinued Corticosteroid Use and Achieve Clinical Remission at Week 16
timeFrame: Week 16
measure: Percentage of Participants Taking Corticosteroids at Baseline Who Discontinued Corticosteroid Use and Achieve Endoscopic Remission at Week 12/16
timeFrame: Up to Week 16. (At Baseline, participants were allocated by randomization 1:1 to have their end of induction colonoscopy done at either Week 12 or Week 16; this endpoint combines the two time points.)
measure: Change From Baseline in Fecal Calprotectin Level Over Time During the Induction Phase
timeFrame: Baseline, Week 4, Week 16
measure: Change From Baseline in High-Sensitivity C-Reactive Protein (Hs-CRP) at Week 16
timeFrame: Baseline, Week 16
measure: Change From Baseline in Inflammatory Bowel Disease Questionnaire (IBDQ) Over Time During the Induction Phase
timeFrame: Baseline, Week 8, Week 16
measure: Percentage of Participants With Isolated Ileal Crohn's Disease at Baseline Who Achieve Remission at Week 16
timeFrame: Week 16
measure: Percentage of Participants With a Decrease in CDAI ≥ 100 Points From Baseline at Week 16
timeFrame: Week 16
measure: Percentage of Participants Who Achieve > 50% Reduction From Baseline in SES-CD or Endoscopic Remission at Week 12/16
timeFrame: Up to Week 16. (At Baseline, participants were allocated by randomization 1:1 to have their end of induction colonoscopy done at either Week 12 or Week 16; this endpoint combines the two time points.)
measure: Percentage of Participants Who Achieve Modified Clinical Remission at Week 16 Among Participants With an Average Daily Stool Frequency ≥ 4.0 or Average Daily Abdominal Pain ≥ 2.0 at Baseline
timeFrame: Week 16
measure: Change From Baseline in Abdominal Pain Rating Scale at Week 12
timeFrame: Baseline, Week 12
measure: Change From Baseline in Abdominal Pain Rating Scale at Week 16
timeFrame: Baseline, Week 16
measure: Percentage of Participants Who Achieve Remission at Week 52
timeFrame: Week 52
measure: Percentage of Participants Who Achieve Endoscopic Remission at Week 52
timeFrame: Week 52
measure: Percentage of Participants Who Achieve Both Endoscopic Remission and Modified Clinical Remission at Week 52 Among Subjects With Daily Stool Frequency ≥ 4.0 or Daily Abdominal Pain ≥ 2.0 at Induction Baseline
timeFrame: Week 52
measure: Percentage of Participants Who Achieve Clinical Remission Over Time During Extension Phase in Participants Receiving Upadacitinib in Induction
timeFrame: Week 20, Week 28, Week 36, Week 44, Week 52
measure: Percentage of Participants Who Maintain Clinical Remission Over Time Among Participants in Clinical Remission at Week 16 in Participants Receiving Upadacitinib in Induction
timeFrame: Week 20, Week 28, Week 36, Week 44, Week 52
measure: Percentage of Participants Who Achieve Modified Clinical Remission Over Time During Extension Phase Among Participants With Daily Stool Frequency ≥ 4.0 or Daily Abdominal Pain ≥ 2.0 at Induction Baseline
timeFrame: Week 20, Week 28, Week 36, Week 44, Week 52
measure: Percentage of Participants Who Achieve Modified Clinical Remission Over Time During Extension Phase Among Participants In Modified Clinical Remission At Week 16 and Daily Stool Frequency ≥ 4.0 or Daily Abdominal Pain ≥ 2.0 at Induction Baseline
timeFrame: Week 20, Week 28, Week 36, Week 44, Week 52
measure: Percentage of Participants Who Achieve Response at Week 52
timeFrame: Week 52
measure: Percentage of Participants With SES-CD ≤ 2 at Week 52
timeFrame: Week 52
measure: Percentage of Participants With SES-CD = 0 at Week 52
timeFrame: Week 52
measure: Percentage of Participants Who Achieve Endoscopic Response at Week 52
timeFrame: Week 52
measure: Percentage of Participants Who Achieve Enhanced Endoscopic Response at Week 52
timeFrame: Week 52
measure: Percentage of Participants Who Achieve Endoscopic Improvement at Week 52
timeFrame: Week 52
measure: Percentage of Participants Who Achieve Endoscopic Healing at Week 52
timeFrame: Week 52
measure: Percentage of Participants Who Achieve Clinical Response Over Time During Extension Phase
timeFrame: Week 20, Week 28, Week 36, Week 44, Week 52
measure: Percentage of Participants Who Achieve Enhanced Clinical Response Over Time During Extension Phase
timeFrame: Week 20, Week 28, Week 36, Week 44, Week 52
measure: Percentage of Participants Who Achieve Enhanced Clinical Response Over Time During Extension Phase Among Participants In Enhanced Clinical Response At Week 16
timeFrame: Week 20, Week 28, Week 36, Week 44, Week 52
measure: Percentage of Participants Who Achieve Clinical Remission Over Time During Extension Phase Among Participants With an Average Daily Stool Frequency ≥ 2.5 and Average Daily Abdominal Pain ≥ 2.0 at Induction Baseline
timeFrame: Week 20, Week 28, Week 36, Week 44, Week 52
measure: Percentage of Participants Taking Corticosteroids at Induction Baseline Who Discontinued Corticosteroid Use and Achieve CDAI < 150 Over Time
timeFrame: Week 20, Week 28, Week 36, Week 44, Week 52
measure: Percentage of Participants Taking Corticosteroids at Induction Baseline Who Discontinued Corticosteroid Use and Achieve Remission At Week 52
timeFrame: Baseline, Week 52
measure: Percentage of Participants Taking Corticosteroids at Induction Baseline Who Discontinued Corticosteroid Use and Achieve Clinical Remission Over Time
timeFrame: Week 20, Week 28, Week 36, Week 44, Week 52
measure: Percentage of Participants Taking Corticosteroids at Induction Baseline and With Daily Stool Frequency ≥ 4.0 or Daily Abdominal Pain ≥ 2.0 at Induction Baseline Who Discontinued Corticosteroid Use and Achieve Modified Clinical Remission Over Time
timeFrame: Week 20, Week 28, Week 36, Week 44, Week 52
measure: Percentage of Participants Taking Corticosteroids at Induction Baseline Who Discontinued Corticosteroid Use and Achieve Endoscopic Remission at Week 52
timeFrame: Baseline, Week 52
measure: Percentage Of Participants Who Achieve CDAI < 150 Over Time During Extension Phase
timeFrame: Week 20, Week 28, Week 36, Week 44, Week 52
measure: Percentage of Participants With Decrease in CDAI ≥ 70 Points From Induction Baseline Over Time During Extension Phase
timeFrame: Week 20, Week 28, Week 36, Week 44, Week 52
measure: Change From Induction Baseline in Fecal Calprotectin Level Over Time During Extension Phase
timeFrame: Baseline, Week 28, Week 52
measure: Change From Induction Baseline in Hs-CRP Over Time During Extension Phase
timeFrame: Baseline, Week 20, Week 28, Week 36, Week 44, Week 52
measure: Change From Induction Baseline in IBDQ at Week 52
timeFrame: Baseline, Week 52
measure: Change From Induction Baseline in European Quality of Life (EuroQol) 5 Dimensions Questionnaire (EQ-5D) Index Score at Week 52
timeFrame: Baseline, Week 52
measure: Change From Induction Baseline in EQ-5D VAS at Week 52
timeFrame: Baseline, Week 52
measure: Cross Tabulation of Induction Baseline and Week 52 in Total Number of Extra-Intestinal Manifestations (EIMs) of Crohn's Disease
timeFrame: Baseline, Week 52
measure: Percentage of Participants Who Achieve Remission at Week 52 Among Participants With Isolated Ileal Crohn's Disease at Baseline
timeFrame: Baseline, Week 52
measure: Percentage of Participants Who Achieve Modified Clinical Remission at Week 52 Among Participants With Isolated Ileal Crohn's Disease at Baseline And Daily Stool Frequency ≥ 4.0 or Daily Abdominal Pain ≥ 2.0 at Induction Baseline
timeFrame: Week 52
Other outcomes:
Locations:
Study officials:
affiliation: AbbVie
name: AbbVie Inc.
role: STUDY_DIRECTOR
References:
citation: Sandborn WJ, Lewis JD, Panes J, Loftus EV, D'Haens G, Yu Z, Huang B, Lacerda AP, Pangan AL, Feagan BG. Association Between Proposed Definitions of Clinical Remission/Response and Well-Being in Patients With Crohn's Disease. J Crohns Colitis. 2022 Mar 14;16(3):444-451. doi: 10.1093/ecco-jcc/jjab161.
citation: Aguilar D, Revilla L, Garrido-Trigo A, Panes J, Lozano JJ, Planell N, Esteller M, Lacerda AP, Guay H, Butler J, Davis JW, Salas A. Randomized Controlled Trial Substudy of Cell-specific Mechanisms of Janus Kinase 1 Inhibition With Upadacitinib in the Crohn's Disease Intestinal Mucosa: Analysis From the CELEST Study. Inflamm Bowel Dis. 2021 Nov 15;27(12):1999-2009. doi: 10.1093/ibd/izab116.
citation: Peyrin-Biroulet L, Louis E, Loftus EV Jr, Lacerda A, Zhou Q, Sanchez Gonzalez Y, Ghosh S. Quality of Life and Work Productivity Improvements with Upadacitinib: Phase 2b Evidence from Patients with Moderate to Severe Crohn's Disease. Adv Ther. 2021 May;38(5):2339-2352. doi: 10.1007/s12325-021-01660-7. Epub 2021 Mar 23.
citation: Sandborn WJ, Feagan BG, Loftus EV Jr, Peyrin-Biroulet L, Van Assche G, D'Haens G, Schreiber S, Colombel JF, Lewis JD, Ghosh S, Armuzzi A, Scherl E, Herfarth H, Vitale L, Mohamed MF, Othman AA, Zhou Q, Huang B, Thakkar RB, Pangan AL, Lacerda AP, Panes J. Efficacy and Safety of Upadacitinib in a Randomized Trial of Patients With Crohn's Disease. Gastroenterology. 2020 Jun;158(8):2123-2138.e8. doi: 10.1053/j.gastro.2020.01.047. Epub 2020 Feb 8.