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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT06332534




Registration number
NCT06332534
Ethics application status
Date submitted
19/03/2024
Date registered
27/03/2024
Date last updated
26/08/2024

Titles & IDs
Public title
Crohn's Disease: Efficacy, Safety, and Pharmacokinetics of Upadacitinib in Pediatric Subjects With Moderately to Severely Active Crohn's Disease
Scientific 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
Secondary ID [1] 0 0
M14-671
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Crohn's Disease 0 0
Condition category
Condition code
Oral and Gastrointestinal 0 0 0 0
Inflammatory bowel disease
Inflammatory and Immune System 0 0 0 0
Other inflammatory or immune system disorders
Oral and Gastrointestinal 0 0 0 0
Crohn's disease

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Upadacitinib

Experimental: Period 1: Open Label Induction Phase (Dose A) - All participants in the open label induction phase of Period 1 will receive upadacitinib Dose A for 12 weeks based on body weight.

Experimental: Period 1: Double-Blind Maintenance Phase (Dose B) - Clinical responders per PCDAI at the end of open label induction phase of Period 1 will be randomly assigned to receive Dose B or C for 52 weeks (oral solution dose will be based on body weight)

Experimental: Period 1: Double-Blind Maintenance Phase (Dose C) - Clinical responders per PCDAI at the end of open label induction phase of Period 1 will be randomly assigned to receive either upadacitinib Dose C or B for 52 weeks (oral solution dose will be based on body weight)

Experimental: Period 2: Open Label Long-Term Extension Phase Cohort 1 - Participants receiving double-blind maintenance therapy with upadacitinib Dose B or upadacitinib Dose C daily in Period 1 who complete the Week 64 visit will receive upadacitinib Dose B daily for up to 156 weeks.

Experimental: Period 2: Open Label Long-Term Extension Phase Cohort 2 - Participants who were receiving rescue therapy with open-label upadacitinib Dose C during maintenance phase in Period 1 and completed the Week 64 visit will continue to receive upadacitinib Dose C daily for up to 156 weeks.

Experimental: Period 2: Open Label Long-Term Extension Phase Cohort 3 - Participants who did not achieve clinical response per PCDAI at Week 12 of Period 1 will receive an extended treatment with open-label upadacitinib Dose C daily for an additional 12 weeks. If they are responders after 12 weeks extended treatment, they will continue, otherwise they may be discontinued at the discretion of the investigator


Treatment: Drugs: Upadacitinib
Oral Solution/ Extended-Release Tablets
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
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
Timepoint [1] 0 0
At Week 64
Primary outcome [2] 0 0
Achievement of endoscopic response at Week 64 in participants who achieved clinical response per PCDAI at Week 12.
Timepoint [2] 0 0
At Week 64
Primary outcome [3] 0 0
Number of Participants with Adverse Events
Timepoint [3] 0 0
Through Week 156
Secondary outcome [1] 0 0
Achievement of clinical remission per PCDAI
Timepoint [1] 0 0
Week 12
Secondary outcome [2] 0 0
Achievement of endoscopic response
Timepoint [2] 0 0
Week 12
Secondary outcome [3] 0 0
Achievement of endoscopic remission
Timepoint [3] 0 0
Week 12
Secondary outcome [4] 0 0
Achievement of clinical response per PCDAI
Timepoint [4] 0 0
Week 12
Secondary outcome [5] 0 0
Achievement of clinical response per PCDAI at Week 64 in participants who achieved clinical response per PCDAI at Week 12
Timepoint [5] 0 0
Week 64
Secondary outcome [6] 0 0
Achievement of endoscopic remission at Week 64 in participants who achieved clinical response per PCDAI at Week 12
Timepoint [6] 0 0
Week 64
Secondary outcome [7] 0 0
Achievement of corticosteroid (CS)-free clinical remission per PCDAI at Week 64 in participants who achieved clinical response per PCDAI at Week 12
Timepoint [7] 0 0
Week 64

Eligibility
Key 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).
Minimum age
2 Years
Maximum age
17 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Other
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
26/07/2024
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
20/12/2034
Actual
Sample size
Target
110
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NT
Recruitment hospital [1] 0 0
Children's Hospital at Westmead /ID# 262350 - Westmead
Recruitment postcode(s) [1] 0 0
2145 - Westmead
Recruitment outside Australia
Country [1] 0 0
Japan
State/province [1] 0 0
Chiba
Country [2] 0 0
Japan
State/province [2] 0 0
Fukuoka
Country [3] 0 0
Japan
State/province [3] 0 0
Miyagi
Country [4] 0 0
Japan
State/province [4] 0 0
Osaka
Country [5] 0 0
Japan
State/province [5] 0 0
Saga
Country [6] 0 0
Japan
State/province [6] 0 0
Saitama
Country [7] 0 0
Japan
State/province [7] 0 0
Tokyo
Country [8] 0 0
Japan
State/province [8] 0 0
Toyama
Country [9] 0 0
Korea, Republic of
State/province [9] 0 0
Seoul Teugbyeolsi
Country [10] 0 0
New Zealand
State/province [10] 0 0
Canterbury
Country [11] 0 0
Puerto Rico
State/province [11] 0 0
Bayamon
Country [12] 0 0
Puerto Rico
State/province [12] 0 0
Dorado
Country [13] 0 0
Taiwan
State/province [13] 0 0
Taipei

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
AbbVie
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/study/NCT06332534
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
ABBVIE INC.
Address 0 0
AbbVie
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
ABBVIE CALL CENTER
Address 0 0
Country 0 0
Phone 0 0
844-663-3742
Fax 0 0
Email 0 0
[email protected]
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT06332534