Crohn's Disease: Efficacy, Safety, and Pharmacokinetics of Upadacitinib in Pediatric Subjects With Moderately to Severely Active Crohn's Disease
Purpose
Crohn's disease (CD) is a long-lasting disease that causes severe inflammation (redness, swelling), in the digestive tract, most often affecting the bowels. It can cause many different symptoms including abdominal pain, diarrhea, tiredness, and weight loss. This study will assess how safe and effective oral Upadacitinib is in treating moderately to severely active Crohn's Disease in pediatric participants aged 2 to 18 years old who have had inadequate response, loss of response, intolerance, or medical contraindications to corticosteroids, immunosuppressants, and/or biologic therapy. Upadacitinib (RINVOQ) is a drug approved in adults for moderate- to severely active CD and is being developed for moderate- to severely active CD in pediatric participants. This study is conducted in 2 periods: Period 1 is comprised of two phases: a 12-week open-label induction phase which means that the study doctor and participants know that participants will receive UPA Dose-A (or the adult equivalent based on body weight) followed by a 52-week double-blind maintenance phase meaning that neither the participants nor the study doctors will know which dose of upadacitinib will be given (UPA Dose B or Dose C). Period 2 is a 156-week open-label extension of Period 1. Approximately 110 pediatric participants with moderate to severely active CD will be enrolled at approximately 92 sites worldwide. Participants will receive upadacitinib oral tablets once daily or oral solution twice daily at approximately the same time each day, with or without food. Participants will have a safety follow up for 30 days after discontinuation from any time point within the study. There may be higher treatment burden for participants in this trial compared to their standard of care (due to study procedures). Participants will attend regular (weekly, monthly) visits during the study at a hospital or clinic. The effect of the treatment will be checked by medical assessments, blood tests, checking for side effects and completing questionnaires.
Condition
- Crohn's Disease
Eligibility
- Eligible Ages
- Between 2 Years and 17 Years
- Eligible Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- Weight at Screening and Baseline must be >= 10 kg - Moderate to severe Crohn's Disease (CD) defined as Pediatric Crohn's Disease Activity Index (PCDAI) > 30 and endoscopic evidence of mucosal inflammation as documented by a centrally read SES-CD of >= 6 (or SES-CD of >=4 for isolated ileal disease) excluding the presence of narrowing component. - Documented diagnosis of CD prior to Baseline, confirmed by colonoscopy during the screening period, with exclusion of current infection, colonic dysplasia and/or malignancy. Appropriate documentation of biopsy results consistent with the diagnosis of CD, in the assessment of the investigator, must be available - Demonstrated an inadequate response, loss of response, or intolerance to corticosteroids, immunomodulators (IMMs), and/or biologic therapy or in whom use of those therapies is medically contraindicated. For participants in the US and South Korea, participants must have demonstrated an inadequate response, loss of response, or intolerance to one or more anti-TNFs (tumor necrosis factor).
Exclusion Criteria
- History of: - A diagnosis of CD prior to 2 years of age. - Currently known complications of CD such as: - Active abscess (abdominal or perianal); - Symptomatic bowel strictures; - More than 2 missing segments of the following 5 intestinal segments: terminal ileum, right colon, transverse colon, sigmoid and left colon, and rectum; - Ostomy or ileoanal pouch; - Surgical bowel resection within the past 3 months prior to Baseline, or a history of more than 3 bowel resections. - Japan participants only: positive result of beta-D-glucan or two consecutive indeterminate results of beta-D-glucan during the Screening period (screening for Pneumocystis jiroveci infection) - History of any of the following: - Current diagnosis of ulcerative colitis (UC), indeterminate colitis, or monogenic inflammatory bowel disease (IBD); - Fulminant colitis or toxic megacolon; - Gastrointestinal (GI) perforation (other than due to appendicitis or mechanical injury), diverticulitis, or significantly increased risk for GI perforation per investigator judgment including history of volvulus and/or intussusception (telescoping of bowels); - Current diagnosis of any primary immune deficiency - Conditions that could interfere with drug absorption including but not limited to short bowel syndrome or gastric bypass surgery; subjects with a history of gastric banding/segmentation are not excluded.
Study Design
- Phase
- Phase 3
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Sequential Assignment
- Primary Purpose
- Treatment
- Masking
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Arm Groups
| Arm | Description | Assigned Intervention |
|---|---|---|
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Experimental Period 1: Open Label Induction Phase (Dose A) |
All participants in the open label induction phase of Period 1 will receive upadacitinib Dose A for 12 weeks based on body weight. |
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Experimental Period 1: Double-Blind Maintenance Phase (Dose B) |
Clinical responders per PCDAI at the end of open label induction phase of Period 1 will be randomly assigned to receive Dose B or C for 52 weeks (oral solution dose will be based on body weight) |
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|
Experimental Period 1: Double-Blind Maintenance Phase (Dose C) |
Clinical responders per PCDAI at the end of open label induction phase of Period 1 will be randomly assigned to receive either upadacitinib Dose C or B for 52 weeks (oral solution dose will be based on body weight) |
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Experimental Period 2: Open Label Long-Term Extension Phase Cohort 1 |
Participants receiving double-blind maintenance therapy with upadacitinib Dose B or upadacitinib Dose C daily in Period 1 who complete the Week 64 visit will receive upadacitinib Dose B daily for up to 156 weeks. |
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Experimental Period 2: Open Label Long-Term Extension Phase Cohort 2 |
Participants who were receiving rescue therapy with open-label upadacitinib Dose C during maintenance phase in Period 1 and completed the Week 64 visit will continue to receive upadacitinib Dose C daily for up to 156 weeks. |
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Experimental Period 2: Open Label Long-Term Extension Phase Cohort 3 |
Participants who did not achieve clinical response per PCDAI at Week 12 of Period 1 will receive an extended treatment with open-label upadacitinib Dose C daily for an additional 12 weeks. If they are responders after 12 weeks extended treatment, they will continue, otherwise they may be discontinued at the discretion of the investigator |
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Recruiting Locations
Oakland, California 94609
Palo Alto, California 94304
Aurora, Colorado 80045
Hartford, Connecticut 06106
Peoria, Illinois 61637-0001
Indianapolis, Indiana 46202
Boston, Massachusetts 02115
Minneapolis, Minnesota 55413-2195
New York, New York 10029
Chapel Hill, North Carolina 27514-4220
Cleveland, Ohio 44106
Philadelphia, Pennsylvania 19104-4319
Bayamón, Puerto Rico 00960
Dorado, Puerto Rico 00646
San Juan, Puerto Rico 00909-1711
More Details
- Status
- Recruiting
- Sponsor
- AbbVie