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)

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 Ulcerative Colitis and Inadequate Response, Intolerance, or Medical Contraindications to Corticosteroids, Immunosuppressants, and/or Biologic Therapy

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Ulcerative Colitis
• Intervention / Treatment: Drug: Upadacitinib

• Study Type: Interventional
• Enrollment (Actual): 122
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Westmead, New South Wales, Australia, 2145
      • Children's Hospital at Westmead /ID# 255556
  • Queensland
    • South Brisbane, Queensland, Australia, 4101
      • Queensland Children's Hospital /ID# 261032
  • Victoria
    • Clayton, Victoria, Australia, 3168
      • Monash Health - Monash Medical Centre - Clayton /ID# 254726
  • Western Australia
    • Perth, Western Australia, Australia, 6009
      • Perth Children'S Hospital /ID# 254727
• Belgium
  • Antwerpen
    • Edegem, Antwerpen, Belgium, 2650
      • Universitair Ziekenhuis Antwerpen /ID# 251184
  • Vlaams-Brabant
    • Leuven, Vlaams-Brabant, Belgium, 3000
      • Universitair Ziekenhuis Leuven /ID# 251185
• Brazil
  • Paraná
    • Curitiba, Paraná, Brazil, 80250-060
      • Hospital Pequeno Príncipe /ID# 251911
  • São Paulo
    • Campinas, São Paulo, Brazil, 13034-685
      • Hospital e Maternidade Celso Pierro - PUC-Campinas /ID# 251912
    • São Paulo, São Paulo, Brazil, 04543-011
      • Rocco & Nazato Servicos Medicos /ID# 251910
• Bulgaria
  • Plovdiv, Bulgaria, 4002
    • UMHAT Sveti Georgi /ID# 251949
  • Sofia, Bulgaria, 1606
    • Specialized Hospital For Active Treatment Of Children Diseases Prof. Ivan Mitev /ID# 251285
  • Varna, Bulgaria, 9009
    • UMHAT Multiprofile Hospital for Active Treatment Sveta Marina /ID# 251948
• Canada
  • Alberta
    • Edmonton, Alberta, Canada, T6G 1C9
      • Alberta Health Services /ID# 252088
    • Edmonton, Alberta, Canada, T6L 6K3
      • South Edmonton Gastroenterology /ID# 276669
  • British Columbia
    • Vancouver, British Columbia, Canada, V6H 3V4
      • BC Children's Hospital /ID# 250947
  • Nova Scotia
    • Halifax, Nova Scotia, Canada, B3K 6R8
      • IWK Health Center /ID# 250943
  • Ontario
    • Toronto, Ontario, Canada, M5G 1X8
      • Hospital for Sick Children /ID# 250945
• Czechia
  • Plzen-jih
    • Pilsen, Plzen-jih, Czechia, 323 00
      • Fakultní Nemocnice Plzeň-Lochotín /ID# 253284
  • Praha 5
    • Prague, Praha 5, Czechia, 150 06
      • Fakultni nemocnice Motol a Homolka /ID# 251955
• France
  • Paris, France, 75015
    • AP-HP - Hopital Necker /ID# 251658
  • Paris, France, 75019
    • Hopitaux de Paris (AP-HP) - Hopital Robert Debre - CHU /ID# 252069
  • Toulouse, France, 31059
    • CHU Toulouse - Hopital Paule de Viguier /ID# 252070
  • New Aquitaine
    • Bordeaux, New Aquitaine, France, 33076
      • CHU Bordeaux - Hopital Pellegrin /ID# 253182
  • Rhone
    • Bron, Rhone, France, 69500
      • Hospices Civils de Lyon - Hôpital Femme Mère Enfant /ID# 251502
• Germany
  • Berlin, Germany, 13353
    • Charite Universitaetsmedizin Berlin Campus Virchow-Klinikum /ID# 251434
  • Bavaria
    • Munich, Bavaria, Germany, 80337
      • Dr. von Haunerschen Kinderspital /ID# 251440
  • North Rhine-Westphalia
    • Münster, North Rhine-Westphalia, Germany, 48149
      • Universitaetsklinikum Muenster /ID# 256763
  • Saxony
    • Leipzig, Saxony, Germany, 04129
      • Klinikum St. Georg gGmbH /ID# 262481
• Greece
  • Attica
    • Athens, Attica, Greece, 11527
      • Agia Sofia Hospital /ID# 250697
  • Crete
    • Heraklion, Crete, Greece, 71500
      • University General Hospital of Heraklion PA.G.N.I /ID# 250696
• Hungary
  • Budapest, Hungary, 1085
    • Semmelweis Egyetem /ID# 251083
  • Hajdú-Bihar
    • Debrecen, Hajdú-Bihar, Hungary, 4032
      • Debreceni Egyetem-Klinikai Kozpont /ID# 251835
• Israel
  • Central District
    • Petah Tikva, Central District, Israel, 4920235
      • Schneider Children's Medical Center /ID# 254833
  • Jerusalem
    • Jerusalem, Jerusalem, Israel, 91031
      • Shaare Zedek Medical Center /ID# 254832
• Italy
  • Bologna, Italy, 40133
    • Ospedale Maggiore Carlo Alberto Pizzardi /ID# 251626
  • Firenze
    • Florence, Firenze, Italy, 50139
      • Azienda Ospedaliero Universitaria Meyer /ID# 251624
  • Roma
    • Rome, Roma, Italy, 00161
      • Azienda Ospedaliero-Universitaria Policlinico Umberto I /ID# 251625
• Japan
  • Chiba
    • Kashiwa-shi, Chiba, Japan, 277-0871
      • Tsujinaka Hospital - Kashiwanoha /ID# 251930
  • Fukuoka
    • Kurume-shi, Fukuoka, Japan, 830-0011
      • Kurume University Hospital /ID# 251927
  • Hokkaido
    • Sapporo, Hokkaido, Japan, 060-0033
      • Hokkaido P.W.F.A.C. Sapporo-Kosei General Hospital /ID# 251928
  • Miyagi
    • Sendai, Miyagi, Japan, 989-3126
      • Miyagi Children's Hospital /ID# 251931
  • Osaka
    • Izumi-Shi, Osaka, Japan, 594-1101
      • Osaka Women's and Children's Hospital /ID# 252397
    • Osaka, Osaka, Japan, 558-8558
      • Osaka General Medical Center /ID# 253678
  • Saitama
    • Saitama-shi, Saitama, Japan, 330-8777
      • Saitama Children's Medical Center /ID# 252362
  • Tokyo
    • Bunkyo-ku, Tokyo, Japan, 113-8519
      • Institute of Science Tokyo Hospital /ID# 251929
    • Fuchu-shi, Tokyo, Japan, 183-8561
      • Tokyo Metropolitan Children's Medical Center /ID# 252477
    • Setagaya City, Tokyo, Japan, 157-8535
      • National Center For Child Health And Development /ID# 251926
• Mexico
  • Nuevo León
    • San Pedro Garza García, Nuevo León, Mexico, 66220
      • Servicios de Oncologia Medica Integral SA de CV /ID# 252974
• Netherlands
  • Groningen, Netherlands, 9713 GZ
    • Universitair Medisch Centrum Groningen /ID# 252003
  • North Holland
    • Amsterdam, North Holland, Netherlands, 1105 AZ
      • Amsterdam UMC, locatie AMC /ID# 250845
• New Zealand
  • Auckland, New Zealand, 0629
    • Starship Child Health /ID# 254702
  • Canterbury
    • Christchurch, Canterbury, New Zealand, 8011
      • Christchurch Hospital. /ID# 254703
• Poland
  • Kuyavian-Pomeranian Voivodeship
    • Torun, Kuyavian-Pomeranian Voivodeship, Poland, 87-100
      • Gastromed Sp. z o.o /ID# 251290
  • Masovian Voivodeship
    • Warsaw, Masovian Voivodeship, Poland, 04-730
      • Instytut Pomnik - Centrum Zdrowia Dziecka /ID# 251289
• Puerto Rico
  • San Juan, Puerto Rico, 00909-1711
    • Clinical Research Puerto Rico /ID# 266477
• South Korea
  • Daegu, South Korea, 41404
    • Kyungpook National University Chilgok Hospital /ID# 252663
  • Seoul Teugbyeolsi
    • Seoul, Seoul Teugbyeolsi, South Korea, 03080
      • Seoul National University Hospital /ID# 252024
    • Seoul, Seoul Teugbyeolsi, South Korea, 06351
      • Samsung Medical Center /ID# 252023
• Spain
  • Barcelona, Spain, 08035
    • Hospital Universitario Vall de Hebron /ID# 252104
  • Málaga, Spain, 29011
    • Hospital Regional Universitario de Malaga /ID# 251193
  • A Coruna
    • Ferrol, A Coruna, Spain, 15405
      • Hospital Arquitecto Marcide - Complejo Hospitalario Universitario de Ferrol /ID# 252105
  • Barcelona
    • Esplugues de Llobregat, Barcelona, Spain, 08950
      • Hospital Sant Joan de Deu /ID# 251194
• Taiwan
  • Taipei, Taiwan, 100
    • National Taiwan University Hospital /ID# 251650
  • Taoyuan City, Taiwan, 333
    • Linkou Chang Gung Memorial Hospital /ID# 251654
• United Kingdom
  • Birmingham, United Kingdom, B4 6NH
    • Birmingham Women's and Children's NHS Foundation Trust /ID# 253072
  • England
    • Sheffield, England, United Kingdom, S10 2TH
      • Sheffield Children's Hospital NHS Foundation Trust /ID# 251600
  • Greater London
    • London, Greater London, United Kingdom, E1 2ES
      • Disc_Barts Health NHS Trust - The Royal London Hospital /ID# 251917
    • London, Greater London, United Kingdom, WC1N 3HZ
      • Great Ormond Street Children's Hospital /ID# 252126
  • Hampshire
    • Southampton, Hampshire, United Kingdom, SO16 6YD
      • University Hospital Southampton NHS Foundation Trust /ID# 252097
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85016-7710
      • Phoenix Children's Hospital /ID# 250135
  • Arkansas
    • Little Rock, Arkansas, United States, 72202
      • Arkansas Children's Hospital /ID# 250106
  • California
    • Corona, California, United States, 92879-3104
      • Kindred Medical Institute - Corona /ID# 255484
    • Oakland, California, United States, 94609
      • UCSF Benioff Children's Hospital - Oakland /ID# 255067
    • Palo Alto, California, United States, 94304
      • Lucile Packard Children's Hospital /ID# 258430
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Children's Hospital Colorado - Aurora /ID# 250110
  • Delaware
    • Wilmington, Delaware, United States, 19803
      • Nemours/Alfred duPont Hospital for Children /ID# 255483
  • Georgia
    • Atlanta, Georgia, United States, 30329
      • Childrens Healthcare of Atlanta - Center for Advanced Pediatrics /ID# 255069
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Ann & Robert H. Lurie Children's Hospital of Chicago /ID# 254505
    • Peoria, Illinois, United States, 61637-0001
      • OSF St. Francis Medical Center /ID# 256968
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital /ID# 250142
    • Boston, Massachusetts, United States, 02115
      • Boston Children's Hospital /ID# 250108
  • New York
    • Mineola, New York, United States, 11501
      • NYU Langone Hospital - Long Island /ID# 250136
    • New York, New York, United States, 10029
      • The Mount Sinai Hospital /ID# 250141
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27514-4220
      • Univ NC Chapel Hill /ID# 254541
    • Charlotte, North Carolina, United States, 28203
      • Levine Children's Hospital /ID# 250131
  • Ohio
    • Cleveland, Ohio, United States, 44106
      • UH Cleveland Medical Center /ID# 250134
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104-4319
      • Children's Hospital of Philadelphia - Main /ID# 258773
  • Virginia
    • Norfolk, Virginia, United States, 23507
      • Children's Specialty Group /ID# 256966
  • Wisconsin
    • Madison, Wisconsin, United States, 53715-1218
      • University of Wisconsin - Madison /ID# 250632

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 years to 17 years (Child)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Quadruple

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Period 1- Open Label Induction Phase; All participants in open label induction phase of Period 1 will receive upadacitinib Dose A for 8 weeks based on body weight.	Drug: Upadacitinib; Oral Solution/ Tablets; Other Names: RINVOQ
Experimental: Period 1- Double Blind Maintenance Phase; 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.	Drug: Upadacitinib; Oral Solution/ Tablets; Other Names: RINVOQ
Experimental: Period 2- Open Label Long Term Extension Phase Arm A; 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.	Drug: Upadacitinib; Oral Solution/ Tablets; Other Names: RINVOQ
Experimental: Period 2- Open Label Long Term Extension Phase Arm B; 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.	Drug: Upadacitinib; Oral Solution/ Tablets; Other Names: RINVOQ
Experimental: Period 2- Long Term Extension Phase Arm C; Clinical responders who complete Period 1 through Week 52 will receive upadacitinib Dose C daily for up to 260 weeks in OLE Period 2.	Drug: Upadacitinib; Oral Solution/ Tablets; Other Names: RINVOQ

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Achieving Adapted Mayo score (AMS) Clinical Remission (Period 1)	The Mayo score is a tool designed to measure disease activity for ulcerative colitis. The AMS is a composite of the following subscores: stool frequency subscore (SFS), rectal bleeding subscore (RBS) and endoscopy subscore (MES). AMS ranges from 0 to 9 where higher scores represent more severe disease. Clinical remission is defined as an AMS < or = 2, with SFS < or = 1 and not higher than baseline, RBS of 0, and MES < or = 1.	Week 8
Percentage of Participants Achieving AMS Clinical Remission Among Week 8 Responders per AMS (Period 1)	The Mayo score is a tool designed to measure disease activity for ulcerative colitis. AMS ranges from 0 to 9 where higher scores represent more severe disease. Clinical remission is defined as an AMS ≤ 2, with SFS ≤ 1 and not higher than Baseline, RBS of 0, and MES ≤ 1.	Week 52

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Achieving Endoscopic Improvement (Period 1)	Endoscopic Improvement is defined as MES < or = 1.	Week 8
Percentage of Participants Achieving Partial Mayo Score (PMS) Clinical Remission (Period 1)	The Mayo score is a tool designed to measure disease activity for ulcerative colitis. The PMS is a composite of the following subscores: SFS, RBS and physician's global assessment (PGA). The PMS ranges from 0 to 9 with higher scores representing more severe disease. PMS clinical remission is defined as a PMS < or = 2 and no individual subscore > 1.	Week 8
Percentage of Participants Achieving AMS Clinical Response (Period 1)	The adapted mayo score (AMS) is a composite of the following subscores: SFS, RBS and MES. AMS clinical response is defined as decrease in AMS by > or = 2 points and > or = 30% from baseline with a decrease in RBS of > or = 1 or an absolute RBS of 0 or 1.	Week 8
Percentage of Participants Achieving Endoscopic Improvement Among Week 8 Responders per AMS (Period 1)	Endoscopic Improvement is defined as MES of < or = 1. The AMS is a composite of the following subscores: SFS, RBS and MES.	Week 52
Percentage of Participants Achieving PMS Clinical Remission Among Week 8 Responders per AMS (Period 1)	The Mayo score is a tool designed to measure disease activity for ulcerative colitis. The PMS ranges from 0 to 9 with higher scores representing more severe disease. PMS clinical remission is defined as a PMS < or = 2 and no individual subscore > 1. The AMS is a composite of the following subscores: SFS, RBS and MES.	Week 52
Percentage of Participants Achieving AMS Clinical Response Among Week 8 Responders per AMS (Period 1)	The AMS is a composite of the following subscores: SFS, RBS and MES. AMS clinical response is defined as decrease in AMS by > or = 2 points and > or = 30% from baseline with a decrease in RBS of > or = 1 or an absolute RBS of 0 or 1.	Week 52
Percentage of Participants Achieving PMS Clinical Response Among Week 8 Clinical Responders per AMS (Period 1)	The AMS is a composite of the following subscores: SFS, RBS and endoscopy MES. PMS clinical response is defined as decrease in PMS by > or = 2 points and > or = 30% from baseline with a decrease in RBS > or = 1 or an absolute RBS of 0 or 1.	Week 52
Percentage of Participants Achieving Corticosteroid-Free AMS Clinical Remission Among Week 8 Responders per AMS (Period 1)	Corticosteroid-free AMS clinical remission is defined as being in AMS clinical remission and free of corticosteroids for >= 90 days immediately preceeding the timepoint of endpoint assessment. The AMS is a composite of the following subscores: SFS, RBS and MES.	Week 52
Percentage of Participants Achieving AMS Clinical Remission Among Week 8 Remitters per AMS (Period 1)	The AMS is a composite of the following subscores: SFS, RBS and MES. Adapted Mayo score ranges from 0 to 9 where higher scores represent more severe disease. Clinical remission is defined as an AMS < or = 2, with SFS < or = 1 and not higher than baseline, RBS of 0, and MES < or = 1.	Week 52

Collaborators and Investigators

• Sponsor: AbbVie
• Investigators: Study Director: ABBVIE INC., AbbVie

Publications and helpful links

Helpful Links

• This clinical study may be evaluating a usage that is not currently FDA approved. Please see US Prescribing Information for approved uses.

Study record dates

Study Major Dates

• Study Start (Actual): November 6, 2023
• Primary Completion (Estimated): August 1, 2028
• Study Completion (Estimated): October 1, 2031

Study Registration Dates

• First Submitted: March 13, 2023
• First Submitted That Met QC Criteria: March 13, 2023
• First Posted (Actual): March 24, 2023

Study Record Updates

• Last Update Posted (Actual): May 14, 2026
• Last Update Submitted That Met QC Criteria: May 12, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Ulcerative Colitis; Upadacitinib; UC; RINVOQ; Corticosteroids; Biologic Therapy; Immunosuppressants
• Additional Relevant MeSH Terms: Intestinal Diseases; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Gastroenteritis; Inflammatory Bowel Diseases; Colitis; Colitis, Ulcerative; Janus Kinase Inhibitors; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antirheumatic Agents; Protein Kinase Inhibitors; upadacitinib
• Other Study ID Numbers: M14-658; 2022-501788-41-00 (Other Identifier: EU CT)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: AbbVie is committed to responsible clinical trial data sharing. This includes access to anonymized, individual and trial-level data (analysis data sets), as well as other information.
• IPD Sharing Time Frame: For details on when studies are available for sharing visit https://vivli.org/ourmember/abbvie/
• IPD Sharing Access Criteria: To learn more about the process, or to submit a request, visit the following link https://www.abbvieclinicaltrials.com/hcp/data-sharing/
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes