A Study of the Efficacy and Safety of Upadacitinib in Participants With Moderately to Severely Active Crohn's Disease Who Have Inadequately Responded to or Are Intolerant to Conventional and/or Biologic Therapies (U-EXCEL)

AbbVie

Status and phase: Completed; Phase 3

Conditions: Crohn's Disease

Treatments: Drug: Upadacitinib; Drug: Placebo for Upadacitinib

Study type: Interventional

Funder types: Industry

Identifiers

NCT03345849

2017-001240-35 (EudraCT Number)

M14-433

Details and patient eligibility

About

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

Full description

This study includes two parts:

• Part 1: a randomized double-blind placebo-controlled induction period and
• Part 2: an extended treatment period for non-responders from Part 1.

In Part 1, participants will be randomized in a 2:1 ratio to upadacitinib 45 mg once daily (QD) or matching placebo for 12 weeks. The randomization will be stratified by baseline corticosteroid use (yes or no), endoscopic disease severity (Simplified Endoscopic Score for Crohn's disease [SES-CD] < 15 and ≥ 15), and number of prior biologics with prior inadequate response or intolerance (0, 1, > 1).

Participants who do not achieve clinical response at Week 12 will be able to enroll in Part 2 to receive a double-blind extended treatment with upadacitinib until Week 24. Clinical response is defined as a ≥ 30% decrease in average daily very soft or liquid stool frequency (SF) and/or ≥ 30% decrease in average daily abdominal pain (AP) score (both not worse than Baseline).

Participants who achieve clinical response at Week 12 may be eligible to enter the 52-week, double-blind, maintenance portion of Study M14-430 (NCT03345823).

Enrollment: 526 patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

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 one or more conventional and/or biologic therapies (oral locally acting steroids, intravenous or oral corticosteroids, immunosuppressants or biologic therapies for CD), in the opinion of the investigator.

  • Note: Participants who have had inadequate response or intolerance to conventional therapy who have received prior biologic may be enrolled; however, participants must have discontinued the biologic for reasons other than inadequate response or intolerance (e.g., change of insurance, well controlled disease).

• 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, > 2 entire missing segments of the following 5 segments: terminal ileum, right colon, transverse colon, sigmoid and left colon, and rectum, 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 analyses show abnormal results.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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526 participants in 2 patient groups, including a placebo group

Placebo

Placebo Comparator group

Description:

Participants will receive placebo once daily for 12 weeks in Part 1. Clinical non-responders will receive 45 mg upadacitinib once daily for 12 weeks in Part 2.

Treatment:

Drug: Placebo for Upadacitinib

Drug: Upadacitinib

Upadacitinib

Experimental group

Description:

Participants will receive 45 mg upadacitinib once daily for 12 weeks in Part 1. Clinical non-responders will receive 30 mg upadacitinib once daily for 12 weeks in Part 2.

Treatment:

Drug: Upadacitinib