A study of the Efficacy and Safety of Upadacitinib (ABT-494) in Subjects with Moderately to Severely Active Crohn's Disease Who Have Inadequately Responded to or are Intolerant to Biologic Therapy

• Register: EUCTR
• Last refreshed on: 26 October 2021
• Main ID: EUCTR2017-001226-18-HU
• Date of registration: 07/03/2018
• 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 Crohn's Disease Who Have Inadequately Responded to or are Intolerant to Biologic Therapy
• Scientific title: A Multicenter, Randomized, Double-Blind, Placebo-Controlled Induction Study of the Efficacy and Safety of Upadacitinib (ABT-494) in Subjects with Moderately to Severely Active Crohn's Disease Who Have Inadequately Responded to or are Intolerant to Biologic Therapy
• Date of first enrolment: 18/05/2018
• Target sample size: 645
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2017-001226-18
• 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: yes; Other trial design description: Part 1 Randomized, double-blind 2arm Part 2 Open Label 1arm Part 3 Extension Treatment Period 3arm; 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, Belgium, Bosnia and Herzegovina, Brazil, Bulgaria, Canada, Chile, China, Colombia, Croatia, Czech Republic, Denmark, Egypt, Estonia, Germany, Hong Kong, Hungary, Ireland, Israel, Italy, Japan, Korea, Republic of, Latvia, Lithuania, Malaysia, Mexico, Poland, Portugal, Puerto Rico, Russian Federation, Serbia, Singapore, Slovakia, Slovenia, 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:
- Confirmed diagnosis of CD for at least 3 months prior to Baseline.
- Confirmed diagnosis of moderate to severe CD as assessed by stool frequency (SF), abdominal pain (AP) score.
- Evidence of mucosal inflammation based on the Simplified Endoscopic Score for Crohn's disease (SES-CD) on an endoscopy confirmed by a central reader.
- Demonstrated an inadequate response or intolerance to any biologic therapy for infliximab, adalimumab, certolizumab pegol, vedolizumab, and ustekinumab.
- If female, subject must meet the contraception recommendations
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 613
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 32

Exclusion criteria:
Subject with a current diagnosis of ulcerative colitis or indeterminate colitis.
- Subject not on stable doses of CD related antibiotics, oral aminosalicylates, corticosteroids or methotrexate (MTX).
- Subject with the following known complications of CD: abscess (abdominal or peri-anal), symptomatic bowel strictures, > 2 missing segments of the following 5 segments: terminal ileum, right colon, transverse colon, sigmoid and left colon, and rectum; fulminant colitis, toxic megacolon, or any other manifestation that might require surgery while enrolled in the study.
- Subject with ostomy or ileoanal pouch
- Subject diagnosed with short gut or short bowel syndrome
- Screening laboratory and other analyses show abnormal results.


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

Health Condition(s) or Problem(s) studied

Crohn's Disease (CD)
MedDRA version: 20.0 Level: PT Classification code 10011401 Term: Crohn's disease System Organ Class: 10017947 - Gastrointestinal disorders

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

Intervention(s)

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

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

Primary Outcome(s)

Secondary Objective: To evaluate improvements in several efficacy parameters, including steroid discontinuation, laboratory parameters and quality of life questionnaires.

Primary end point(s): Co-primary Endpoints:
1. Proportion of subjects with clinical remission per PROs at Week 12
2. Proportion of subjects with endoscopic response at Week 12

Main Objective: The objective of this study is to evaluate the efficacy and safety of upadacitinib compared to placebo as induction therapy in subjects with moderately and severely active Crohn's disease (CD).

Timepoint(s) of evaluation of this end point: Week 12
Week 12

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: 1. week 12
2. week 4
3. week 12
4. week 12
5. week 12
6. week 12
7. week 2
8. week 12
9. week 12
10. week 12

Secondary end point(s): 1. Proportion of subjects with clinical remission per CDAI (CDAI < 150)
2. Proportion of subjects with clinical remission at Week 4
3. Proportion of subjects with endoscopic remission at Week 12
4. Proportion of subjects who discontinue corticosteroid use for CD and achieve clinical remission at Week 12, in subjects taking corticosteroids for CD at Baseline
5. Change from Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue at Week 12
6. Change from Baseline in Inflammatory Bowel Disease Questionnaire (IBDQ) at Week 12
7. Proportion of subjects achieving CR-100 at Week 2
8. Proportion of subjects achieving CR-100 at Week 12
9. Proportion of subjects with hospitalizations due to CD at during the 12 week double-blind induction period
10. Proportion of subjects with resolution of extra-intestinal manifestation (EIM) at Week 12, in subjects with EIM at Baseline

Secondary ID(s)

M14-431

2017-001226-18-SK

Source(s) of Monetary Support

AbbVie Inc.

Ethics review

Status: Approved
Approval date: 10/05/2018
Contact: