Efficacy and Safety of Upadacitinib (ABT-494) in Subjects With Moderately to Severely Active Ulcerative Colitis

• Register: EUCTR
• Last refreshed on: 24 January 2022
• Main ID: EUCTR2016-000641-31-AT
• Date of registration: 11/10/2016
• Prospective Registration: Yes
• Primary sponsor: AbbVie Deutschland GmbH & Co. KG
• Public title: Efficacy and Safety of Upadacitinib (ABT-494) in Subjects With Moderately to Severely Active Ulcerative Colitis
• Scientific title: A Multicenter, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Safety and Efficacy of Upadacitinib (ABT-494) for Induction and Maintenance Therapy in Subjects with Moderately to Severely Active Ulcerative Colitis
• Date of first enrolment: 17/10/2016
• Target sample size: 1055
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2016-000641-31
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: no; Single blind: no; Double blind: yes; Parallel group: no; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: no; Placebo: yes; Other: no; Number of treatment arms in the trial: 5
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Argentina, Australia, Austria, Belarus, Belgium, Bosnia and Herzegovina, Brazil, Canada, Chile, China, Colombia, Croatia, Czech Republic, Egypt, Estonia, European Union, Finland, France, Germany, Greece, Hungary, Ireland, Israel, Japan, Kazakhstan, Korea, Republic of, Latvia, Lithuania, Malaysia, Mexico, Netherlands, New Zealand, Norway, Poland, Portugal, Puerto Rico, Russian Federation, Saudi Arabia, Serbia, Singapore, Slovakia, South Africa, Spain, Sweden, Switzerland, Taiwan, Ukraine, United Kingdom, United States

Contacts

• Name: EU Clinical Trials Helpdesk
• Affiliation: AbbVie Ltd

• Name: EU Clinical Trials Helpdesk
• Affiliation: AbbVie Ltd

Key inclusion & exclusion criteria

Inclusion criteria:
1. Male or female between 16 and 75 years of age at Baseline.
- Adolescent subjects at the age of 16 and 17 years old will be enrolled if approved by the country or regulatory/health authority. If these approvals have not been granted, only subjects = 18 years old will be enrolled.
- Adolescent subjects at the age of 16 and 17 years old must weigh = 40 kg and meet the definition of Tanner Stage 5 (refer to Appendix J) at the screening Visit.
2. Diagnosis of ulcerative colitis for 90 days or greater prior to Baseline, confirmed by colonoscopy
3. Moderately to severely active ulcerative colitis
4. Demonstrated an inadequate response to, loss of response to, or intolerance to immunosuppressants, corticosteroids or biologic therapies
5. Negative pregnancy test for female subjects of childbearing potential
Are the trial subjects under 18? yes
Number of subjects for this age range: 21
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 981
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 53

Exclusion criteria:
1. Subject with current diagnosis of Crohn's disease (CD) or diagnosis of indeterminate colitis (IC).
2. Current diagnosis of fulminant colitis and/or toxic megacolon.
3. Subject with disease limited to the rectum (ulcerative proctitis) during the screening endoscopy.
4. Received cyclosporine, tacrolimus, mycophenolate mofetil, or thalidomide within 30 days prior to Baseline.
5. Subject who received azathioprine or 6-mercaptopurine within 10 days of Baseline.
6. Received intravenous corticosteroids within 14 days prior to Screening or during the Screening Period.
7. Subject with previous exposure to JAK inhibitor.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Digestive System Diseases [C06]

Ulcerative Colitis
MedDRA version: 20.0 Level: PT Classification code 10009900 Term: Colitis ulcerative System Organ Class: 10017947 - Gastrointestinal disorders

Intervention(s)

Product Name: Upadacitinib
Product Code: ABT-494
Pharmaceutical Form: Tablet
INN or Proposed INN: Upadacitinib
CAS Number: 1310726-60-3
Current Sponsor code: ABT-494
Other descriptive name: ABT-494
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 7.5-
Pharmaceutical form of the placebo: Tablet
Route of administration of the placebo: Oral use

Product Name: Upadacitinib
Product Code: ABT-494
Pharmaceutical Form: Tablet
INN or Proposed INN: Upadacitinib
CAS Number: 1310726-60-3
Current Sponsor code: ABT-494
Other descriptive name: ABT-494
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 15-
Pharmaceutical form of the placebo: Tablet
Route of administration of the placebo: Oral use

Product Name: Upadacitinib
Product Code: ABT-494
Pharmaceutical Form: Tablet
INN or Proposed INN: Upadacitinib
CAS Number: 1310726-60-3
Current Sponsor code: ABT-494
Other descriptive name: ABT-494
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 30-
Pharmaceutical form of the placebo: Tablet
Route of administration of the placebo: Oral use

Product Name: Upadacitinib
Product Code: ABT-494
Pharmaceutical Form: Tablet
INN or Proposed INN: Upadacitinib
CAS Number: 1310726-60-3
Current Sponsor code: ABT-494
Other descriptive name: ABT-494
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 45-
Pharmaceutical form of the placebo: Tablet
Route of administration of the placebo: Oral use

Primary Outcome(s)

Timepoint(s) of evaluation of this end point: Substudy 1 and 2: Week 8., 16
Substudy 3: Week 44, 52.

Primary end point(s): Substudy 1 and 2: The proportion of subjects who achieve clinical remission per Adapted Mayo score at Week 8 or week 16.
Substudy 3: The proportion of subjects who achieve clinical remission per Adapted Mayo score at Week 44 or 52.

Main Objective: Main objective of SS1 (Ph2b induction) is to characterize dose-response, efficacy, and safety of upadacitinib compared to placebo in inducing clinical remission defined by Adapted Mayo score in subjects with moderately to severely active ulcerative colitis (UC) in order to identify the induction dose of upadacitinib for further evaluation in Phase 3 studies, SS1 has closed enrollment and all subjects have completed the induction phase.
Main objective of SS2 (Ph3 induction) is to evaluate efficacy and safety of upadacitinib 45 mg once daily (QD) compared to placebo in inducing clinical remission in subjects with moderately to severely active UC.
Main objective of SS3 (Ph3 maintenance) is to evaluate efficacy and safety of upadacitinib 15 mg QD and 30 mg QD compared to placebo in achieving clinical remission in subjects with moderately to severely active UC who achieved clinical response following induction with upadacitinib in M14-234 SS1 or 2 or M14-675.

Secondary Objective: evaluate the efficacy of upadacitinib as an induction and maintenance therapy in ranked 2nd endpoints

Secondary Outcome(s)

Secondary end point(s): Substudy 1 and 2:
1. Proportion of subjects with endoscopic subscore = 1 at Week 8 or 16
2. Proportion of subjects achieving clinical remission per Full Mayo score at Week 8 or 16
3. Proportion of subjects achieving clinical response per Adapted Mayo score at Week 8 or 16

Substudy 3:
1. Proportion of subjects with endoscopic improvement at Week 44 or 52
2. Proportion of subjects achieving clinical remission per Full Mayo score at Week 44 or 52
3. Proportion of subjects who discontinued corticosteroid use and achieved clinical remission per Adapted Mayo score at Week 44 or 52

Timepoint(s) of evaluation of this end point: Substudy 1 and 2: Week 8 and 16.
Substudy 3: Week 44 and 52.

Secondary ID(s)

M14-234

2016-000641-31-SK

Source(s) of Monetary Support

AbbVie Inc.

Ethics review

Status: Approved
Approval date: 27/07/2016
Contact: