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.

Study Overview
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Brief Summary
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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 85 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.

Official Title
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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

Conditions
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Ulcerative Colitis

Intervention / Treatment
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* Drug: Upadacitinib


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 2 Years
Maximum Age: 17 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Period 1- Open Label Induction Phase<br>All participants in open label induction phase of Period 1 will receive upadacitinib Dose A for 8 weeks based on body weight. | Drug: Upadacitinib<br>* Oral Solution/ Tablets<br>* Other names: RINVOQ;|
| Experimental: Period 1- Double Blind Maintenance Phase<br>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<br>* Oral Solution/ Tablets<br>* Other names: RINVOQ;|
| Experimental: Period 2- Open Label Long Term Extension Phase Arm A<br>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<br>* Oral Solution/ Tablets<br>* Other names: RINVOQ;|
| Experimental: Period 2- Open Label Long Term Extension Phase Arm B<br>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<br>* Oral Solution/ Tablets<br>* Other names: RINVOQ;|
| Experimental: Period 2- Long Term Extension Phase Arm C<br>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<br>* Oral Solution/ Tablets<br>* Other names: RINVOQ;|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Upadacitinib, RINVOQ, Ulcerative Colitis, UC, Corticosteroids, Immunosuppressants, Biologic Therapy