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

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

Overview

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.

Interventions

• Drug Upadacitinib
  Oral Solution/ Extended-Release Tablets

Primary outcome measures

• 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 [Time frame: At Week 64]
• Achievement of endoscopic response at Week 64 in participants who achieved clinical response per PCDAI at Week 12. [Time frame: At Week 64]
• Number of Participants with Adverse Events [Time frame: Through Week 156]

Secondary outcome measures (7)

• Achievement of clinical remission per PCDAI [Time frame: Week 12]
• Achievement of endoscopic response [Time frame: Week 12]
• Achievement of endoscopic remission [Time frame: Week 12]
• Achievement of clinical response per PCDAI [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 [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 [Time frame: Week 64]

Eligibility criteria

Inclusion criteria

• Weight at Screening and Baseline must be >= 10 kg
• Moderate to severe Crohn's Disease (CD) defined as Pediatric Crohn's Disease Activity Index (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, immunomodulators (IMMs), and/or biologic therapy or in whom use of those therapies is medically contraindicated. For participants in the US and South Korea, participants must have demonstrated an inadequate response, loss of 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 ulcerative colitis (UC), indeterminate colitis, or monogenic inflammatory bowel disease (IBD);
• Fulminant colitis or toxic megacolon;
• Gastrointestinal (GI) 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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Sequential

Masking

Quadruple blind

Primary purpose

Treatment

Study locations

United States · 12 centers

• UCSF Benioff Children's Hospital - Oakland /ID# 262217 — Oakland
• Lucile Packard Children's Hospital /ID# 262193 — Palo Alto
• Children's Hospital Colorado - Aurora /ID# 262207 — Aurora
• Connecticut Children's Medical Center - Hartford /ID# 262256 — Hartford
• OSF St. Francis Medical Center /ID# 262192 — Peoria
• Indiana University Health Riley Hospital for Children /ID# 262215 — Indianapolis
• Boston Children's Hospital /ID# 262191 — Boston
• MNGI Digestive Health, P. A. /ID# 262204 — Minneapolis
• … and 4 more centers

China · 10 centers

• Beijing Children's Hospital /ID# 262258 — Beijing
• Guangzhou Medical University Affiliated Women and Children's Medical Center /ID# 262596 — Guangzhou
• The Sixth Affiliated Hospital of Sun Yat-sen University /ID# 272807 — Guangzhou
• Henan Children's Hospital Zhengzhou Children's Hospital /ID# 262300 — Zhengzhou
• Hunan Children's Hospital /ID# 262512 — Changsha
• Jiangxi Provincial Children's Hospital /ID# 262295 — Nanchang
• Shengjing Hospital of China Medical University /ID# 262301 — Shenyang
• Children's Hospital of Shanghai /ID# 262356 — Shanghai
• … and 2 more centers

Japan · 10 centers

• Tsujinaka Hospital - Kashiwanoha /ID# 262454 — Kashiwa-shi
• Kurume University Hospital /ID# 262455 — Kurume-shi
• Miyagi Children's Hospital /ID# 262459 — Sendai
• Osaka Women's and Children's Hospital /ID# 262549 — Izumi-Shi
• Saga University Hospital /ID# 262753 — Saga
• Saitama Children's Medical Center /ID# 262461 — Saitama-shi
• Institute of Science Tokyo Hospital /ID# 262510 — Bunkyo-ku
• Tokyo Metropolitan Children's Medical Center /ID# 262550 — Fuchu-shi
• … and 2 more centers

Belgium · 6 centers

• Uza /Id# 261745 — Edegem
• Cliniques Universitaires UCL Saint-Luc /ID# 261741 — Brussels
• Universitair Ziekenhuis Leuven /ID# 261740 — Leuven
• Hospital Universite Enfants Reine Fabiola /ID# 261744 — Brussels
• CHR de la Citadelle /ID# 261749 — Liège
• UCL Namur University Hospital, Site Sainte-Elisabeth /ID# 261750 — Namur

Australia · 5 centers

• Sydney Children's Hospital /ID# 262352 — Randwick
• Children's Hospital at Westmead /ID# 262350 — Westmead
• Queensland Children's Hospital /ID# 262351 — South Brisbane
• Monash Health - Monash Medical Centre - Clayton /ID# 262878 — Clayton
• Perth Children'S Hospital /ID# 272905 — Perth

Brazil · 5 centers

• Galileo Medical Research Ltda /ID# 262602 — Juiz de Fora
• Hospital Pequeno Príncipe /ID# 262600 — Curitiba
• Santo Antônio Children's Hospital /ID# 262601 — Porto Alegre
• Rocco & Nazato Servicos Medicos /ID# 262485 — São Paulo
• Hospital Sirio Libanes - Sao Paulo /ID# 262670 — São Paulo

Spain · 5 centers

• Hospital Arquitecto Marcide - Complejo Hospitalario Universitario de Ferrol /ID# 262226 — Ferrol
• Hospital Sant Joan de Deu /ID# 262599 — Esplugues de Llobregat
• Hospital Regional Universitario de Malaga /ID# 262228 — Málaga
• Hospital Universitario Virgen del Rocio /ID# 262712 — Seville
• Hospital Clinico Universitario Lozano Blesa /ID# 262227 — Zaragoza

United Kingdom · 5 centers

Center list to be confirmed — check the primary protocol.

Italy · 4 centers

• Fondazione di Religione e di Culto Casa Sollievo della Sofferenza /ID# 262384 — San Giovanni Rotondo
• Ospedale Pediatrico Bambino Gesù /ID# 262379 — Rome
• Azienda Ospedaliera Universitaria Gaetano Martino /ID# 262380 — Messina
• Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico /ID# 275276 — Milan

Canada · 3 centers

• BC Children's Hospital /ID# 262237 — Vancouver
• IWK Health Center /ID# 262543 — Halifax
• CHU Sainte-Justine /ID# 262096 — Montreal

France · 3 centers

• CHU de CAEN - Hopital de la Cote de Nacre /ID# 262311 — Caen
• Hospices Civils de Lyon - Hôpital Femme Mère Enfant /ID# 263422 — Bron
• Hopitaux de Paris (AP-HP) - Hopital Robert Debre - CHU /ID# 262308 — Paris

Greece · 3 centers

• Agia Sofia Hospital /ID# 261792 — Athens
• General Hospital of Chest Diseases of Athens SOTIRIA /ID# 261790 — Athens
• University General Hospital of Heraklion PA.G.N.I /ID# 261791 — Heraklion

Puerto Rico · 3 centers

• Clinical Research Investigator Group /ID# 262357 — Bayamón
• Puerto Rico Health Institute /ID# 262358 — Dorado
• Clinical Research Puerto Rico /ID# 279595 — San Juan

South Korea · 3 centers

• Seoul National University Hospital /ID# 262324 — Seoul
• Yonsei University Health System Severance Hospital /ID# 262721 — Seoul
• Samsung Medical Center /ID# 262323 — Seoul

Bulgaria · 2 centers

• UMHAT Sveti Georgi /ID# 262590 — Plovdiv
• Specialized Hospital For Active Treatment Of Children Diseases Prof. Ivan Mitev /ID# 26258 — Sofia

New Zealand · 2 centers

• Starship Child Health /ID# 262576 — Grafton
• Christchurch Hospital. /ID# 262577 — Christchurch

Poland · 2 centers

• Gastromed Sp. z o.o /ID# 262367 — Torun
• Instytut Pomnik - Centrum Zdrowia Dziecka /ID# 262366 — Warsaw

Taiwan · 2 centers

• National Taiwan University Hospital /ID# 261695 — Taipei
• Linkou Chang Gung Memorial Hospital /ID# 261696 — Taoyuan City

Identifiers

NCT: NCT06332534 · M14-671 · 2023-509618-12

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗