Crohn's Disease: Efficacy, Safety, and Pharmacokinetics of Upadacitinib in Pediatric Subjects With Moderately to Severely Active Crohn's Disease
- Registration Number
- NCT06332534
- Lead Sponsor
- AbbVie
- Brief Summary
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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 110
- Weight at Screening and Baseline must be ≥ 10 kg
- Moderate to severe CD defined as 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, IMMs, and/or biologic therapy or in whom use of those therapies is medically contraindicated. For participants in the US, participants must have demonstrated an inadequate response, loss or response, or intolerance to one or more anti-TNFs (tumor necrosis factor).
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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.
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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)
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History of any of the following:
- Current diagnosis of UC, indeterminate colitis, or monogenic IBD;
- Fulminant colitis or toxic megacolon;
- Gastrointestinal 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);
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Current diagnosis of any primary immune deficiency
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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
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Period 1: Open Label Induction Phase (Dose A) Upadacitinib All participants in the open label induction phase of Period 1 will receive upadacitinib Dose A for 12 weeks based on body weight. Period 2: Open Label Long-Term Extension Phase Cohort 3 Upadacitinib 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 Period 2: Open Label Long-Term Extension Phase Cohort 1 Upadacitinib 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. Period 1: Double-Blind Maintenance Phase (Dose C) Upadacitinib 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) Period 1: Double-Blind Maintenance Phase (Dose B) Upadacitinib 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) Period 2: Open Label Long-Term Extension Phase Cohort 2 Upadacitinib 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.
- Primary Outcome Measures
Name Time Method Achievement of endoscopic response at Week 64 in participants who achieved clinical response per PCDAI at Week 12. At Week 64 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.
Number of Participants with Adverse Events Through Week 156 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.
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 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.
- Secondary Outcome Measures
Name Time Method Achievement of clinical remission per PCDAI Week 12 Clinical remission per PCDAI is defined as PCDAI ≤ 10.
Achievement of endoscopic remission 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
Achievement of clinical response per PCDAI Week 12 Clinical response is defined as reduction in PCDAI of ≥ 15 points from Baseline
Achievement of corticosteroid (CS)-free clinical remission per PCDAI at Week 64 in participants who achieved clinical response per PCDAI at Week 12 Week 64 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\[s\]).
Achievement of endoscopic response Week 12 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.
Achievement of clinical response per PCDAI at Week 64 in participants who achieved clinical response per PCDAI at Week 12 Week 64 Achievement of endoscopic remission at Week 64 in participants who achieved clinical response per PCDAI at Week 12 Week 64 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
Trial Locations
- Locations (80)
UCSF Benioff Children's Hospital - Oakland /ID# 262217
🇺🇸Oakland, California, United States
Childrens Hospital Colorado - Aurora /ID# 262207
🇺🇸Aurora, Colorado, United States
Connecticut Children's Medical Center - Hartford /ID# 262256
🇺🇸Hartford, Connecticut, United States
OSF St. Francis Medical Center /ID# 262192
🇺🇸Peoria, Illinois, United States
Indiana University Health Riley Hospital for Children /ID# 262215
🇺🇸Indianapolis, Indiana, United States
MNGI Digestive Health, P. A. /ID# 262204
🇺🇸Minneapolis, Minnesota, United States
Icahn School of Medicine at Mount Sinai /ID# 262216
🇺🇸New York, New York, United States
Univ NC Chapel Hill /ID# 262198
🇺🇸Chapel Hill, North Carolina, United States
UH Cleveland Medical Center /ID# 262188
🇺🇸Cleveland, Ohio, United States
Children's Hospital of Philadelphia - Main /ID# 262197
🇺🇸Philadelphia, Pennsylvania, United States
Scroll for more (70 remaining)UCSF Benioff Children's Hospital - Oakland /ID# 262217🇺🇸Oakland, California, United States