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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
110
Oral Solution/ Extended-Release Tablets
UCSF Benioff Children's Hospital - Oakland /ID# 262217
Oakland, California, United States
RECRUITINGLucile Packard Children's Hospital /ID# 262193
Palo Alto, California, United States
RECRUITINGChildren's Hospital Colorado - Aurora /ID# 262207
Aurora, Colorado, United States
RECRUITINGConnecticut Children's Medical Center - Hartford /ID# 262256
Hartford, Connecticut, United States
Percentage of participants who achieved clinical response per the Pediatric Crohn's Disease Activity Index (PCDAI) at Week 12, with clinical remission per the PCDAI at Week 64
PCDAI is an index used to measure disease activity of pediatric patients with Crohn's disease assessing abdominal pain, stool frequency, patient functioning, hematocrit, erythrocyte sedimentation rate, albumin, weight, height, abdomen, perirectal disease, and extraintestinal manifestations. It ranges from 0 to 100; higher scores indicate more active disease. Clinical remission was defined as PCDAI ≤ 10.
Time frame: At Week 64
Achievement of endoscopic response at Week 64 in participants who achieved clinical response per PCDAI at Week 12.
Endoscopic response is defined as \> 50% reduction in Simple Endoscopic Score for Crohn's Disease (SES-CD) score from Baseline (or for participants with a Baseline SES-CD of 4, at least a 2-point reduction from Baseline), as scored by a central reader.
Time frame: At Week 64
Number of Participants with Adverse Events
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.
Time frame: Through Week 156
Achievement of clinical remission per PCDAI
Clinical remission per PCDAI is defined as PCDAI ≤ 10.
Time frame: Week 12
Achievement of endoscopic response
Endoscopic response is defined as \> 50% reduction in SES-CD score from Baseline (or for participants with a Baseline SES-CD of 4, at least a 2-point reduction from Baseline), as scored by a central reader.
Time frame: Week 12
Achievement of endoscopic remission
Endoscopic remission is defined as SES-CD ≤ 4 with at least a 2-point reduction from Baseline and no subscore \> 1, as scored by a central reader
Time frame: Week 12
Achievement of clinical response per PCDAI
Clinical response is defined as reduction in PCDAI of ≥ 15 points from Baseline
Time frame: Week 12
Achievement of clinical response per PCDAI at Week 64 in participants who achieved clinical response per PCDAI at Week 12
Time frame: Week 64
Achievement of endoscopic remission at Week 64 in participants who achieved clinical response per PCDAI at Week 12
Endoscopic remission is defined as SES-CD ≤ 4 with at least a 2-point reduction from Baseline and no subscore \> 1, as scored by a central reader
Time frame: Week 64
Achievement of corticosteroid (CS)-free clinical remission per PCDAI at Week 64 in participants who achieved clinical response per PCDAI at Week 12
CS-free clinical remission per PCDAI: clinical remission per PCDAI and not receiving corticosteroids at Week 12 (for Period 1 induction endpoint\[s\]); or for at least 90 days prior to the study visit at which endpoint is assessed (for Period 1 maintenance endpoint\[s\] and Period 2 endpoint\[s\]).
Time frame: Week 64
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OSF St. Francis Medical Center /ID# 262192
Peoria, Illinois, United States
RECRUITINGIndiana University Health Riley Hospital for Children /ID# 262215
Indianapolis, Indiana, United States
RECRUITINGBoston Children's Hospital /ID# 262191
Boston, Massachusetts, United States
RECRUITINGMNGI Digestive Health, P. A. /ID# 262204
Minneapolis, Minnesota, United States
RECRUITINGIcahn School of Medicine at Mount Sinai /ID# 262216
New York, New York, United States
RECRUITINGUniv NC Chapel Hill /ID# 262198
Chapel Hill, North Carolina, United States
RECRUITING...and 75 more locations