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
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Active Comparator: Induction Period ABT-494 Twice Daily Medium/High Dose Induction Period ABT-494 Twice Daily Medium/High Dose orally dosed twice a day |
Drug: ABT-494
Oral Dosing
Other Names:
|
| Active Comparator: Extension Phase ABT-494 High Dose Extension Phase ABT-494 High Dose orally dosed twice a day |
Drug: ABT-494
Oral Dosing
Other Names:
|
| Placebo Comparator: Induction Period Placebo Induction Period Placebo orally dosed twice a day |
Drug: Placebo
Oral Dosing
|
| Active Comparator: Induction Period ABT-494 Low Dose Induction Period ABT-494 Low Dose orally dosed twice a day |
Drug: ABT-494
Oral Dosing
Other Names:
|
| Active Comparator: Induction Period ABT-494 Once Daily Medium/High Dose Induction Period ABT-494 Once Daily Medium/High Dose orally dosed once a day |
Drug: ABT-494
Oral Dosing
Other Names:
|
| Active Comparator: Extension Phase ABT-494 Low Dose Extension Phase ABT-494 Low Dose orally dosed twice a day |
Drug: ABT-494
Oral Dosing
Other Names:
|
| Active Comparator: Induction Period ABT-494 High Dose Induction Period ABT-494 High Dose orally dosed twice a day |
Drug: ABT-494
Oral Dosing
Other Names:
|
| Active Comparator: Induction Period ABT-494 Low/Medium Dose Induction Period ABT-494 Low/Medium Dose orally dosed twice a day |
Drug: ABT-494
Oral Dosing
Other Names:
|
| Active Comparator: Extension Phase ABT-494 Medium Dose Extension Phase ABT-494 Medium Dose orally dosed twice a day |
Drug: ABT-494
Oral Dosing
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Percentage of Participants Who Achieve Endoscopic Remission at Week 12/16 [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.)]
Endoscopic remission was determined using Simplified Endoscopic Score for Crohn's Disease (SES-CD). SES-CD subscores assess the following: presence and size of ulcers in 5 visualized bowel segments; extent of ulcerated surface in 5 visualized bowel segments; extent of affected surface in 5 visualized bowel segments; presence and type of narrowings in 5 visualized bowel segments. Subscores range from 0 to 15, and are summed for a total SES-CD score ranging from 0 to 56; higher scores indicate greater severity of mucosal inflammation. Endoscopic remission: SES-CD ≤ 4 and at least 2-point reduction versus Baseline and no subscore > 1 in any individual variable. Modified intention to Treat (mITT) Population: all randomized subjects who took at least 1 dose of study drug in the Induction Period. Non-responder imputation.
- Percentage of Participants Who Achieve Clinical Remission at Week 16 [Week 16]
Clinical remission: average daily stool frequency ≤ 1.5 and not worse than Baseline AND average daily abdominal pain ≤ 1.0 and not worse than Baseline. The very soft/liquid stool frequency and abdominal pain scores at a visit were the average of the daily values reported during the 7 usable days preceding the scheduled assessment visit. Abdominal Pain was rated on a 4-point scale from 0 (none) to 3 (severe). mITT Population: all randomized subjects who took at least 1 dose of study drug in the Induction Period. Non-responder imputation.
Secondary Outcome Measures
- Percentage of Subjects Who Achieve Crohn's Disease Activity Index (CDAI) < 150 at Week 16 [Week 16]
CDAI is used to quantify the signs and symptoms of subjects with Crohn's disease. The score includes the frequency of stools, abdominal pain and general well-being as well as the presence of complications, use of antidiarrheals, presence of abdominal mass, hematocrit and weight. CDAI generally ranges from 0 to 600 where higher scores indicate more severe disease. A score below 150 indicates remission. mITT Population: all randomized subjects who took at least 1 dose of study drug in the Induction Period. Non-responder imputation.
- Percentage of Participants With a Decrease in CDAI ≥ 70 Points From Baseline at Week 16 [Week 16]
CDAI is used to quantify the signs and symptoms of subjects with Crohn's disease. The score includes the frequency of stools, abdominal pain and general well-being as well as the presence of complications, use of antidiarrheals, presence of abdominal mass, hematocrit and weight. CDAI generally ranges from 0 to 600 where higher scores indicate more severe disease. A 70-point decrease in the CDAI index refers to improvement in the disease activity from Baseline. mITT Population: all randomized subjects who took at least 1 dose of study drug in the Induction Period. Non-responder imputation.
- Percentage of Participants Who Achieve Clinical Remission at Week 12 [Week 12]
Clinical remission: average daily stool frequency ≤ 1.5 and not worse than Baseline AND average daily abdominal pain ≤ 1.0 and not worse than Baseline. The very soft/liquid stool frequency and abdominal pain scores at a visit were the average of the daily values reported during the 7 usable days preceding the scheduled assessment visit. Abdominal Pain was rated on a 4-point scale from 0 (none) to 3 (severe). mITT Population: all randomized subjects who took at least 1 dose of study drug in the Induction Period. Non-responder imputation.
- Percentage of Participants Who Achieve Remission at Week 16 [Week 16]
Remission is defined as endoscopic remission at Week 12/16 AND clinical remission at Week 16. Endoscopic remission: SES-CD ≤ 4 and at least 2-point reduction versus Baseline and no subscore > 1 in any individual variable. Clinical remission: average daily stool frequency ≤ 1.5 and not worse than Baseline AND average daily abdominal pain ≤ 1.0 and not worse than Baseline. The very soft/liquid stool frequency and abdominal pain scores at a visit were the average of the daily values reported during the 7 usable days preceding the scheduled assessment visit. Abdominal Pain was rated on a 4-point scale from 0 (none) to 3 (severe). Details of the SES-CD scale are provided in the description of the first primary endpoint. mITT Population: all randomized subjects who took at least 1 dose of study drug in the Induction Period. Non-responder imputation.
- Percentage of Participants Who Achieve Response at Week 16 [Week 16]
Response is defined as endoscopic response at Week 12/16 AND clinical response at Week 16. Endoscopic response: SES-CD at least 25% reduction from Baseline. Clinical response: average daily stool frequency at least 30% reduction from Baseline and average daily abdominal pain not worse than Baseline OR average daily abdominal pain at least 30% reduction from Baseline and average daily stool frequency not worse than Baseline. The very soft/liquid stool frequency and abdominal pain scores at a visit were the average of the daily values reported during the 7 usable days preceding the scheduled assessment visit. Abdominal Pain was rated on a 4-point scale from 0 (none) to 3 (severe). Details of the SES-CD scale are provided in the description of the first primary endpoint. mITT Population: all randomized subjects who took at least 1 dose of study drug in the Induction Period. Non-responder imputation.
- Percentage of Participants With Endoscopic Response at Week 12/16 [Up to Week 16. (At Baseline, patients 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.)]
Endoscopic response: SES-CD at least 25% reduction from Baseline. Details of the SES-CD scale are provided in the description of the first primary endpoint. mITT Population: all randomized subjects who took at least 1 dose of study drug in the Induction Period. Non-responder imputation.
- Percentage of Participants Who Achieve Clinical Response at Week 16 [Week 16]
Clinical response: average daily stool frequency at least 30% reduction from Baseline and average daily abdominal pain not worse than Baseline OR average daily abdominal pain at least 30% reduction from Baseline and average daily stool frequency not worse than Baseline. The very soft/liquid stool frequency and abdominal pain scores at a visit were the average of the daily values reported during the 7 usable days preceding the scheduled assessment visit. Abdominal Pain was rated on a 4-point scale from 0 (none) to 3 (severe). mITT Population: all randomized subjects who took at least 1 dose of study drug in the Induction Period. Non-responder imputation.
- Percentage of Subjects With an Average Daily Stool Frequency ≥ 2.5 AND Average Daily Abdominal Pain ≥ 2.0 at Baseline Who Achieve Clinical Remission at Week 16 [Week 16]
Clinical remission: average daily stool frequency ≤ 1.5 and not worse than Baseline AND average daily abdominal pain ≤ 1.0 and not worse than Baseline. The very soft/liquid stool frequency and abdominal pain scores at a visit were the average of the daily values reported during the 7 usable days preceding the scheduled assessment visit. Abdominal Pain was rated on a 4-point scale from 0 (none) to 3 (severe). mITT Population: all randomized subjects who took at least 1 dose of study drug in the Induction Period. Includes only mITT subjects with an average daily stool frequency ≥ 2.5 AND average daily abdominal pain ≥ 2.0 at Baseline. Non-responder imputation.
- Percentage of Participants Taking Corticosteroids at Baseline Who Discontinued Corticosteroid Use and Achieve CDAI < 150 at Week 16 [Week 16]
CDAI is used to quantify the signs and symptoms of subjects with Crohn's disease. The score includes the frequency of stools, abdominal pain and general well-being as well as the presence of complications, use of antidiarrheals, presence of abdominal mass, hematocrit and weight. CDAI generally ranges from 0 to 600 where higher scores indicate more severe disease. A score below 150 indicates remission. mITT Population: all randomized subjects who took at least 1 dose of study drug in the Induction Period. Includes only subjects taking corticosteroids at Baseline. Non-responder imputation.
- Percentage of Participants Taking Corticosteroids at Baseline Who Discontinued Corticosteroid Use and Achieve Remission at Week 12/16 and Clinical Remission at Week 16 [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.)]
Remission is defined as endoscopic remission at Week 12/16 AND clinical remission at Week 16. Endoscopic remission: SES-CD ≤ 4 and at least 2-point reduction versus Baseline and no subscore > 1 in any individual variable. Clinical remission: average daily stool frequency ≤ 1.5 and not worse than Baseline AND average daily abdominal pain ≤ 1.0 and not worse than Baseline. The very soft/liquid stool frequency and abdominal pain scores at a visit were the average of the daily values reported during the 7 usable days preceding the scheduled assessment visit. Abdominal Pain was rated on a 4-point scale from 0 (none) to 3 (severe). Details of the SES-CD scale are provided in the description of the first primary endpoint. mITT Population: all randomized subjects who took at least 1 dose of study drug in the Induction Period. Includes only subjects taking corticosteroids at Baseline. Non-responder imputation.
- Percentage of Subjects Taking Corticosteroids at Baseline Who Discontinued Corticosteroid Use and Achieve Clinical Remission at Week 16 [Week 16]
Clinical remission: average daily stool frequency ≤ 1.5 and not worse than Baseline AND average daily abdominal pain ≤ 1.0 and not worse than Baseline. The very soft/liquid stool frequency and abdominal pain scores at a visit were the average of the daily values reported during the 7 usable days preceding the scheduled assessment visit. Abdominal Pain was rated on a 4-point scale from 0 (none) to 3 (severe). mITT Population: all randomized subjects who took at least 1 dose of study drug in the Induction Period. Includes only subjects taking corticosteroids at Baseline. Non-responder imputation.
- Percentage of Subjects Taking Corticosteroids at Baseline Who Discontinued Corticosteroid Use and Achieve Endoscopic Remission at Week 12/16 [Up to Week 16. (At Baseline, patients 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.)]
Endoscopic remission: SES-CD ≤ 4 and at least 2-point reduction versus Baseline and no subscore > 1 in any individual variable. Details of the SES-CD scale are provided in the description of the first primary endpoint. mITT Population: all randomized subjects who took at least 1 dose of study drug in the Induction Period. Includes only subjects taking corticosteroids at Baseline. Non-responder imputation.
- Change from Baseline in Fecal Calprotectin Level Over Time During the Induction Phase [Baseline, Week 4, Week 16]
mITT Population: all randomized subjects who took at least 1 dose of study drug in the Induction Period. Includes only subjects with an assessment at Baseline and Week 16. n=subjects with an assessment at given time point.
- Change from Baseline in High-Sensitivity C-Reactive Protein (hs-CRP) at Week 16 [Baseline, Week 16]
mITT Population: all randomized subjects who took at least 1 dose of study drug in the Induction Period. Includes only subjects with an assessment at Baseline and Week 16.
- Change From Baseline in Inflammatory Bowel Disease Questionnaire (IBDQ) Over Time During the Induction Phase [Baseline, Week 8, Week 16]
The IBDQ is a disease-specific instrument composed of 32 Likert-scaled items. The total score ranges from 32 to 224 using the 7-point response options, with higher scores indicating better health-related quality of life. The IBDQ scale contains 4 component subscales: bowel symptoms, systemic symptoms, emotional function, and social function. Each subscale can be computed with total scores ranging from 10 to 70, 5 to 35, 12 to 84, and 5 to 35, respectively. mITT Population: all randomized subjects who took at least 1 dose of study drug in the Induction Period. Includes only subjects with an assessment at Baseline and Week 16. n=number of subjects with an assessment at given time point.
- Percentage of Subjects With Isolated Ileal Crohn's Disease at Baseline Who Achieve Remission at Week 16 [Week 16]
Remission is defined as endoscopic remission AND clinical remission. Endoscopic remission: SES-CD ≤ 4 and at least 2-point reduction versus Baseline and no subscore > 1 in any individual variable. Clinical remission: average daily stool frequency ≤ 1.5 and not worse than Baseline AND average daily abdominal pain ≤ 1.0 and not worse than Baseline. The very soft/liquid stool frequency and abdominal pain scores at a visit were the average of the daily values reported during the 7 usable days preceding the scheduled assessment visit. Abdominal Pain was rated on a 4-point scale from 0 (none) to 3 (severe). Details of the SES-CD scale are provided in the description of the first primary endpoint. mITT Population: all randomized subjects who took at least 1 dose of study drug in the Induction Period. Only mITT subjects with isolated ileal Crohn's disease at Baseline are included. Non-responder imputation.
Eligibility Criteria
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.
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Subject inadequately responded to or experience 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.
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Subject who has had surgical bowel resections in the past 6 months or is planning resection.
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Subjects with an ostomy or ileoanal pouch.
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Subject with symptomatic bowel stricture or abdominal or peri-anal abcess.
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Subject who has short bowel syndrome.
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Subject with recurring infections or active Tuberculosis (TB).
Contacts and Locations
Locations
No locations specified.Sponsors and Collaborators
- AbbVie
Investigators
- Study Director: AbbVie Inc., AbbVie
Study Documents (Full-Text)
None provided.More Information
Publications
- M13-740
- 2014-003240-12