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 Conventional and/or Biologic Therapies

• Register: EUCTR
• Last refreshed on: 2 March 2022
• Main ID: EUCTR2017-001240-35-AT
• Date of registration: 28/02/2018
• 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 Conventional and/or Biologic Therapies
• 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 Conventional and/or Biologic Therapies
• Date of first enrolment: 12/03/2018
• Target sample size: 501
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2017-001240-35
• 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, Belgium, Bosnia and Herzegovina, Brazil, Bulgaria, Canada, Chile, China, Colombia, Croatia, Denmark, Egypt, Estonia, France, Germany, Hong Kong, Hungary, Ireland, Israel, Italy, Japan, Korea, Republic of, Latvia, Lithuania, Malaysia, Mexico, Netherlands, 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 one or more conventional and/or biologic therapies, in the opinion of the investigator, as defined below:
Oral locally acting steroids
Intravenous or oral corticosteroids
Immunosuppressants
Biologic therapies for CD
Note: Non-bio-IR subjects who have received prior biologic for up to 1 year but have not failed may be enrolled; however, participants must have discontinued the biologic for reasons other than inadequate response or intolerance (e.g., change of insurance, well controlled disease),
- 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 476
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 25

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), > 2 entire missing segments of the following 5 segments: terminal ileum, right colon, transverse
colon, sigmoid and left colon, and rectum, symptomatic bowel strictures, 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)

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

Primary end point(s): Co-primary Endpoints:
1. Proportion of subjects with clinical remission at per PROs Week 12, and
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 participants with moderately and severely active Crohn's disease (CD).

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

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
10. week 12

Secondary end point(s): 1. Proportion of subjects with clinical remission per CDAI (CDAI < 150) in subjects with a Baseline CDAI of 220 to 450 at Week 12
2. Proportion of subjects with clinical remission at Week 4
3. Proportion of subjects with enhanced clinical response at Week 2
4. Proportion of subjects with endoscopic remission at Week 12
5. Proportion of subjects who discontinue corticosteroid use for CD and achieve clinical remission at Week 12, in subjects taking corticosteroids for CD at Baseline
6. Change from Baseline in 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 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)

M14-433

2017-001240-35-SK

Source(s) of Monetary Support

AbbVie Inc.

Ethics review

Status: Approved
Approval date: 13/02/2018
Contact: