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

AbbVie

Status and phase: Completed; Phase 3

Conditions: Crohn's Disease

Treatments: Drug: Upadacitinib; Drug: Matching Placebo for Upadacitinib

Study type: Interventional

Funder types: Industry

Identifiers

NCT03345836

2017-001226-18 (EudraCT Number)

M14-431

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 participants with moderately and severely active Crohn's disease (CD).

Enrollment: 624 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 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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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624 participants in 6 patient groups, including a placebo group

Part 1 (Double-blind): Placebo

Placebo Comparator group

Description:

Participants received upadacitinib matching placebo tablets, orally, once daily (QD) for 12 weeks during the Double-blind (DB) Induction Period.

Treatment:

Drug: Matching Placebo for Upadacitinib

Part 1 (Double-blind): Upadacitinib 45 mg

Experimental group

Description:

Participants received upadacitinib 45 mg tablets, orally, QD for 12 weeks during the DB Induction Period.

Treatment:

Drug: Upadacitinib

Part 2 (Open-label): Upadacitinib 45 mg

Experimental group

Description:

Participants received upadacitinib 45 mg tablets, orally, QD for 12 weeks during the Open-label (OL) Induction Period.

Treatment:

Drug: Upadacitinib

Part 3 (Extended Treatment DB): Upadacitinib 45 mg From Part 1 DB Placebo

Experimental group

Description:

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.

Treatment:

Drug: Upadacitinib

Part 3 (Extended Treatment DB): Upadacitinib 30 mg From Part 1 DB Upadacitinib 45 mg

Experimental group

Description:

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.

Treatment:

Drug: Upadacitinib

Part 3 (Extended Treatment OL): Upadacitinib 30 mg From Part 2 OL Upadacitinib 45 mg

Experimental group

Description:

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.

Treatment:

Drug: Upadacitinib