A Study of the Efficacy and Safety of Upadacitinib (ABT-494) in Subjects With Moderately to Severely Active Crohn's Disease Who Have Inadequately Responded to or Are Intolerant to Biologic Therapy

Overview

About this study

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

Participation eligibility

Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. There is no guarantee that every individual who qualifies and wants to participate in a trial will be enrolled. Contact the study team to discuss study eligibility and potential participation.

Inclusion Criteria:

  • Confirmed diagnosis of CD for at least 3 months prior to Baseline. Appropriate documentation of biopsy results consistent with the diagnosis of CD, as determined by the investigator, must be available.
  • SES-CD (excluding the presence of narrowing component) ≥ 6 (or ≥ 4 for subjects with isolated ileal disease), as confirmed by a central reader.
  • Average daily liquid/very soft SF ≥ 4.0 AND/OR average daily AP score ≥ 2.0 at Baseline.
  • Demonstrated an inadequate response or intolerance to one or more of the following biologic agents:
    • At least one 6-week induction regimen of infliximab (≥ 5 mg/kg intravenous [IV] at Baseline and Weeks 2, and 6);
    • At least one 4-week induction regimen of adalimumab (one 160 mg subcutaneous [SC] dose at Baseline, followed by one 80 mg SC dose at Week 2 [or one 80 mg SC dose at Baseline, followed by one 40 mg SC dose at Week 2, in countries where this dosing regimen is approved]);
    • At least one 4-week induction regimen of certolizumab pegol (400 mg SC at Baseline and Weeks 2, and 4);
    • At least one 6-week induction regimen of vedolizumab (300 mg IV at Baseline and Weeks 2, and 6);
    • At least one 8-week induction regimen of ustekinumab [260 mg (≤ 55 kg) or 390 mg (> 55 to ≤ 85 kg) or 520 mg (> 85 kg) IV, followed by 90 mg SC at Week 8];
    • Recurrence of symptoms during scheduled maintenance dosing following prior clinical benefit of the above biologics;
    • Intolerance to a biologic may include, but not limited to infusion-related reaction, rash, serum sickness, anaphylaxis, elevated liver enzymes, demyelination, congestive heart failure, infection. Demonstration of intolerance requires no minimum dose or duration of use.

Exclusion Criteria

  • Subject with a current diagnosis of ulcerative colitis or indeterminate colitis.
  • Concomitant Medications and Treatments
  • Subject on CD related antibiotics who:
    • has not been on stable doses of these medications for at least 14 days prior to Baseline; or
    • has discontinued these medications within 14 days of Baseline.
  • Subject on oral aminosalicylates who:
    • has not been on stable doses of these medications for at least 14 days prior to Baseline; or
    • has discontinued these medications within 14 days of Baseline.
  • Subject on corticosteroids who meet the following:
    • prednisone or equivalent dose > 30 mg/day; or
    • budesonide > 9 mg/day; or
    • has not been on the current course for at least 14 days prior to Baseline and on a stable dose for at least 7 days prior to Baseline.
  • Subject on MTX who:
    • has not been on the current course for ≥ 42 days prior to Baseline; and
    • has not been on a stable dose for ≥ 28 days prior to Baseline

CD Related

  • Subject with the following known complications of CD:
    • abscess (abdominal or peri-anal);
    • symptomatic bowel strictures;
    • > 2 missing segments of the following 5 segments: terminal ileum, right colon, transverse colon, sigmoid and left colon, and rectum;
    • fulminant colitis;
    • toxic megacolon;
    • or any other manifestation that might require surgery while enrolled in the study.
  • Subject with ostomy or ileoanal pouch.
  • Subject diagnosed with conditions that could interfere with drug absorption including but not limited to short gut or short bowel syndrome.
  • Subject with surgical bowel resection within the past 3 months prior to Baseline, or a history of > 3 bowel resections.

Safety

  • Laboratory values meeting the following criteria within the Screening period prior to the first dose of study drug:
    • Serum aspartate transaminase (AST) or alanine transaminase (ALT) > 2.0 × upper limit of the reference range (ULN);
    • Total white blood cell count < 2500/μL;
    • Estimated glomerular filtration rate by simplified 4-variable Modification of Diet in Renal Disease (MDRD) formula < 30 mL/min/1.73 m2;
    • Hemoglobin < 9 g/dL;
    • Platelet count < 100,000/μL;
    • Absolute neutrophil count < 1200/μL;
    • Absolute lymphocyte count < 750/μL.

 

Participating Mayo Clinic locations

Study statuses change often. Please contact the study team for the most up-to-date information regarding possible participation.

Mayo Clinic Location Status Contact

Rochester, Minn.

Mayo Clinic principal investigator

Edward Loftus, M.D.

Open for enrollment

Contact information:

IBD Clinical Research Unit

(507) 284-5908

More information

Publications

Publications are currently not available

Study Results Summary

Not yet available

Supplemental Study Information

Not yet available

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CLS-20401448

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