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A Study of the Efficacy and Safety of Upadacitinib (ABT-494) in Participants With Moderately to Severely Active Crohn's Disease Who Have Inadequately Responded to or Are Intolerant to Biologic 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: NCT03345836
Recruitment Status : Completed
First Posted : November 17, 2017
Results First Posted : August 15, 2022
Last Update Posted : August 15, 2022
Sponsor:
Information provided by (Responsible Party):
AbbVie

Study Description
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Brief Summary:
The objective of this study is to evaluate the efficacy and safety of upadacitinib compared to placebo as induction therapy in participants with moderately and severely active Crohn's disease (CD).

Condition or disease Intervention/treatment Phase
Crohn's Disease Drug: Matching Placebo for Upadacitinib Drug: Upadacitinib Phase 3

Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 624 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 Induction Study of the Efficacy and Safety of Upadacitinib (ABT-494) in Subjects With Moderately to Severely Active Crohn's Disease Who Have Inadequately Responded to or Are Intolerant to Biologic Therapy
Actual Study Start Date : November 29, 2017
Actual Primary Completion Date : August 11, 2021
Actual Study Completion Date : August 11, 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Crohn's Disease

Arms and Interventions
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Arm Intervention/treatment
Placebo Comparator: Part 1 (Double-blind): Placebo
Participants received upadacitinib matching placebo tablets, orally, once daily (QD) for 12 weeks during the Double-blind (DB) Induction Period.
 Drug: Matching Placebo for Upadacitinib
Matching placebo tablets
Experimental: Part 1 (Double-blind): Upadacitinib 45 mg
Participants received upadacitinib 45 mg tablets, orally, QD for 12 weeks during the DB Induction Period.
 Drug: Upadacitinib
Upadacitinib tablets
Other Names:
  • ABT-494
  • RINVOQ®
Experimental: Part 2 (Open-label): Upadacitinib 45 mg
Participants received upadacitinib 45 mg tablets, orally, QD for 12 weeks during the Open-label (OL) Induction Period.
 Drug: Upadacitinib
Upadacitinib tablets
Other Names:
  • ABT-494
  • RINVOQ®
Experimental: Part 3 (Extended Treatment DB): Upadacitinib 45 mg From Part 1 DB Placebo
Participants received upadacitinib 45 mg tablets, orally, QD for 12 weeks (until Week 24) during the Extended Treatment (ET) Period. Participants who received placebo in Part 1 and did not achieve clinical response at Week 12 were included in this group.
 Drug: Upadacitinib
Upadacitinib tablets
Other Names:
  • ABT-494
  • RINVOQ®
Experimental: Part 3 (Extended Treatment DB): Upadacitinib 30 mg From Part 1 DB Upadacitinib 45 mg
Participants received upadacitinib 30 mg tablets, orally, QD for 12 weeks (until Week 24) during the ET Period. Participants who received DB upadacitinib 45 mg in Part 1 and did not achieve clinical response at Week 12 were included in this group.
 Drug: Upadacitinib
Upadacitinib tablets
Other Names:
  • ABT-494
  • RINVOQ®
Experimental: Part 3 (Extended Treatment OL): Upadacitinib 30 mg From Part 2 OL Upadacitinib 45 mg
Participants received upadacitinib 30 mg tablets, orally, QD for 12 weeks (until Week 24) during the ET Period. Participants who received OL upadacitinib 45 mg during Part 2 and did not achieve clinical response at Week 12 were included in this group.
 Drug: Upadacitinib
Upadacitinib tablets
Other Names:
  • ABT-494
  • RINVOQ®


Outcome Measures
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Primary Outcome Measures :
  1. Percentage of Participants With Clinical Remission Per Crohn's Disease Activity Index (CDAI) at Week 12 [ Time Frame: Week 12 ]
    The CDAI was used to evaluate the activity of Crohn's disease. Clinical remission per CDAI is defined as CDAI <150. The CDAI is calculated on the basis of a one-week evaluation of 8 items: frequency of liquid or very soft stool, abdominal pain, complications of Crohn's disease (e.g., uveitis, arthritis, fistula, and abscess), abdominal mass, hematocrit, body weight, use of antidiarrheals, and general condition. Total score ranges from 0 to about 600. Higher CDAI scores indicate more severe disease. CDAI scores below 150 represent remission and scores over 450 represent very severe Crohn's disease. Results were based on non-responder imputation incorporating multiple imputation to handle missing data due to COVID-19 (NRI-C).

  2. Percentage of Participants With Endoscopic Response at Week 12 [ Time Frame: Baseline to Week 12 ]
    Endoscopic response was defined as greater than 50% decrease in Simple Endoscopic Score for Crohn's Disease (SES-CD) from Baseline of the induction study (or for participants with an SES-CD of 4 at Baseline of the induction study, at least a 2-point reduction from Baseline), as scored by Central Reviewer. SES-CD is calculated based on the sum of individual segment values for four endoscopic variables (presence and size of ulcers, ulcerated surface, affected surface and presence of narrowing). Each variable in each segment is scored 0 to 3 resulting in SES-CD values ranging from 0 to 56 with higher scores indicating more severe disease. Results were based on NRI-C.

  3. Number of Participants With Adverse Events [ Time Frame: From first dose of study drug until 30 days following last dose of study drug (up to approximately 28 weeks) ]
    An adverse event (AE) is defined as any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not the event is considered causally related to the use of the product.


Secondary Outcome Measures :
  1. Percentage of Participants With Clinical Remission Per Patient-Reported Outcomes (PROs) at Week 12 [ Time Frame: Baseline to Week 12 ]
    Clinical remission per PROs was defined as average daily very soft or liquid stool frequency (SF) ≤2.8 and average daily abdominal pain (AP) score ≤1.0 and both not greater than Baseline. The number of soft or liquid stools and abdominal pain rated on a scale of 0=none to 3=severe were recorded in an electronic diary. Results were based on NRI-C.

  2. Percentage of Participants With Endoscopic Remission at Week 12 [ Time Frame: Baseline to Week 12 ]
    Endoscopic remission was defined per SES-CD. SES-CD ≤4 and at least 2-point reduction from Baseline and no subscore >1 in any individual variable, as scored by Central Reviewer. SES-CD is calculated based on the sum of individual segment values for four endoscopic variables (presence and size of ulcers, ulcerated surface, affected surface and presence of narrowing). Each variable in each segment is scored 0 to 3 resulting in SES-CD values ranging from 0 to 56 with higher scores indicating more severe disease. Results were based on NRI-C.

  3. Percentage of Participants Who Discontinued Corticosteroid Use for Crohn's Disease (CD) and Achieved Clinical Remission Per CDAI at Week 12, in Participants Taking Corticosteroids at Baseline [ Time Frame: Week 12 ]
    As prespecified in the protocol, this outcome measure was planned to be assessed in participants taking corticosteroids at Baseline. Clinical remission per CDAI: CDAI <150. The CDAI is used to evaluate the activity of Crohn's disease. The CDAI is calculated on the basis of a one-week evaluation of 8 items: frequency of liquid or very soft stool, abdominal pain, complications of Crohn's disease (e.g., uveitis, arthritis, fistula, and abscess), abdominal mass, hematocrit, body weight, use of antidiarrheals, and general condition. Total score ranges from 0 to about 600. Higher CDAI scores indicate more severe disease. CDAI scores below 150 represent remission and scores over 450 represent very severe Crohn's disease. Results were based on NRI-C.

  4. Change From Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Total Score at Week 12 [ Time Frame: Baseline and Week 12 ]
    The FACIT-F questionnaire was developed to assess fatigue associated with anemia. It consists of 13 fatigue-related questions. The responses to the 13 items on the FACIT-F questionnaire are each measured on a 5-point Likert scale. The responses to the answers are the following: 0= not at all; 1= a little bit; 2= somewhat; 3= quite a bit; 4=very much. Thus, the total score ranges from 0 to 52. High scores represent less fatigue. A positive change from Baseline indicates improvement.

  5. Change From Baseline in Inflammatory Bowel Disease Questionnaire (IBDQ) Total Score at Week 12 [ Time Frame: Baseline and Week 12 ]
    The IBDQ is a disease-specific instrument composed of 32 Likert-scaled items. The IBDQ scale contains 4 component subscales: bowel symptoms (10 items), systemic symptoms (5 items), emotional function (12 items), and social function(5 items). Each item is scored on a 7-point scale where: 1=worst to 7= best. The total score ranges from 32 to 224, with higher scores indicating better health-related quality of life. A positive change from Baseline indicates improvement.

  6. Percentage of Participants Achieving Clinical Response 100 (CR-100) at Week 2 [ Time Frame: Baseline to Week 2 ]
    CR-100 is defined as a decrease of at least 100 points in CDAI from Baseline at Week 2. The CDAI is used to evaluate the activity of Crohn's disease. The CDAI is calculated on the basis of a one-week evaluation of 8 items: frequency of liquid or very soft stool, abdominal pain, complications of Crohn's disease (e.g., uveitis, arthritis, fistula, and abscess), abdominal mass, hematocrit, body weight, use of antidiarrheals, and general condition. Total score ranges from 0 to about 600. Higher CDAI scores indicate more severe disease. CDAI scores below 150 represent remission and scores over 450 represent very severe Crohn's disease. Results were based on NRI-C.

  7. Percentage of Participants Achieving Clinical Response 100 (CR-100) at Week 12 [ Time Frame: Baseline to Week 12 ]
    CR-100 is defined as a decrease of at least 100 points in CDAI from Baseline at Week 12. The CDAI is used to evaluate the activity of Crohn's disease. The CDAI is calculated on the basis of a one-week evaluation of 8 items: frequency of liquid or very soft stool, abdominal pain, complications of Crohn's disease (e.g., uveitis, arthritis, fistula, and abscess), abdominal mass, hematocrit, body weight, use of antidiarrheals, and general condition. Total score ranges from 0 to about 600. Higher CDAI scores indicate more severe disease. CDAI scores below 150 represent remission and scores over 450 represent very severe Crohn's disease. Results were based on NRI-C.

  8. Percentage of Participants With Clinical Remission Per Crohn's Disease Activity Index (CDAI) at Week 4 [ Time Frame: Week 4 ]
    The CDAI was used to evaluate the activity of Crohn's disease. Clinical remission per CDAI is defined as CDAI <150. The CDAI is calculated on the basis of a one-week evaluation of 8 items: frequency of liquid or very soft stool, abdominal pain, complications of Crohn's disease (e.g., uveitis, arthritis, fistula, and abscess), abdominal mass, hematocrit, body weight, use of antidiarrheals, and general condition. Total score ranges from 0 to 600. Higher CDAI scores indicate more severe disease. CDAI scores below 150 represent remission and scores over 450 represent very severe Crohn's disease. Results were based on NRI-C.

  9. Percentage of Participants With Hospitalizations Due to Crohn's Disease (CD) During Part 1 (12-week Double-blind Induction Period) [ Time Frame: Up to Week 12 in Part 1: Double-blind Induction Period ]
  10. Percentage of Participants With Resolution of Extra-Intestinal Manifestations (EIMs) at Week 12, in Participants With EIMs at Baseline [ Time Frame: Week 12 ]
    EIMs are defined as manifestations of Crohn's disease in areas of the body other than the digestive tract, including eyes, skin, joints, mouth, and liver. Results were based on NRI-C.


Eligibility Criteria
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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.


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

Inclusion Criteria:

  • Confirmed diagnosis of CD for at least 3 months prior to Baseline.
  • Confirmed diagnosis of moderate to severe CD as assessed by stool frequency (SF), abdominal pain (AP) score.
  • Evidence of mucosal inflammation based on the Simplified Endoscopic Score for Crohn's disease (SES-CD) on an endoscopy confirmed by a central reader.
  • Demonstrated an inadequate response or intolerance to any biologic therapy for infliximab, adalimumab, certolizumab pegol, vedolizumab, and ustekinumab.
  • If female, participant must meet the contraception recommendations.

Exclusion Criteria:

  • Participant with a current diagnosis of ulcerative colitis or indeterminate colitis.
  • Participant not on stable doses of CD related antibiotics, oral aminosalicylates, corticosteroids or methotrexate (MTX).
  • Participant with the following ongoing known complications of CD: abscess (abdominal or peri-anal), symptomatic bowel strictures, fulminant colitis, toxic megacolon, or any other manifestation that might require surgery while enrolled in the study.
  • Participant with ostomy or ileoanal pouch.
  • Participant diagnosed with conditions that could interfere with drug absorption including but not limited to short gut or short bowel syndrome.
  • Screening laboratory and other protocol pre-specified analyses show abnormal results.
Contacts and Locations
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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): NCT03345836


Locations
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Sponsors and Collaborators
AbbVie
Investigators
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Study Director: ABBVIE INC. AbbVie
  Study Documents (Full-Text)

Documents provided by AbbVie:
Study Protocol  [PDF] March 5, 2021
Statistical Analysis Plan  [PDF] November 15, 2021

More Information
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Additional Information:

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Responsible Party: AbbVie
ClinicalTrials.gov Identifier: NCT03345836    
Other Study ID Numbers: M14-431
2017-001226-18 ( EudraCT Number )
First Posted: November 17, 2017    Key Record Dates
Results First Posted: August 15, 2022
Last Update Posted: August 15, 2022
Last Verified: July 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: AbbVie is committed to responsible data sharing regarding the clinical trials we sponsor. This includes access to anonymized, individual and trial-level data (analysis data sets), as well as other information (e.g., protocols and clinical study reports), as long as the trials are not part of an ongoing or planned regulatory submission. This includes requests for clinical trial data for unlicensed products and indications.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Clinical Study Report (CSR)
Time Frame: For details on when studies are available for sharing, please refer to the link below.
Access Criteria: Access to this clinical trial data can be requested by any qualified researchers who engage in rigorous, independent scientific research, and will be provided following review and approval of a research proposal and Statistical Analysis Plan (SAP) and execution of a Data Use Agreement (DUA). For more information on the process, or to submit a request, visit the following link.
URL: https://vivli.org/ourmember/abbvie/

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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:
Upadacitinib
Crohn's Disease
Efficacy
Safety
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