Clinical trial NCT06332534: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Crohn's Disease
Keywords: Crohn's Disease
Upadacitinib
RINVOQ
Lead sponsor: AbbVie
Sponsor class: INDUSTRY
First posted: 2024-03-27
Enrollment: 110
Sex: ALL
Minimum age (years): 2
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: 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
timeFrame: At Week 64
measure: Achievement of endoscopic response at Week 64 in participants who achieved clinical response per PCDAI at Week 12.
timeFrame: At Week 64
measure: Number of Participants with Adverse Events
timeFrame: Through Week 156
Secondary outcomes:
measure: Achievement of clinical remission per PCDAI
timeFrame: Week 12
measure: Achievement of endoscopic response
timeFrame: Week 12
measure: Achievement of endoscopic remission
timeFrame: Week 12
measure: Achievement of clinical response per PCDAI
timeFrame: Week 12
measure: Achievement of clinical response per PCDAI at Week 64 in participants who achieved clinical response per PCDAI at Week 12
timeFrame: Week 64
measure: Achievement of endoscopic remission at Week 64 in participants who achieved clinical response per PCDAI at Week 12
timeFrame: Week 64
measure: Achievement of corticosteroid (CS)-free clinical remission per PCDAI at Week 64 in participants who achieved clinical response per PCDAI at Week 12
timeFrame: Week 64
Other outcomes:
Locations:
city: Oakland
country: United States
facility: UCSF Benioff Children's Hospital - Oakland /ID# 262217
state: California
city: Aurora
country: United States
facility: Children's Hospital Colorado - Aurora /ID# 262207
state: Colorado
city: Hartford
country: United States
facility: Connecticut Children's Medical Center - Hartford /ID# 262256
state: Connecticut
city: Peoria
country: United States
facility: OSF St. Francis Medical Center /ID# 262192
state: Illinois
city: Indianapolis
country: United States
facility: Indiana University Health Riley Hospital for Children /ID# 262215
state: Indiana
city: Minneapolis
country: United States
facility: MNGI Digestive Health, P. A. /ID# 262204
state: Minnesota
city: New York
country: United States
facility: Icahn School of Medicine at Mount Sinai /ID# 262216
state: New York
city: Chapel Hill
country: United States
facility: Univ NC Chapel Hill /ID# 262198
state: North Carolina
city: Cleveland
country: United States
facility: UH Cleveland Medical Center /ID# 262188
state: Ohio
city: Philadelphia
country: United States
facility: Children's Hospital of Philadelphia - Main /ID# 262197
state: Pennsylvania
city: Randwick
country: Australia
facility: Sydney Children's Hospital /ID# 262352
state: New South Wales
city: Westmead
country: Australia
facility: Children's Hospital at Westmead /ID# 262350
state: New South Wales
city: South Brisbane
country: Australia
facility: Queensland Children's Hospital /ID# 262351
state: Queensland
city: Clayton
country: Australia
facility: Monash Health - Monash Medical Centre /ID# 262878
state: Victoria
city: Perth
country: Australia
facility: Perth Children'S Hospital /ID# 272905
state: Western Australia
city: Edegem
country: Belgium
facility: Uza /Id# 261745
state: Antwerpen
city: Bruxelles
country: Belgium
facility: Cliniques Universitaires UCL Saint-Luc /ID# 261741
state: Bruxelles-Capitale
city: Leuven
country: Belgium
facility: Universitair Ziekenhuis Leuven /ID# 261740
state: Vlaams-Brabant
city: Bruxelles
country: Belgium
facility: Hospital Universite Enfants Reine Fabiola /ID# 261744
city: Liege
country: Belgium
facility: CHR de la Citadelle /ID# 261749
city: Namur
country: Belgium
facility: UCL Namur University Hospital, Site Sainte-Elisabeth /ID# 261750
city: Juiz de Fora
country: Brazil
facility: Galileo Medical Research Ltda /ID# 262602
state: Minas Gerais
city: Curitiba
country: Brazil
facility: Hospital Pequeno Príncipe /ID# 262600
state: Parana
city: Porto Alegre
country: Brazil
facility: Irmandade da Santa Casa de Misericordia de Porto Alegre /ID# 262601
state: Rio Grande Do Sul
city: São Paulo
country: Brazil
facility: Hospital Sírio Libanês /ID# 262670
state: Sao Paulo
city: São Paulo
country: Brazil
facility: Rocco & Nazato Servicos Medicos /ID# 262485
state: Sao Paulo
city: Plovdiv
country: Bulgaria
facility: UMHAT Sveti Georgi /ID# 262590
city: Sofiya
country: Bulgaria
facility: Specialized Hospital For Active Treatment Of Children Diseases Prof. Ivan Mitev /ID# 262589
city: Beijing
country: China
facility: Beijing Children's Hospital /ID# 262258
state: Beijing
city: Guangzhou
country: China
facility: Guangzhou Medical University Affiliated Women and Children's Medical Center /ID# 262596
state: Guangdong
city: Guangzhou
country: China
facility: The Sixth Affiliated Hospital of Sun Yat-sen University /ID# 272807
state: Guangdong
city: Zhengzhou
country: China
facility: Henan Children's Hospital Zhengzhou Children's Hospital /ID# 262300
state: Henan
city: Changsha
country: China
facility: Hunan Children's Hospital /ID# 262512
state: Hunan
city: Shenyang
country: China
facility: Shengjing Hospital of China Medical University /ID# 262301
state: Liaoning
city: Shanghai
country: China
facility: Children's Hospital of Shanghai /ID# 262356
state: Shanghai
city: Shanghai
country: China
facility: Ruijin Hospital, Shanghai Jiaotong University School of Medicine /ID# 262502
state: Shanghai
city: Bron
country: France
facility: Hospices Civils de Lyon - Hôpital Femme Mère Enfant /ID# 263422
state: Rhone
city: Caen
country: France
facility: CHU de CAEN - Hopital de la Cote de Nacre /ID# 262311
city: Paris
country: France
facility: Hopitaux de Paris (AP-HP) - Hopital Robert Debre - CHU /ID# 262308
city: Athens
country: Greece
facility: Agia Sofia Hospital /ID# 261792
state: Attiki
city: Athens
country: Greece
facility: General Hospital of Chest Diseases of Athens SOTIRIA /ID# 261790
state: Attiki
city: Heraklion
country: Greece
facility: University General Hospital of Heraklion PA.G.N.I /ID# 261791
state: Kriti
city: San Giovanni Rotondo
country: Italy
facility: Fondazione di Religione e di Culto Casa Sollievo della Sofferenza /ID# 262384
state: Foggia
city: Messina
country: Italy
facility: Azienda Ospedaliera Universitaria Gaetano Martino /ID# 262380
city: Kashiwa-shi
country: Japan
facility: Tsujinaka Hospital Kashiwanoha /ID# 262454
state: Chiba
city: Kurume-shi
country: Japan
facility: Kurume University Hospital /ID# 262455
state: Fukuoka
city: Sendai-shi
country: Japan
facility: Miyagi Children's Hospital /ID# 262459
state: Miyagi
city: Izumi-Shi
country: Japan
facility: Osaka Women's and Children's Hospital /ID# 262549
state: Osaka
city: Saga-shi
country: Japan
facility: Saga University Hospital /ID# 262753
state: Saga
city: Saitama-shi
country: Japan
facility: Saitama Children's Medical Center /ID# 262461
state: Saitama
city: Bunkyo-ku
country: Japan
facility: Institute of Science Tokyo Hospital /ID# 262510
state: Tokyo
city: Fuchu-shi
country: Japan
facility: Tokyo Metropolitan Children's Medical Center /ID# 262550
state: Tokyo
city: Setagaya-ku
country: Japan
facility: National Center for Child Health and Development /ID# 262456
state: Tokyo
city: Toyama-shi
country: Japan
facility: Toyama Prefectural Central Hospital /ID# 262739
state: Toyama
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital /ID# 262324
state: Seoul Teugbyeolsi
city: Seoul
country: Korea, Republic of
facility: Yonsei University Health System Severance Hospital /ID# 262721
state: Seoul Teugbyeolsi
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center /ID# 262323
state: Seoul Teugbyeolsi
city: Christchurch
country: New Zealand
facility: Christchurch Hospital /ID# 262577
state: Canterbury
city: Auckland
country: New Zealand
facility: Starship Child Health /ID# 262576
city: Torun
country: Poland
facility: Gastromed Sp. z o.o /ID# 262367
state: Kujawsko-pomorskie
city: Warszawa
country: Poland
facility: Instytut Pomnik - Centrum Zdrowia Dziecka /ID# 262366
state: Mazowieckie
city: Bayamon
country: Puerto Rico
facility: Clinical Research Investigator Group, LLC /ID# 262357
city: Dorado
country: Puerto Rico
facility: Puerto Rico Health Institute /ID# 262358
city: Ferrol
country: Spain
facility: Hospital Arquitecto Marcide - Complejo Hospitalario Universitario de Ferrol /ID# 262226
state: A Coruna
city: Esplugues de Llobregat
country: Spain
facility: Hospital Sant Joan de Deu /ID# 262599
state: Barcelona
city: Malaga
country: Spain
facility: Hospital Regional Universitario de Malaga /ID# 262228
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen del Rocio /ID# 262712
city: Zaragoza
country: Spain
facility: Hospital Clinico Universitario Lozano Blesa /ID# 262227
city: Taipei City
country: Taiwan
facility: National Taiwan University Hospital /ID# 261695
state: Taipei
city: Taoyuan City
country: Taiwan
facility: Linkou Chang Gung Memorial Hospital /ID# 261696
city: Cambridge
country: United Kingdom
facility: Addenbrooke's Hospital /ID# 262707
state: Cambridgeshire
city: Sheffield
country: United Kingdom
facility: Sheffield Children's Hospital NHS Foundation Trust /ID# 261832
state: England
city: London
country: United Kingdom
facility: Barts Health NHS Trust /ID# 262811
state: Greater London
city: Norwich
country: United Kingdom
facility: Norfolk and Norwich University Hospitals NHS Foundation Trust /ID# 262778
state: Norfolk
city: Edinburgh
country: United Kingdom
facility: Royal Hospital for Children and Young People /ID# 262388
Study officials:
affiliation: AbbVie
name: ABBVIE INC.
role: STUDY_DIRECTOR
References: