Phase 2
N=220
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
Crohn's Disease
Bottom Line
View on ClinicalTrials.gov: NCT02365649 ↗Enrolled (actual)
220
Serious AEs
16.2%
Results posted
Aug 2023
Primary outcome: Primary: Percentage of Participants Who Achieve Endoscopic Remission at Week 12/16 — 0; 10.3; 8.1; 8.3 percentage of participants — p=0.056
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- Placebo (Drug); ABT-494 (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- AbbVie
- Primary completion
- Nov 2016
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Percentage of Participants Who Achieve Endoscopic Remission at Week 12/16 |
0; 10.3; 8.1; 8.3; 22.2; 14.3 | 0.056 |
| PRIMARY Percentage of Participants Who Achieve Clinical Remission at Week 16 |
10.8; 12.8; 27.0; 11.1; 22.2; 14.3 | 0.74 |
| SECONDARY Percentage of Participants Who Achieve Crohn's Disease Activity Index (CDAI) < 150 at Week 16 |
16.2; 20.5; 29.7; 38.9; 30.6; 20.0 | 0.564 |
| SECONDARY Percentage of Participants With a Decrease in CDAI ≥ 70 Points From Baseline at Week 16 |
35.1; 46.2; 54.1; 44.4; 61.1; 48.6 | 0.363 |
| SECONDARY Percentage of Participants Who Achieve Clinical Remission at Week 12 |
10.8; 10.3; 29.7; 13.9; 25.0; 8.6 | 0.896 |
| SECONDARY Percentage of Participants Who Achieve Remission at Week 16 |
0.0; 2.6; 5.4; 2.8; 8.3; 5.7 | 0.276 |
| SECONDARY Percentage of Participants Who Achieve Response at Week 16 |
2.7; 15.4; 32.4; 27.8; 38.9; 34.3 | 0.05 |
| SECONDARY Percentage of Participants With Endoscopic Response at Week 12/16 |
13.5; 23.1; 43.2; 36.1; 50.0; 48.6 | 0.243 |
| SECONDARY Percentage of Participants Who Achieve Clinical Response at Week 16 |
32.4; 43.6; 56.8; 47.2; 61.1; 48.6 | 0.353 |
| SECONDARY 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 |
7.1; 17.6; 18.8; 16.7; 25.0; 11.1 | 0.421 |
| SECONDARY Percentage of Participants Taking Corticosteroids at Baseline Who Discontinued Corticosteroid Use and Achieve CDAI < 150 at Week 16 |
0.0; 19.0; 22.2; 41.2; 33.3; 10.0 | 0.093 |
| SECONDARY Percentage of Participants Taking Corticosteroids at Baseline Who Discontinued Corticosteroid Use and Achieve Remission at Week 12/16 and Clinical Remission at Week 16 |
0.0; 0.0; 5.6; 5.9; 13.3; 0.0 | 0.564 |
| SECONDARY Percentage of Participants Taking Corticosteroids at Baseline Who Discontinued Corticosteroid Use and Achieve Clinical Remission at Week 16 |
0.0; 14.3; 22.2; 11.8; 33.3; 10.0 | 0.195 |
| SECONDARY Percentage of Participants Taking Corticosteroids at Baseline Who Discontinued Corticosteroid Use and Achieve Endoscopic Remission at Week 12/16 |
0.0; 0.0; 11.1; 5.9; 20.0; 10.0 | 0.392 |
| SECONDARY Change From Baseline in Fecal Calprotectin Level Over Time During the Induction Phase |
83.7; -310.3; -436.9; -915.7; -876.2; -255.8 | 0.788 |
| SECONDARY Change From Baseline in High-Sensitivity C-Reactive Protein (Hs-CRP) at Week 16 |
-0.1; -3.0; -3.9; -6.1; -14.8; -2.7 | 0.921 |
| SECONDARY Change From Baseline in Inflammatory Bowel Disease Questionnaire (IBDQ) Over Time During the Induction Phase |
16.6; 18.9; 34.6; 24.9; 39.7; 23.3 | 0.830 |
| SECONDARY Percentage of Participants With Isolated Ileal Crohn's Disease at Baseline Who Achieve Remission at Week 16 |
0.0; 20.0; 16.7; 20.0; 0.0; 20.0 | 0.167 |
| SECONDARY Percentage of Participants With a Decrease in CDAI ≥ 100 Points From Baseline at Week 16 |
27.0; 33.3; 40.5; 44.4; 55.6; 31.4 | 0.607 |
| SECONDARY Percentage of Participants Who Achieve > 50% Reduction From Baseline in SES-CD or Endoscopic Remission at Week 12/16 |
2.7; 12.8; 18.9; 25.0; 36.1; 25.7 | 0.119 |
| SECONDARY 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 |
12.1; 15.8; 30.3; 26.5; 36.7; 18.8 | 0.647 |
| SECONDARY Change From Baseline in Abdominal Pain Rating Scale at Week 12 |
-1.1; -1.0; -2.6; -2.4; -2.7; -1.0 | 0.412 |
| SECONDARY Change From Baseline in Abdominal Pain Rating Scale at Week 16 |
-0.9; -1.7; -2.8; -1.7; -2.3; -1.4 | 0.314 |
| SECONDARY Percentage of Participants Who Achieve Remission at Week 52 |
20.0; 12.5; 25.0; 0.0; 0.0; 0.0 | 1.000 |
| SECONDARY Percentage of Participants Who Achieve Endoscopic Remission at Week 52 |
25.0; 25.0; 37.5; 10.0; 0; 3.1 | 1.000 |
| SECONDARY 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 |
29.4; 12.5; 33.3; 10.0; 0; 0 | 0.624 |
| SECONDARY Percentage of Participants Who Achieve Clinical Remission Over Time During Extension Phase in Participants Receiving Upadacitinib in Induction |
45.0; 37.5; 50.0; 40.0; 45.0; 37.5 | 1.000 |
| SECONDARY Percentage of Participants Who Maintain Clinical Remission Over Time Among Participants in Clinical Remission at Week 16 in Participants Receiving Upadacitinib in Induction |
80.0; 66.7; 71.4; 100; 90.0; 66.7 | 1.000 |
| SECONDARY 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 |
47.1; 62.5; 66.7; 60.0; 0; 70.6 | 0.673 |
| SECONDARY 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 |
66.7; 60.0; 90.0; 100; 91.7; 60.0 | 1.000 |
| SECONDARY Percentage of Participants Who Achieve Response at Week 52 |
50.0; 62.5; 68.8; 40.0; 100; 6.3 | 0.686 |
| SECONDARY Percentage of Participants With SES-CD ≤ 2 at Week 52 |
10.0; 12.5; 31.3; 0; 0; 6.3 | 1.000 |
| SECONDARY Percentage of Participants With SES-CD = 0 at Week 52 |
10.0; 12.5; 31.3; 0; 0; 3.1 | 1.000 |
| SECONDARY Percentage of Participants Who Achieve Endoscopic Response at Week 52 |
60.0; 75.0; 75.0; 40.0; 100; 15.6 | 0.669 |
| SECONDARY Percentage of Participants Who Achieve Enhanced Endoscopic Response at Week 52 |
40.0; 50.0; 68.8; 30.0; 100; 12.5 | 0.691 |
| SECONDARY Percentage of Participants Who Achieve Endoscopic Improvement at Week 52 |
50.0; 50.0; 68.8; 30.0; 100; 12.5 | 1.000 |
| SECONDARY Percentage of Participants Who Achieve Endoscopic Healing at Week 52 |
15.0; 25.0; 50.0; 0; 0; 9.4 | 0.606 |
| SECONDARY Percentage of Participants Who Achieve Clinical Response Over Time During Extension Phase |
85.0; 100; 100; 80.0; 100; 85.0 | 0.536 |
| SECONDARY Percentage of Participants Who Achieve Enhanced Clinical Response Over Time During Extension Phase |
70.0; 87.5; 100; 70.0; 100; 80.0 | 0.633 |
| SECONDARY Percentage of Participants Who Achieve Enhanced Clinical Response Over Time During Extension Phase Among Participants In Enhanced Clinical Response At Week 16 |
70.0; 100; 100; 66.7; 80.0; 71.4 | 0.155 |
| SECONDARY 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 |
44.4; 16.7; 37.5; 20.0; 55.6; 16.7 | 0.580 |
| SECONDARY Percentage of Participants Taking Corticosteroids at Induction Baseline Who Discontinued Corticosteroid Use and Achieve CDAI < 150 Over Time |
50.0; 50.0; 75.0; 0; 50.0; 50.0 | 1.000 |
| SECONDARY Percentage of Participants Taking Corticosteroids at Induction Baseline Who Discontinued Corticosteroid Use and Achieve Remission At Week 52 |
25.0; 0; 37.5; 0; 0; 0 | 1.000 |
| SECONDARY Percentage of Participants Taking Corticosteroids at Induction Baseline Who Discontinued Corticosteroid Use and Achieve Clinical Remission Over Time |
50.0; 50.0; 50.0; 0; 37.5; 50.0 | 1.000 |
| SECONDARY 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 |
33.3; 50.0; 62.5; 20.0; 50.0; 50.0 | 1.000 |
| SECONDARY Percentage of Participants Taking Corticosteroids at Induction Baseline Who Discontinued Corticosteroid Use and Achieve Endoscopic Remission at Week 52 |
25.0; 0; 50.0; 0; 0; 20.0 | 1.000 |
| SECONDARY Percentage Of Participants Who Achieve CDAI < 150 Over Time During Extension Phase |
65.0; 50.0; 75.0; 50.0; 0; 75.0 | 0.671 |
| SECONDARY Percentage of Participants With Decrease in CDAI ≥ 70 Points From Induction Baseline Over Time During Extension Phase |
80.0; 100; 93.8; 60.0; 100; 85.0 | 0.295 |
| SECONDARY Change From Induction Baseline in Fecal Calprotectin Level Over Time During Extension Phase |
-153.4; -532.0; -2878.6; -3563.7; -194.0; -51.9 | 0.356 |
| SECONDARY Change From Induction Baseline in Hs-CRP Over Time During Extension Phase |
-9.5; -9.4; -20.8; 4.1; -3.1; -6.0 | 0.822 |
| SECONDARY Change From Induction Baseline in IBDQ at Week 52 |
43.9; 56.4; 82.3; 45.3; -5.0; 20.8 | 0.792 |
| SECONDARY Change From Induction Baseline in European Quality of Life (EuroQol) 5 Dimensions Questionnaire (EQ-5D) Index Score at Week 52 |
0.1350; 0.1673; 0.2274; 0.0122; 0.3260; 0.0208 | 0.893 |
| SECONDARY Change From Induction Baseline in EQ-5D VAS at Week 52 |
12.9; 26.9; 34.8; 5.0; 5.0; 12.3 | 0.263 |
| SECONDARY Cross Tabulation of Induction Baseline and Week 52 in Total Number of Extra-Intestinal Manifestations (EIMs) of Crohn's Disease |
85.7; 100; 86.4; 76.0; 73.3; 85.0 | — |
| SECONDARY Percentage of Participants Who Achieve Remission at Week 52 Among Participants With Isolated Ileal Crohn's Disease at Baseline |
50.0; 0; 0; 0; 0; 0 | 1.000 |
| SECONDARY 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 |
66.7; 0; 0; 33.3; 0; 0 | 1.000 |
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
- Diagnosis of Crohn's disease (CD) for at least 90 days.
- Crohn's Disease Activity Index (CDAI) greater than or equal to 220 and less than or equal to 450.
- 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
- Subjects with ulcerative colitis (UC), collagenous colitis or indeterminate colitis.
- Subject who has had surgical bowel resections in the past 6 months or is planning resection.
- Subjects with an ostomy or ileoanal pouch.
- Subject with symptomatic bowel stricture or abdominal or peri-anal abcess.
- Subject who has short bowel syndrome.
- Subject with recurring infections or active Tuberculosis (TB).
Data sourced from ClinicalTrials.gov (NCT02365649). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.