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

• Register: EUCTR
• Last refreshed on: 31 August 2020
• Main ID: EUCTR2016-000641-31-GB
• Date of registration: 11/01/2017
• Prospective Registration: No
• 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: 07/12/2016
• Target sample size: 1055
• Recruitment status: Authorised-recruitment may be ongoing or finished
• 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)

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.

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

Primary end point(s): The primary endpoint for Phase 2b Induction (Substudy 1) is the proportion of subjects who achieve clinical remission per Adapted Mayo score (defined as SFS = 1, RBS of 0, and endoscopic subscore = 1) at Week 8.

The primary endpoint for Phase 3 Induction (Substudy 2) is the proportion of subjects who achieve clinical remission per Adapted Mayo score (defined as SFS = 1 and not greater than Baseline, RBS of 0, and endoscopic subscore = 1) at Week 8. Note in Substudy 2, evidence of friability during endoscopy in subjects with otherwise "mild" endoscopic activity will confer an endoscopic subscore of 2.

The primary endpoint for Phase 3 maintenance (Substudy 3) is the proportion of subjects who achieve clinical remission per Adapted Mayo score (definition same as definition in Substudy 2) at Week 52.

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: Substudy 1:
1. Week 8
2. Week 8
3. Week 8
4. Week 2
5. Week 8
6. Week 8
7. Week 8

Substudy 2:
1. Week 8
2. Week 8
3. Week 8
4. Week 2
5. Week 8
6. Week 8
7. Week 8
8. Week 8
9. Week 8
10. Week 8
11. Week 8

Substudy 3:
1. Week 52
2. Week 52
3. Week 52
4. Week 52
5. Week 52
6. Week 52
7. Week 52
8. Week 52
9. Week 52
10. Week 52
11. Week 52
12. Week 52
13. Week 52
14. Week 52

Secondary end point(s): Substudy 1:
1. Proportion of subjects with endoscopic improvement (defined as an endoscopic subscore = 1) at Week 8

2. Proportion of subjects achieving clinical remission per Full Mayo score (defined as a Full Mayo score = 2 with no subscore > 1) at Week 8

3. Proportion of subjects achieving clinical response per Adapted Mayo score (defined as decrease from baseline in the Adapted Mayo score = 2 points and = 30% from baseline, PLUS a decrease in rectal bleeding subscore (RBS) = 1 or an absolute RBS = 1) at Week 8

4. Proportion of subjects achieving clinical response per Partial Mayo score (using the Mayo Scoring System for Assessment of Ulcerative Colitis Activity, excluding endoscopic subscore; clinical response defined as decrease from baseline in the Partial Mayo score = 2 points and = 30% from baseline, PLUS a decrease in rectal bleeding subscore (RBS) = 1 or an absolute RBS = 1) at Week 2

5. Change in Full Mayo score from Baseline to Week 8

6. Proportion of subjects with endoscopic remission (defined as an endoscopic subscore of 0) at Week 8

7. Proportion of subjects who achieved histologic improvement (defined as decrease from baseline in Geboes score) at Week 8

Substudy 2:
1. Proportion of subjects with endoscopic improvement at Week 8

2. Proportion of subjects with endoscopic remission at Week 8

3. Proportion of subjects achieving clinical response per Adapted Mayo Score at Week 8

4. Proportion of subjects achieving clinical response per Partial Adapted Mayo score (defined as decrease from Baseline = 1 points and = 30% from Baseline, PLUS a decrease in RBS = 1 or an absolute RBS = 1) at Week 2

5. Proportion of subjects achieving histologic-endoscopic mucosal improvement at Week 8

6. Proportion of subjects who reported no bowel urgency at Week 8

7. Proportion of subjects who reported no abdominal pain at Week 8

8. Proportion of subjects who achieved histologic improvement at Week 8

9. Change from Baseline in IBDQ total score at Week 8

10. Proportion of subjects with mucosal healing at Week 8

11. Change from Baseline in FACIT-F score at Week 8

Substudy 3:
1. Proportion of subjects with endoscopic improvement

2. Proportion of subjects who maintain clinical remission per Adapted Mayo score among subjects who achieved clinical remission per Adapted Mayo score in Study M14-234 (Substudy 1 or 2) or Study M14-675

3. Proportion of subjects who achieved clinical remission at Week 52 per adapted Mayo score and were corticosteroid free for = 90 days among subjects in clinical remission in the end of the induction treatment in Study M14-234 (Substudy 1 or 2) or Study M14-675.

4. Proportion of subjects with endoscopic improvement among subjects with endoscopic improvement in Study M14-234 (Substudy 1 or 2) or Study M14-675

5. Proportion of subjects with endoscopic remission

6. Proportion of subjects maintain clinical response per Adapted Mayo score

7. Proportion of subjects with histologic-endoscopic mucosal improvement

8. Change from Baseline in IBDQ total score

9. Proportion of subjects with mucosal healing

10. Proportion of subjects who reported no bowel urgency

11. Proportion of subjects who reported no abdominal pain

12. Change from Baseline in FACIT-F score

13. Incidence rate of UC-related hospitalizations

14. Incidence rate of UC-related surgeries

Secondary ID(s)

2016-000641-31-SK

M14-234

Source(s) of Monetary Support

AbbVie Inc.

Ethics review

Status: Approved
Approval date: 07/12/2016
Contact: