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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

Phase 3
Active, not recruiting
Conditions
Crohn's Disease
Interventions
Registration Number
NCT03345823
Lead Sponsor
AbbVie
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.

Detailed Description

Not available

Recruitment & Eligibility

Status
ACTIVE_NOT_RECRUITING
Sex
All
Target Recruitment
747
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 clinical response at the time described in the protocol and completes study procedures in the parent study/ substudy.
Exclusion Criteria

For Substudies 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 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 of Study M14-430 (Week 52).

Study & Design

Study Type
INTERVENTIONAL
Study Design
SEQUENTIAL
Arm && Interventions
GroupInterventionDescription
Substudy 1: Cohort 2 PlaceboPlacebo for UpadacitinibThis 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.
Substudy 2: Cohort 5 PlaceboPlacebo for UpadacitinibThis is a long-term extension group which includes participants who complete Substudy 1 and will receive placebo for 240 weeks.
Substudy 1: Cohort 1 PlaceboPlacebo for UpadacitinibThis 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.
Substudy 1: Cohort 1 Upadacitinib Dose BUpadacitinibThis 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.
Substudy 1: Cohort 1 Upadacitinib Dose AUpadacitinibThis 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.
Substudy 2: Cohort 5 Upadacitinib Dose BUpadacitinibThis is a long-term extension group which includes participants who complete Substudy 1 and will receive upadacitinib dose B for 240 weeks.
Substudy 1: Cohort 3 Upadacitinib Dose BUpadacitinibThis 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.
Substudy 2: Cohort 4 Upadacitinib Dose BUpadacitinibThis 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.
Substudy 2: Cohort 5 Upadacitinib Dose AUpadacitinibThis is a long-term extension group which includes participants who complete Substudy 1 and will receive upadacitinib dose A for 240 weeks.
Primary Outcome Measures
NameTimeMethod
Sub-Study 1: Percentage of Participants with Clinical Remission per Crohn's Disease Activity Index (CDAI)Week 52

Clinical remission per CDAI is defined as CDAI \<150.

Sub-Study 1: Percentage of Participants with Endoscopic ResponseWeek 52

Endoscopic response is defined as decrease in Simple Endoscopic Score for Crohn's Disease (SES-CD) from Baseline.

Number of Participants with Adverse EventsThrough 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
NameTimeMethod
Sub-Study 1: Percentage of Participants with Endoscopic RemissionWeek 52

Endoscopic remission is defined per Simplified Endoscopic Score for Crohn's Disease (SES-CD).

Sub-Study 1: Percentage of Participants without Corticosteroid use for Crohn's Disease Among All ParticipantsWeek 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.

Sub-Study 1: Percentage of Participants with Clinical Remission per CDAI and Endoscopic RemissionWeek 52

Clinical remission per CDAI is defined as CDAI \<150. Endoscopic remission is defined per SES-CD.

Sub-Study 1: Percentage of Participants with Clinical Remission per CDAIThrough 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).

Sub-Study 1: Percentage of Participants with Clinical Remission per Patient-Reported Outcomes (PROs)Week 52

Clinical remission is defined based on average daily stool frequency (SF) AND average daily abdominal pain (AP) score.

Sub-Study 1: Percentage of Participants Achieving Clinical Response 100 (CR-100)Week 52

Decrease of at least 100 points in CDAI from Baseline.

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.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.

Sub-Study 1: Change in Inflammatory Bowel Disease Questionnaire (IBDQ)Baseline (Week 0) to Week 52

The IBDQ is used to assess the quality of life of patients with inflammatory bowel disease.

Sub-Study 1: Change in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F)Baseline (Week 0) to Week 52

The FACIT-F questionnaire was developed to assess fatigue.

Sub-Study 1: Percentage of Participants with Hospitalizations due to Crohn's Disease (CD)Up to Week 52

This is assessed by reviewing participant's hospitalization data.

Sub-Study 1: Percentage of Participants with Resolution of Extra-Intestinal Manifestation (EIMs) , in Participants with EIMs at BaselineWeek 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.

Trial Locations

Locations (466)

East View Medical Research, LLC /ID# 171132

🇺🇸

Mobile, Alabama, United States

CB Flock Research Corporation /ID# 166239

🇺🇸

Mobile, Alabama, United States

Delsol Research Management, Ll /Id# 170164

🇺🇸

Chandler, Arizona, United States

Duplicate_HonorHealth Research Institute - Shea /ID# 164725

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Scottsdale, Arizona, United States

Arizona Arthritis & Rheumatology Research, PLLC /ID# 164702

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Sun City, Arizona, United States

Southern California Res. Ctr. /ID# 169653

🇺🇸

Coronado, California, United States

Citrus Valley Gastroenterology /ID# 166230

🇺🇸

Covina, California, United States

Hoag Memorial Hosp Presbyterian /ID# 222538

🇺🇸

Irvine, California, United States

UC San Diego Health System /ID# 164763

🇺🇸

La Jolla, California, United States

United Medical Doctors /ID# 207458

🇺🇸

Los Alamitos, California, United States

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East View Medical Research, LLC /ID# 171132
🇺🇸Mobile, Alabama, United States

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