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.

Sponsor

AbbVie (Industry)

Overall Status

Not yet recruiting

CT.gov ID

NCT05782907

Collaborator

(none)

110

Enrollment

Locations

Arms

64.1

Anticipated Duration (Months)

1.7

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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 75 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.

Condition or Disease	Intervention/Treatment	Phase
Ulcerative Colitis	Drug: Upadacitinib	Phase 3

Study Design

Study Type:

Interventional

Anticipated Enrollment :

110 participants

Allocation:

Randomized

Intervention Model:

Sequential Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

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

Anticipated Study Start Date :

May 11, 2023

Anticipated Primary Completion Date :

Aug 12, 2028

Anticipated Study Completion Date :

Sep 12, 2028

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

Percentage of Participants Achieving Adapted Mayo score (AMS) Clinical Remission (Period 1) [Week 8]
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.
Percentage of Participants Achieving AMS Clinical Remission Among Week 8 Responders per AMS (Period 1) [Week 52]
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.

Secondary Outcome Measures

Percentage of Participants Achieving Endoscopic Improvement (Period 1) [Week 8]
Endoscopic Improvement is defined as MES < or = 1.
Percentage of Participants Achieving Partial Mayo Score (PMS) Clinical Remission (Period 1) [Week 8]
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.
Percentage of Participants Achieving AMS Clinical Response (Period 1) [Week 8]
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.
Percentage of Participants Achieving Endoscopic Improvement Among Week 8 Responders per AMS (Period 1) [Week 52]
Endoscopic Improvement is defined as MES of < or = 1. The AMS is a composite of the following subscores: SFS, RBS and MES.
Percentage of Participants Achieving PMS Clinical Remission Among Week 8 Responders per AMS (Period 1) [Week 52]
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.
Percentage of Participants Achieving AMS Clinical Response Among Week 8 Responders per AMS (Period 1) [Week 52]
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.
Percentage of Participants Achieving PMS Clinical Response Among Week 8 Clinical Responders per AMS (Period 1) [Week 52]
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.
Percentage of Participants Achieving Corticosteroid-Free AMS Clinical Remission Among Week 8 Responders per AMS (Period 1) [Week 52]
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.
Percentage of Participants Achieving AMS Clinical Remission Among Week 8 Remitters per AMS (Period 1) [Week 52]
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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

2 Years to 17 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Massachusetts General Hospital /ID# 250142	Boston	Massachusetts	United States	02114
2	Levine Children's Specialty Center- Charlotte /ID# 250131	Charlotte	North Carolina	United States	28203-5866
3	UH Cleveland Medical Center /ID# 250134	Cleveland	Ohio	United States	44106
4	Hospital Italiano de Buenos Aires /ID# 251796	Ciudad Autonoma Buenos Aires	Ciuadad Autonoma De Buenos Aires	Argentina	1199
5	Hospital Privado Univesitario /ID# 251902	Cordoba		Argentina	5016
6	Universitair Ziekenhuis Antwerpen /ID# 251184	Edegem	Antwerpen	Belgium	2650
7	Universitair Ziekenhuis Leuven /ID# 251185	Leuven	Vlaams-Brabant	Belgium	3000
8	Hospital Pequeno Princípe /ID# 251911	Curitiba	Parana	Brazil	80250-060
9	Hospital PUC-Campinas /ID# 251912	Campinas	Sao Paulo	Brazil	13060-904
10	Rocco e Nazato Serviços Médicos Ltda. /ID# 251910	Sao Paulo		Brazil	04543-001
11	UMHAT Sveti Georgi /ID# 251949	Plovdiv		Bulgaria	4002
12	Acibadem City Clinic Tokuda University Hospital EAD /ID# 251287	Sofia		Bulgaria	1407
13	Specialized Hospital For Active Treatment Of Children Diseases Prof. Ivan Mitev /ID# 251285	Sofiya		Bulgaria	1606
14	UMHAT Sveta Marina /ID# 251948	Varna		Bulgaria	9010
15	Alberta Health Services /ID# 252088	Edmonton	Alberta	Canada	T6G 1C9
16	BC Children's Hospital /ID# 250947	Vancouver	British Columbia	Canada	V6H 3V4
17	Fakultni nemocnice Plzen /ID# 253284	Plzen		Czechia	305 99
18	Fakultni Nemocnice v Motole /ID# 251955	Praha		Czechia	150 06
19	HCL - Hopital Lyon Sud /ID# 251502	Bron CEDEX	Rhone	France	69677
20	CHU Bordeaux - Hopital Pellegrin /ID# 253182	Bordeaux		France	33000
21	AP-HP - Hopital Necker /ID# 251658	Paris		France	75015
22	Robert Debre Hopital, FR /ID# 252069	Paris		France	75019
23	CHU Toulouse - Hopital Paule de Viguier /ID# 252070	Toulouse		France	31059
24	Agia Sofia Hospital /ID# 250697	Athens	Attiki	Greece	11527
25	University General Hospital of Heraklion PA.G.N.I /ID# 250696	Heraklion	Kriti	Greece	71500
26	Debreceni Egyetem Klinikai Kozpont /ID# 251835	Debrecen	Hajdu-Bihar	Hungary	4032
27	Semmelweis Egyetem /ID# 251083	Budapest		Hungary	1083
28	Azienda Ospedaliero Universitaria Meyer /ID# 251624	Florence	Firenze	Italy	50139
29	Azienda Ospedaliero-Universitaria Policlinico Umberto I /ID# 251625	Rome	Lazio	Italy	00161
30	Ospedale Maggiore Carlo Alberto Pizzardi /ID# 251626	Bologna		Italy	40133
31	Tsujinaka Hospital Kashiwanoha /ID# 251930	Kashiwa-shi	Chiba	Japan	277-0871
32	Kurume University Hospital /ID# 251927	Kurume-shi	Fukuoka	Japan	830-0011
33	Hokkaido P.W.F.A.C. Sapporo-Kosei General Hospital /ID# 251928	Sapporo-shi	Hokkaido	Japan	060-0033
34	Miyagi Children's Hospital /ID# 251931	Sendai-shi	Miyagi	Japan	989-3126
35	Osaka Women's and Children's Hospital /ID# 252397	Izumi-Shi	Osaka	Japan	594-1101
36	Osaka General Medical Center /ID# 253678	Osaka-shi	Osaka	Japan	558-8558
37	Saitama Children's Medical Center /ID# 252362	Saitama-shi	Saitama	Japan	330-8777
38	Tokyo Medical And Dental University Hospital /ID# 251929	Bunkyo-ku	Tokyo	Japan	113-8519
39	Tokyo Metropolitan Children's Medical Center /ID# 252477	Fucyu-shi	Tokyo	Japan	183-8561
40	National Center for Child Health and Development /ID# 251926	Setagaya-ku	Tokyo	Japan	157-8535
41	Kyungpook National University Chilgok Hospital /ID# 252663	Daegu		Korea, Republic of	41404
42	Seoul National University Hospital /ID# 252024	Seoul		Korea, Republic of	03080
43	Samsung Medical Center /ID# 252023	Seoul		Korea, Republic of	06351
44	Panamerican Clinical Research Mexico S.A de C.V /ID# 252229	Cuernavaca	Morelos	Mexico	62290
45	Servicios de Oncologia Medica Integral SA de CV /ID# 252974	San Pedro Garza Garcia	Nuevo Leon	Mexico	66220
46	Academisch Medisch Centrum /ID# 250845	Amsterdam		Netherlands	1105 AZ
47	Universitair Medisch Centrum Groningen /ID# 252003	Groningen		Netherlands	9713 GZ
48	Gastromed /Id# 251290	Torun	Kujawsko-pomorskie	Poland	87-100
49	Uniwersytecki Szpital Dzieciecy w Krakowie /ID# 251387	Krakow	Malopolskie	Poland	30-663
50	Instytut Pomnik - Centrum Zdrowia Dziecka /ID# 251289	Warszawa	Mazowieckie	Poland	04-730
51	Hospital Arquitecto Marcide - Complejo Hospitalario Universitario de Ferrol /ID# 252105	Ferrol	A Coruna	Spain	15405
52	Hospital Sant Joan de Deu /ID# 251194	Esplugues de Llobregat	Barcelona	Spain	08950
53	Hospital Universitario Vall d'Hebron /ID# 252104	Barcelona		Spain	08035
54	National Taiwan University Hospital /ID# 251650	Taipei City		Taiwan	100
55	Linkou Chang Gung Memorial Hospital /ID# 251654	Taoyuan City		Taiwan	333
56	Gazi University Medical Faculty /ID# 251768	Ankara		Turkey	06560
57	Ankara Universitesi Fakultesi /ID# 252487	Ankara		Turkey	06620
58	Istanbul University-Cerrahpasa, Cerrahpasa Medical Faculty /ID# 252002	Istanbul		Turkey	34098
59	University Hospital Southampton NHS Foundation Trust /ID# 252097	Southampton	Hampshire	United Kingdom	SO16 6YD
60	Barts Health NHS Trust /ID# 251917	London	London, City Of	United Kingdom	E1 2ES
61	Great Ormond Street Hospital for Children /ID# 252126	London	London, City Of	United Kingdom	WC1N 3JH
62	Birmingham Women's and Children's NHS Foundation Trust /ID# 253072	Birmingham		United Kingdom	B4 6NH
63	Sheffield Children's Hospital /ID# 251600	Sheffield		United Kingdom	S10 2TH