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

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: NCT03345823
Recruitment Status : Active, not recruiting
First Posted : November 17, 2017
Last Update Posted : May 18, 2023
Sponsor:
Information provided by (Responsible Party):
AbbVie

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 : 747 participants
Allocation: Randomized
Intervention Model: Sequential 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 21, 2018
Estimated Primary Completion Date : September 3, 2027
Estimated Study Completion Date : September 3, 2027

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
Experimental: Substudy 1: Cohort 1 Upadacitinib Dose A
This is a maintenance group which includes participants who achieved clinical response to upadacitinib in studies M14-431 and M14-433 and will receive upadacitinib dose A for 52 weeks.
 Drug: Upadacitinib
Oral; Tablet
Other Names:
  • ABT-494
  • RINVOQ
Experimental: Substudy 1: Cohort 1 Upadacitinib Dose B
This is a maintenance group which includes participants who achieved clinical response to upadacitinib in studies M14-431 and M14-433 and will receive upadacitinib dose B for 52 weeks.
 Drug: Upadacitinib
Oral; Tablet
Other Names:
  • ABT-494
  • RINVOQ
Experimental: Substudy 1: Cohort 1 Placebo
This is a maintenance group which includes participants who achieved clinical response to upadacitinib in studies M14-431 and M14-433 and will receive placebo for 52 weeks.
 Drug: Placebo for Upadacitinib
Oral; Tablet
Experimental: Substudy 1: Cohort 2 Placebo
This is a maintenance group which includes participants who received double-blind placebo in studies M14-431 and M14-433 and achieved clinical response will continue to receive blinded placebo for 52 Weeks.
 Drug: Placebo for Upadacitinib
Oral; Tablet
Experimental: Substudy 1: Cohort 3 Upadacitinib Dose B
This is a maintenance group which includes participants who achieved clinical response to upadacitinib from the extended treatment period of studies M14-431 and M14-433 and will receive upadacitinib Dose B for 52 Weeks.
 Drug: Upadacitinib
Oral; Tablet
Other Names:
  • ABT-494
  • RINVOQ
Experimental: Substudy 2: Cohort 4 Upadacitinib Dose B
This is a long-term extension group which includes participants who achieved clinical response in the open-label extended treatment period of study M14-431 and will receive upadacitinib dose B for 240 weeks.
 Drug: Upadacitinib
Oral; Tablet
Other Names:
  • ABT-494
  • RINVOQ
Experimental: Substudy 2: Cohort 5 Upadacitinib Dose A
This is a long-term extension group which includes participants who complete Substudy 1 and will receive upadacitinib dose A for 240 weeks.
 Drug: Upadacitinib
Oral; Tablet
Other Names:
  • ABT-494
  • RINVOQ
Experimental: Substudy 2: Cohort 5 Upadacitinib Dose B
This is a long-term extension group which includes participants who complete Substudy 1 and will receive upadacitinib dose B for 240 weeks.
 Drug: Upadacitinib
Oral; Tablet
Other Names:
  • ABT-494
  • RINVOQ
Experimental: Substudy 2: Cohort 5 Placebo
This is a long-term extension group which includes participants who complete Substudy 1 and will receive placebo for 240 weeks.
 Drug: Placebo for Upadacitinib
Oral; Tablet
Experimental: Substudy 3: Cohort 6 Upadacitinib Dose A
This is the dose optimization group which includes participants from Substudy 2 who meet the criteria of stable remission will receive open-label upadacitinib dose A for up to 48 weeks.
 Drug: Upadacitinib
Oral; Tablet
Other Names:
  • ABT-494
  • RINVOQ


Outcome Measures
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Primary Outcome Measures :
  1. Sub-Study 1: Percentage of Participants with Clinical Remission per Crohn's Disease Activity Index (CDAI) [ Time Frame: Week 52 ]
    Clinical remission per CDAI is defined as CDAI <150.

  2. Sub-Study 1: Percentage 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.

  3. Number of Participants with Adverse Events [ Time Frame: Through Week 240 ]
    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. The investigator assessed the relationship of each event to the use of study drug as either probably related, possibly related, probably not related or not related. A serious adverse event (SAE) is an event that results in death, is life-threatening, requires or prolongs hospitalization, results in a congenital anomaly, persistent or significant disability/incapacity or is an important medical event that, based on medical judgment, may jeopardize the participant and may require medical or surgical intervention to prevent any of the outcomes listed above. For more details on adverse events please see the Adverse Event section.


Secondary Outcome Measures :
  1. Sub-Study 1: Percentage of Participants with Clinical Remission per Patient-Reported Outcomes (PROs) [ Time Frame: Week 52 ]
    Clinical remission is defined based on average daily stool frequency (SF) AND average daily abdominal pain (AP) score.

  2. Sub-Study 1: Percentage of Participants Achieving Clinical Response 100 (CR-100) [ Time Frame: Week 52 ]
    Decrease of at least 100 points in CDAI from Baseline.

  3. Sub-Study 1: Percentage of Participants with Endoscopic Remission [ Time Frame: Week 52 ]
    Endoscopic remission is defined per Simplified Endoscopic Score for Crohn's Disease (SES-CD).

  4. Sub-Study 1: Percentage of Participants without Corticosteroid use for Crohn's Disease Among All Participants [ Time Frame: Week 52 ]
    This is assessed in participants not taking corticosteroids at least 90 days prior to Week 52 and achieved clinical remission per CDAI. Clinical remission is defined as CDAI <150.

  5. Sub-Study 1: Percentage of Participants with Clinical Remission per CDAI and Endoscopic Remission [ Time Frame: Week 52 ]
    Clinical remission per CDAI is defined as CDAI <150. Endoscopic remission is defined per SES-CD.

  6. Sub-Study 1: Percentage of Participants with Clinical Remission per CDAI [ Time Frame: Through Week 52 ]
    Clinical remission per CDAI is defined as CDAI <150 (as measured by the percentage of participants with clinical remission at Week 52 among those with clinical remission at Week 0).

  7. Sub-Study 1: Percentage of Participants who Discontinue Corticosteroid Use for Crohn's Disease at Least 90 Days Prior to Week 52 and Achieve Clinical Remission, in Participants Taking Corticosteroids at Baseline. [ Time Frame: Week 52 ]
    This is assessed in participants taking corticosteroids at Baseline. Clinical remission is defined based on average daily stool frequency (SF) AND average daily abdominal pain (AP) score.

  8. Sub-Study 1: Change in Inflammatory Bowel Disease Questionnaire (IBDQ) [ Time Frame: Baseline (Week 0) to Week 52 ]
    The IBDQ is used to assess the quality of life of patients with inflammatory bowel disease.

  9. Sub-Study 1: Change in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) [ Time Frame: Baseline (Week 0) to Week 52 ]
    The FACIT-F questionnaire was developed to assess fatigue.

  10. Sub-Study 1: Percentage of Participants with Hospitalizations due to Crohn's Disease (CD) [ Time Frame: Up to Week 52 ]
    This is assessed by reviewing participant's hospitalization data.

  11. Sub-Study 1: Percentage of Participants with Resolution of Extra-Intestinal Manifestation (EIMs) , in Participants with EIMs at Baseline [ Time Frame: Week 52 ]
    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.


Eligibility Criteria
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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.


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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 achieve clinical response in Study M14-431 or Study M14-433.
  • Participant completes study procedures in the parent study. The final endoscopy for Studies M14-431 or M14-433 may be missing, if the endoscopy cannot be performed during the COVID-19 pandemic.

For Substudy 2:

  • Participant completes Substudy 1. The Week 52 endoscopy may be missing, if the endoscopy cannot be performed during the COVID-19 pandemic.
  • Participant who achieved clincal response at the time descibed in the protocol and completes study procedures in the parent study/ substudy.

For Substudy 3:

  • Participant is an ongoing participant in Substudy 2 for at least 12 months.

  • Participant is in stable remission for at least 6 months defined as:

    1. CDAI < 150
    2. CRP < 5 mg/L and FCP < 250 mg/kg AND
    3. Participant has not been on locally acting (rectal or suppository) or systemic corticosteroids for CD => 90 days prior to the entry of Substudy 3.

Exclusion Criteria:

For Substudies 1,2 and 3:

  • 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 or 2 of Study M14-430 that in the investigator's judgment makes the participant unsuitable for this study.
  • Participant at the final visit of M14-431 or M14-433 with any active or chronic recurring infections based on the investigator's assessment that makes the participant an unsuitable candidate for the study. Participants with serious infections undergoing treatment may be enrolled BUT NOT dosed until the infection treatment has been completed and the infection is resolved, 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 or 2 of Study M14-430 (Week 52).

For Substudy 3 only:

  • Total SES-CD >4 and/or subscore >1 in any segment in the Substudy 2 annual ileo-colonoscopy, if performed within 6 months prior to Week 0 of Substudy 3.
  • Received any new medication or increase of the dose of current concomitant medication for the treatment of CD in the past 3 months.
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): NCT03345823


Locations
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Sponsors and Collaborators
AbbVie
Investigators
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Study Director: ABBVIE INC. AbbVie
More Information
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Additional Information:

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Responsible Party: AbbVie
ClinicalTrials.gov Identifier: NCT03345823    
Other Study ID Numbers: M14-430
2017-001225-41 ( EudraCT Number )
First Posted: November 17, 2017    Key Record Dates
Last Update Posted: May 18, 2023
Last Verified: May 2023
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, analyses plans, 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 visit https://vivli.org/ ourmember/abbvie/
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 and execution of a data sharing statement. Data requests can be submitted at any time after approval in the US and/or EU and a primary manuscript is accepted for publication. For more information on the process, or to submit a request, visit the following link https://www.abbvieclinicaltrials.com/hcp/data-sharing/
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
ABT-494
Extension Study
Efficacy
 Safety
Crohn's Disease
Maintenance Study
Additional relevant MeSH terms:
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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