A Maintenance and Long-Term Extension Study of the Efficacy and Safety of Upadacitinib (ABT-494) in Subjects with Crohn's Disease who Completed the Studies M14-431 or M14-433

• Register: EUCTR
• Last refreshed on: 27 July 2020
• Main ID: EUCTR2017-001225-41-HU
• Date of registration: 07/03/2018
• Prospective Registration: Yes
• Primary sponsor: AbbVie Deutschland GmbH & Co. KG
• Public title: A Maintenance and Long-Term Extension Study of the Efficacy and Safety of Upadacitinib (ABT-494) in Subjects with Crohn's Disease who Completed the Studies M14-431 or M14-433
• Scientific title: A Multicenter, Randomized, Double-Blind, Placebo- Controlled Maintenance and Long-Term Extension Study of the Efficacy and Safety of Upadacitinib (ABT-494) in Subjects with Crohn's Disease who Completed the Studies M14-431 or M14-433
• Date of first enrolment: 18/05/2018
• Target sample size: 747
• Recruitment status: Authorised-recruitment may be ongoing or finished
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2017-001225-41
• 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: Substudy 1 Randomized, double-blind. Substudy 2 Both open-label and double-blind; If controlled, specify comparator, Other Medicinial Product: no; Placebo: yes; Other: no; Number of treatment arms in the trial: 3
• 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, Germany, Hong Kong, Hungary, Ireland, Israel, Japan, Korea, Republic of, Latvia, Lithuania, Malaysia, Mexico, Netherlands, 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:
For Substudy 1:
- Subject who receive double-blind treatment in Study M14- 431 or Study M14-433 and achieve clinical response.
- Subject completes Week 12 study procedures in study M14-431 or study M14-433. The final endoscopy for studies M14-431 or M14-433 may be missing, if the endoscopy cannot be performed during the coronavirus SARS-CoV-2 pandemic.
For Substudy 2:
- Subject completes Substudy 1 of Study M14-430. The week 52 endoscopy may be missing, if the endoscopy cannot be performed during the coronavirus SARS-CoV-2 pandemic.
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 710
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 37

Exclusion criteria:
For Sub-studies 1 and 2:
- Subject is considered by the investigator, for any reason, to be an unsuitable candidate for the study.
- Subject who has a known hypersensitivity to upadacitinib or its excipients, or had an adverse event during Study M14-431, M14-433,or Substudy 1 of Study M14-430 that in the investigator's judgment makes the subject unsuitable for this study.
- Subject with any active or chronic recurring infections based on the investigator's assessment that makes the subject an unsuitable candidate for the study. Subjects with serious infections undergoing treatment may be enrolled BUT NOT dosed until the infection treatment has been completed and the infection is resolved, based on the investigator's assessment.
- Subject with high grade colonic dysplasia or malignancy diagnosed at the endoscopy performed at the final visit of Study M14-431, M14-433,or Substudy 1 of Study M14-430 (Week 52).


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

Health Condition(s) or Problem(s) studied

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

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

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: 30-
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: 15-
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use

Primary Outcome(s)

Main Objective: Substudy 1 (randomized, double-blind, placebo-controlled maintenance): To evaluate the efficacy and safety of two doses of upadacitinib versus placebo as maintenance therapy in subjects with moderately to severely active Crohn's disease (CD) who responded to upadacitinib induction treatment in Studies M14-431 or M14-433.
Substudy 2 (long-term extension [LTE]): To evaluate safety and efficacy of long-term administration of upadacitinib in subjects with moderately to severely active CD who participated in the Phase 3 upadacitinib induction and maintenance studies.

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

Primary end point(s): Substudy 1, Cohort 1 (Upadacitinib vs Placebo)
Co-Primary Endpoints:
? Proportion of subjects with clinical remission per PROs at Week 52, AND
? Proportion of subjects with endoscopic response at Week 52

Substudy 2
Primary Endpoint: Incidence of AEs over time

Timepoint(s) of evaluation of this end point: Week 52

Secondary Outcome(s)

Secondary end point(s): Substudy 1
1. Proportion of subjects with clinical remission per CDAI (CDAI < 150) at Week 52
2. Proportion of subjects with clinical remission at Week 0 and Week 52
3. Proportion of subjects with endoscopic remission at Week 52
4. Change in Baseline in Inflammatory Bowel Disease Questionnaire (IBDQ) at Week 52
5. Proportion of subjects achieving CR-100 at Week 52
6. Change from Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) at Week 52
7. Proportion of subjects with clinical remission and endoscopic remission at Week 52
8. Proportion of subjects who discontinue corticosteroid use for CD at 90 days and achieve clinical remission per PROs at Week 52 in subjects taking corticosteroids for CD at Baseline of induction
9. Proportion of subjects with CD-related hospitalizations during the 52-Week double-blind maintenance period.
10. Proportion of subjects with resolution of extra-intestinal manifestation (EIM) at Week 52, in subjects with EIMs at Baseline.

Substudy 2
Proportion of subjects
? with clinical remission per PROs over time
? with enhanced clinical response per PROs over time
? with clinical response per PROs over time
? with clinical remission per CDAI (CDAI<150) over time
? with CR-100 over time
? with endoscopic remission at Week 0, and every 48 weeks thereafter
? with endoscopic response at Week 0, and every 48 weeks thereafter
? who discontinue corticosteroid use and achieve clinical remission per PROs over time among subjects taking steroids at Baseline (of induction)

Time loss of
? enhanced clinical response
? clinical remission

Timepoint(s) of evaluation of this end point: Substudy 1
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

Substudy 2
Over study duration

Secondary ID(s)

2017-001225-41-SK

M14-430

Source(s) of Monetary Support

AbbVie Inc.

Ethics review

Status: Approved
Approval date: 11/05/2018
Contact: