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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

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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

Tracking Information
First Submitted Date  ICMJE November 15, 2017
First Posted Date  ICMJE November 17, 2017
Results First Submitted Date  ICMJE July 18, 2022
Results First Posted Date  ICMJE August 15, 2022
Last Update Posted Date August 15, 2022
Actual Study Start Date  ICMJE November 29, 2017
Actual Primary Completion Date August 11, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 18, 2022)
  • 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).
  • 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.
  • 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.
Original Primary Outcome Measures  ICMJE
 (submitted: November 15, 2017)
  • Proportion of participants with clinical remission [ Time Frame: Week 12 ]
    Clinical remission is defined based on average daily stool frequency (SF) AND average daily abdominal pain (AP) score.
  • Proportion of participants with endoscopic response [ Time Frame: Week 12 ]
    Endoscopic response is defined as decrease in SES-CD from Baseline.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: July 18, 2022)
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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 ]
  • 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.
Original Secondary Outcome Measures  ICMJE
 (submitted: November 15, 2017)
  • Proportion of participants with clinical remission per Crohn's Disease Activity Index (CDAI) remission in participants with a Baseline CDAI of 220 to 450 [ Time Frame: Week 12 ]
    CDAI remission is defined as CDAI < 150.
  • Proportion of participants with clinical remission [ Time Frame: Week 4 ]
    Clinical remission is defined based on average daily stool frequency (SF) AND average daily abdominal pain (AP) score.
  • Proportion of participants with enhanced clinical response [ Time Frame: Week 2 ]
    Enhanced Clinical Response defined as decrease in average daily SF and/or decrease in average daily AP score.
  • Proportion of participants with endoscopic remission [ Time Frame: Week 12 ]
    Endoscopic remission is defined per SES-CD.
  • Proportion of participants who discontinue corticosteroid use for Crohn's disease (CD) and achieve clinical remission [ Time Frame: Week 12 ]
    This is assessed in participants taking corticosteroids at Baseline.
  • Proportion of participants with >= 50% reduction in draining fistulas [ Time Frame: Week 12 ]
    This is assessed in participants with draining fistulas at Baseline.
  • Change from Baseline in Crohn's Symptoms Severity Questionnaire (CSS) [ Time Frame: From Week 0 to Week 12 ]
    The CSS is a self-administered questionnaire that consists of questions about how the participants felt in regards to their Crohn's disease.
  • Proportion of participants with hospitalizations due to CD [ Time Frame: Week 12 ]
    This is assessed during 12 week double-blind induction period by reviewing participant's hospitalization data.
  • Change from Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) [ Time Frame: From Week 0 to Week 12 ]
    The FACIT-F questionnaire was developed to assess fatigue.
  • Change from Baseline in Short Form 36 (SF-36) [ Time Frame: From Week 0 to Week 12 ]
    The SF-36 questionnaire is a self-administered multi-domain scale with 36 items.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE 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
Official Title  ICMJE 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
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).
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Crohn's Disease
Intervention  ICMJE
  • Drug: Matching Placebo for Upadacitinib
    Matching placebo tablets
  • Drug: Upadacitinib
    Upadacitinib tablets
    Other Names:
    • ABT-494
    • RINVOQ®
Study Arms  ICMJE
  • 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.
    Intervention: Drug: Matching Placebo for Upadacitinib
  • Experimental: Part 1 (Double-blind): Upadacitinib 45 mg
    Participants received upadacitinib 45 mg tablets, orally, QD for 12 weeks during the DB Induction Period.
    Intervention: Drug: Upadacitinib
  • 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.
    Intervention: Drug: Upadacitinib
  • 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.
    Intervention: Drug: Upadacitinib
  • 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.
    Intervention: Drug: Upadacitinib
  • 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.
    Intervention: Drug: Upadacitinib
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: July 18, 2022)
624
Original Estimated Enrollment  ICMJE
 (submitted: November 15, 2017)
855
Actual Study Completion Date  ICMJE August 11, 2021
Actual Primary Completion Date August 11, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 75 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Argentina,   Australia,   Austria,   Belgium,   Bosnia and Herzegovina,   Brazil,   Bulgaria,   Canada,   Chile,   China,   Colombia,   Croatia,   Czechia,   Denmark,   Egypt,   Estonia,   France,   Germany,   Greece,   Hong Kong,   Hungary,   Ireland,   Israel,   Italy,   Japan,   Korea, Republic of,   Latvia,   Lithuania,   Malaysia,   Mexico,   Netherlands,   Poland,   Portugal,   Puerto Rico,   Romania,   Russian Federation,   Serbia,   Singapore,   Slovakia,   Slovenia,   South Africa,   Spain,   Sweden,   Switzerland,   Taiwan,   Turkey,   United Kingdom,   United States
Removed Location Countries American Samoa,   Belarus,   Ukraine
 
Administrative Information
NCT Number  ICMJE NCT03345836
Other Study ID Numbers  ICMJE M14-431
2017-001226-18 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
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
IPD Sharing Statement  ICMJE
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
Supporting Materials: Statistical Analysis Plan (SAP)
Supporting Materials: 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/
Current Responsible Party AbbVie
Original Responsible Party Same as current
Current Study Sponsor  ICMJE AbbVie
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: ABBVIE INC. AbbVie
PRS Account AbbVie
Verification Date July 2022

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP