Study to Assess Adverse Events, Change in Disease Activity, and How Oral Upadacitinib Moves Through the Body of Pediatric Participants With Moderately to Severely Active Ulcerative Colitis. (U-ASTOUND)

AbbVie

Status and phase: Enrolling; Phase 3

Conditions: Ulcerative Colitis

Treatments: Drug: Upadacitinib

Study type: Interventional

Funder types: Industry

Identifiers

NCT05782907

2022-501788-41-00 (Other Identifier)

M14-658

Details and patient eligibility

About

Ulcerative colitis (UC) is a type of inflammatory bowel disease that causes inflammation and bleeding from the lining of the rectum and colon (large intestine). This study will assess how safe and effective Upadacitinib is in treating pediatric participants with UC. Adverse events and change in disease activity will be assessed.

Upadacitinib (RINVOQ) is a drug approved in adults for moderate- to severely active UC and is being developed for moderate- to severely active UC in pediatric participants. This study is conducted in 2 periods: Period 1 is comprised of two phases: an 8-week open-label induction phase which means that the study doctor and patients know that participants will receive UPA Dose-A (or the adult equivalent based on body weight) followed by a 44-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 260 week open-label extension (OLE) of Period 1. Approximately 110 pediatric participants with moderate to severely active UC will be enrolled at up to 100 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 be followed up for 30 days after each phase (i.e. after induction, maintenance, OLE) and only if a participant doesn't continue into the next phase.

There may be higher treatment burden for participants in this trial compared to their standard of care. Participants will attend regular 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.

Enrollment: 110 estimated patients

Sex: All

Ages: 2 to 17 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Active UC with an AMS of 5 to 9 points and endoscopic subscore of 2 to 3.
• Demonstrate an inadequate response, loss of response, intolerance, or medical contraindications to corticosteroids, immunosuppressants, and/or biologic therapy.

Exclusion criteria

• Partcipants with previous exposure to JAK inhibitors (e.g., tofacitinib, baricitinib, filgotinib, upadacitinib).
• Females who are pregnant, breastfeeding, or considering becoming pregnant during the study and for approximately 30 days after the last dose of study drug.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Sequential Assignment

Masking: Quadruple Blind

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110 participants in 5 patient groups

Period 1- Open Label Induction Phase

Experimental group

Description:

All participants in open label induction phase of Period 1 will receive upadacitinib Dose A for 8 weeks based on body weight.

Treatment:

Drug: Upadacitinib

Period 1- Double Blind Maintenance Phase

Experimental group

Description:

Clinical responders at the end of open label induction phase of Period 1 will be randomly assigned to receive either upadacitinib Dose B or Dose C for 44 weeks based on body weight.

Treatment:

Drug: Upadacitinib

Period 2- Open Label Long Term Extension Phase Arm A

Experimental group

Description:

Clinical non-responders outside of US after Period 1 induction phase will receive upadacitinib Dose A daily for 8 week extended induction phase in open label long term extension (OLE) Period 2. Clinical responders from extended induction phase in OLE will receive upadacitinib Dose B daily for up to 252 weeks in OLE period 2.

Treatment:

Drug: Upadacitinib

Period 2- Open Label Long Term Extension Phase Arm B

Experimental group

Description:

Clinical non-responders in US after Period 1 induction phase or clinical responders with loss of response during maintenance phase will receive upadacitinib Dose B daily for up to 260 weeks in OLE Period 2.

Treatment:

Drug: Upadacitinib

Period 2- Long Term Extension Phase Arm C

Experimental group

Description:

Clinical responders who complete Period 1 through Week 52 will receive upadacitinib Dose C daily for up to 260 weeks in OLE Period 2.

Treatment:

Drug: Upadacitinib