A Maintenance and Long-Term Extension Study of the Efficacy and Safety of Upadacitinib (ABT-494) in Subjects With Crohn's Disease Who Completed the Studies M14-431 or M14-433

Study Description

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Brief Summary:

A multicenter study to evaluate the efficacy and safety of maintenance and long-term treatment administration of upadacitinib, an orally administered Janus kinase 1 inhibitor, in adult participants with Crohn's Disease.

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

Study Design

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Study Type :	Interventional (Clinical Trial)
Estimated Enrollment :	738 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 Maintenance and Long-Term Extension Study of the Efficacy and Safety of Upadacitinib (ABT-494) in Subjects With Crohn's Disease Who Completed the Studies M14-431 or M14-433
Actual Study Start Date :	March 29, 2018
Estimated Primary Completion Date :	January 30, 2019
Estimated Study Completion Date :	March 22, 2023

Arms and Interventions

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Arm	Intervention/treatment
Experimental: Group A - Arm B; This is a maintenance group with 52 weeks which includes participants who achieved clinical response to upadacitinib dose A in studies M14-431 and M14-433 and will receive dose C.	Drug: Upadacitinib; Tablet; Other Name: ABT-494
Experimental: Group B - Arm C; This is a long-term extension group with 240 weeks which includes participants who complete group A.	Drug: Placebo for Upadacitinib; Tablet
Experimental: Group B - Arm A; This is a long-term extension group with 240 weeks which includes participants who complete group A and will receive dose B.	Drug: Upadacitinib; Tablet; Other Name: ABT-494
Experimental: Group B - Arm B; This is a long-term extension group with 240 weeks which includes participants who complete group A and will receive dose C.	Drug: Upadacitinib; Tablet; Other Name: ABT-494
Experimental: Group A - Arm A; This is a maintenance group with 52 weeks which includes participants who achieved clinical response to upadacitinib dose A in studies M14-431 and M14-433 and will receive dose B.	Drug: Upadacitinib; Tablet; Other Name: ABT-494
Experimental: Group A- Arm C; This is a maintenance group with 52 weeks which includes participants who achieved clinical response to upadacitinib dose A in studies M14-431 and M14-433 and will receive placebo.	Drug: Placebo for Upadacitinib; Tablet

Outcome Measures

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Primary Outcome Measures :

1. Proportion of participants with clinical remission [ Time Frame: Week 52 ]
   Clinical remission is defined based on average daily stool frequency (SF) AND average daily abdominal pain (AP) score.
2. Proportion of participants with endoscopic response [ Time Frame: Week 52 ]
   Endoscopic response is defined as decrease in Simple Endoscopic Score for Crohn's Disease (SES-CD) from Baseline.

Secondary Outcome Measures :

1. Proportion of participants with endoscopic remission [ Time Frame: Week 52 ]
   Endoscopic remission is defined per SES-CD.
2. Proportion of participants who discontinue corticosteroid use and achieve clinical remission [ Time Frame: Week 52 ]
   This is assessed in participants taking corticosteroids at Baseline.
3. Proportion of subjects with clinical remission and endoscopic remission [ Time Frame: Week 0 and Week 52 ]
   Clinical remission is defined based on average daily stool frequency (SF) AND average daily abdominal pain (AP) score. Endoscopic remission is defined per SES-CD.
4. Proportion of participants with hospitalizations due to CD [ Time Frame: Week 52 ]
   This is assessed by reviewing participant's hospitalization data.
5. Proportion of participants with >= 50% reduction in draining fistulas [ Time Frame: Week 52 ]
   This is assessed in participants with draining fistulas at Baseline.
6. Proportion of participants who discontinue corticosteroid use [ Time Frame: Week 52 ]
   This is assessed in participants taking corticosteroids at Baseline of induction.
7. Proportion of participants achieving response in Inflammatory Bowel Disease Questionnaire (IBDQ) Bowel Symptom domain [ Time Frame: Week 52 ]
   IBDQ bowel symptom domain response is defined as the increase of IBDQ bowel symptom domain score >= 8
8. Change from Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) [ Time Frame: From Week 0 to Week 52 ]
   The FACIT-F questionnaire was developed to assess fatigue.
9. 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 52 ]
   CDAI remission is defined as CDAI < 150
10. Proportion of participants with clinical remission [ Time Frame: Week 0 and Week 52 ]
    Clinical remission is defined based on average daily stool frequency (SF) AND average daily abdominal pain (AP) score.
11. Proportion of participants with draining fistulas [ Time Frame: Week 52 ]
    This is assessed in participants with draining fistulas at Baseline of induction study.
12. Change from Baseline in Crohn's Symptoms Severity Questionnaire (CSS) [ Time Frame: From Week 0 to Week 52 ]
    The CSS is a self-administered questionnaire that consists of questions about how the participants felt in regards to their Crohn's disease.
13. Proportion of participants with enhanced clinical response [ Time Frame: Week 52 ]
    Enhanced Clinical Response defined as decrease in average daily SF and/or decrease in average daily AP score.

Eligibility Criteria

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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:

For Substudy 1:

• Participant who receive double-blind treatment in Study M14-431 or Study M14-433 and achieve clinical response.
• Participant completes study procedures in the parent study.

For Substudy 2:

• Participant completes Substudy 1
• Participant who receive open-label upadacitinib Dose B in Study M14-431 and achieve clinical response.
• Participant completes study procedures in the parent study/substudy.

Exclusion Criteria:

For Sub-studies 1 and 2:

• Participant is considered by the investigator, for any reason, to be an unsuitable candidate for the study.
• Participant who has a known hypersensitivity to upadacitinib or its excipients, or had an adverse event during Studies M14-431 and M14-433 or Substudy 1 of Study M14-430 that in the investigator's judgment makes the subject unsuitable for this study.
• Participant with any active or chronic recurring infections based on the investigator's assessment that makes the subject an unsuitable candidate for the study. Subjects with ongoing infections undergoing treatment may be enrolled BUT NOT dosed until the infection treatment has been completed and the infection is cured, based on the investigator's assessment.
• Participants with high grade colonic dysplasia or malignancy diagnosed at the endoscopy performed at the final visit of Studies M14-431, M14-433 or Substudy 1 of Study M14-430 (Week 52).

Contacts and Locations

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  Show 434 Study Locations

Sponsors and Collaborators

AbbVie

Investigators

Study Director:	AbbVie Inc.	AbbVie

More Information

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Responsible Party:	AbbVie
ClinicalTrials.gov Identifier:	NCT03345823 History of Changes
Other Study ID Numbers:	M14-430; 2017-001225-41 ( EudraCT Number )
First Posted:	November 17, 2017
Last Update Posted:	November 16, 2018
Last Verified:	November 2018
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); Analytic Code
Time Frame:	Data requests can be submitted at any time and the data will be accessible for 12 months, with possible extensions considered.
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 Sharing Agreement (DSA). For more information on the process, or to submit a request, visit the following link.
URL:	https://www.abbvie.com/our-science/clinical-trials/clinical-trials-data-and-information-sharing/data-and-information-sharing-with-qualified-researchers.html

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; ABT-494; Extension Study; Efficacy	Safety; Crohn's Disease; Maintenance Study

Additional relevant MeSH terms:

Crohn Disease; Inflammatory Bowel Diseases; Gastroenteritis	Gastrointestinal Diseases; Digestive System Diseases; Intestinal Diseases