Crohn's Disease: Efficacy, Safety, and Pharmacokinetics of Upadacitinib in Pediatric Subjects With Moderately to Severely Active Crohn's Disease

Crohn's Disease Clinical Trial

Official title:

A Phase 3 Multicenter Study to Evaluate Efficacy, Safety, and Pharmacokinetics of Upadacitinib With Open-Label Induction, Randomized, Double-Blind Maintenance and Open-Label Long-Term Extension in Pediatric Subjects With Moderately to Severely Active Crohn's Disease and Inadequate Response, Intolerance, or Medical Contraindications to Corticosteroids, Immunosuppressants, and/or Biologic Therapy

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06332534
• Other study ID #: M14-671
• Status: Not yet recruiting
• Phase: Phase 3
• Start date: July 26, 2024
• Est. completion date: December 20, 2034

Study information

• Verified date: March 2024
• Source: AbbVie
• Contact: ABBVIE CALL CENTER
• Phone: 844-663-3742
• Email: abbvieclinicaltrials[@]abbvie.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 110
• Est. completion date: December 20, 2034
• Est. primary completion date: March 22, 2032
• Accepts healthy volunteers: No
• Gender: All
• Age group: 2 Years to 17 Years

Eligibility

Inclusion Criteria:

• 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).

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 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);

• 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.

Related Conditions & MeSH terms

• Crohn Disease
• Crohn's Disease

Intervention

Drug:
• Upadacitinib
Oral Solution/ Extended-Release Tablets

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
AbbVie

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	At Week 64
Primary	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.	At Week 64
Primary	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.	Through Week 156
Secondary	Achievement of clinical remission per PCDAI	Clinical remission per PCDAI is defined as PCDAI = 10.	Week 12
Secondary	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.	Week 12
Secondary	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	Week 12
Secondary	Achievement of clinical response per PCDAI	Clinical response is defined as reduction in PCDAI of = 15 points from Baseline	Week 12
Secondary	Achievement of clinical response per PCDAI at Week 64 in participants who achieved clinical response per PCDAI at Week 12		Week 64
Secondary	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	Week 64
Secondary	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]).	Week 64

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