A Study of the Efficacy and Safety of Upadacitinib (ABT-494) in subjects with Moderately to Severely Active Ulcerative Colitis

• Register: EUCTR
• Last refreshed on: 21 July 2021
• Main ID: EUCTR2016-000642-62-DE
• Date of registration: 18/10/2018
• Prospective Registration: Yes
• Primary sponsor: AbbVie Deutschland GmbH & Co. KG
• Public title: A Study of the Efficacy and Safety of Upadacitinib (ABT-494) in subjects with Moderately to Severely Active Ulcerative Colitis
• Scientific title: M14-675, A Multicenter, Randomized, Double-Blind, Placebo-Controlled Induction Study to Evaluate the Efficacy and Safety of Upadacitinib (ABT-494) in Subjects with Moderately to Severely Active Ulcerative Colitis
• Date of first enrolment: 04/11/2019
• Target sample size: 522
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2016-000642-62
• 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: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Argentina, Australia, Austria, Belarus, Bosnia and Herzegovina, Brazil, Canada, Chile, China, Colombia, Croatia, Czech Republic, Finland, France, Germany, Greece, Hungary, Ireland, Israel, Italy, Japan, Korea, Republic of, Latvia, Lithuania, Malaysia, Mexico, Netherlands, Norway, Poland, Portugal, Puerto Rico, Russian Federation, Serbia, Singapore, Slovakia, South Africa, Spain, Sweden, Switzerland, Taiwan, Turkey, 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: 9
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 464
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 49

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: 45-
Pharmaceutical form of the placebo: Tablet
Route of administration of the placebo: Oral use

Primary Outcome(s)

Primary end point(s): The primary endpoint for Study M14-675 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 sub score = 1) at Week 8.

Main Objective: The objective of Study M14-675 (Phase 3 induction) is to evaluate the efficacy and safety of upadacitinib 45 mg once daily (QD) compared to placebo in inducing clinical remission (per Adapted Mayo score) in subjects with moderately to severely active ulcerative colitis.

Secondary Objective: The secondary objectives of the study are to evaluate the efficacy of upadacitinib 45 mg QD comparing with placebo in ranked secondary endpoints of achieving endoscopic improvement, endoscopic remission, clinical response per Adapted Mayo Score, clinical response per Partial Adapted Mayo score, histologic-endoscopic mucosal improvement, no bowel urgency, no abdominal pain, histologic mprovement, mucosal healing, and change in IBDQ total core and FACIT-F score.

Timepoint(s) of evaluation of this end point: Part 1: Week 8 and Part 2: Week 16 (Extended Treatment Period; as applicable)

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: For points 1,2,3,5,6,7,8,9,10,11 - week 8
For point 4 - Week 2

Secondary end point(s): 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 muscosal
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

Secondary ID(s)

2016-000642-62-NL

M14-675

Source(s) of Monetary Support

AbbVie Inc

Ethics review

Status: Approved
Approval date: 04/11/2019
Contact: