Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02365649
Recruitment Status : Completed
First Posted : February 19, 2015
Last Update Posted : August 3, 2021
Sponsor:
Information provided by (Responsible Party):
AbbVie

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
Crohn's Disease Drug: Placebo Drug: ABT-494 Phase 2

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 220 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: 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
Actual Study Start Date : March 17, 2015
Actual Primary Completion Date : November 25, 2016
Actual Study Completion Date : August 3, 2017

Resource links provided by the National Library of Medicine


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 Name: Upadacitinib

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 Name: Upadacitinib

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 Name: Upadacitinib

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 Name: Upadacitinib

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 Name: Upadacitinib

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 Name: Upadacitinib

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 Name: Upadacitinib

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 Name: Upadacitinib




Primary Outcome Measures :
  1. Percentage of Participants Who Achieve Endoscopic Remission at Week 12/16 [ Time Frame: 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.


  2. Percentage of Participants Who Achieve Clinical Remission at Week 16 [ Time Frame: 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 :
  1. Percentage of Subjects Who Achieve Crohn's Disease Activity Index (CDAI) < 150 at Week 16 [ Time Frame: 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.


  2. Percentage of Participants With a Decrease in CDAI ≥ 70 Points From Baseline at Week 16 [ Time Frame: 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.


  3. Percentage of Participants Who Achieve Clinical Remission at Week 12 [ Time Frame: 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.


  4. Percentage of Participants Who Achieve Remission at Week 16 [ Time Frame: 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.


  5. Percentage of Participants Who Achieve Response at Week 16 [ Time Frame: 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.


  6. Percentage of Participants With Endoscopic Response at Week 12/16 [ Time Frame: 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.

  7. Percentage of Participants Who Achieve Clinical Response at Week 16 [ Time Frame: 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.


  8. 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 [ Time Frame: 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.


  9. Percentage of Participants Taking Corticosteroids at Baseline Who Discontinued Corticosteroid Use and Achieve CDAI < 150 at Week 16 [ Time Frame: 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.


  10. Percentage of Participants Taking Corticosteroids at Baseline Who Discontinued Corticosteroid Use and Achieve Remission at Week 12/16 and Clinical Remission at Week 16 [ Time Frame: 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.


  11. Percentage of Subjects Taking Corticosteroids at Baseline Who Discontinued Corticosteroid Use and Achieve Clinical Remission at Week 16 [ Time Frame: 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.


  12. Percentage of Subjects Taking Corticosteroids at Baseline Who Discontinued Corticosteroid Use and Achieve Endoscopic Remission at Week 12/16 [ Time Frame: 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.


  13. Change from Baseline in Fecal Calprotectin Level Over Time During the Induction Phase [ Time Frame: 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.


  14. Change from Baseline in High-Sensitivity C-Reactive Protein (hs-CRP) at Week 16 [ Time Frame: 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.


  15. Change From Baseline in Inflammatory Bowel Disease Questionnaire (IBDQ) Over Time During the Induction Phase [ Time Frame: 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.


  16. Percentage of Subjects With Isolated Ileal Crohn's Disease at Baseline Who Achieve Remission at Week 16 [ Time Frame: 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.




Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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 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:

  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).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02365649


Sponsors and Collaborators
AbbVie
Investigators
Layout table for investigator information
Study Director: AbbVie Inc. AbbVie
Publications:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: AbbVie
ClinicalTrials.gov Identifier: NCT02365649    
Other Study ID Numbers: M13-740
2014-003240-12 ( EudraCT Number )
First Posted: February 19, 2015    Key Record Dates
Last Update Posted: August 3, 2021
Last Verified: July 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Keywords provided by AbbVie:
Crohn's Disease
Additional relevant MeSH terms:
Layout table for MeSH terms
Crohn Disease
Inflammatory Bowel Diseases
Gastroenteritis
Gastrointestinal Diseases
Digestive System Diseases
Intestinal Diseases
Upadacitinib
Janus Kinase Inhibitors
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antirheumatic Agents