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: 8 April 2024
• Main ID: EUCTR2017-001225-41-AT
• Date of registration: 07/02/2018
• 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: 19/02/2018
• Target sample size: 906
• Recruitment status: Not Recruiting
• 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 and 2 Randomized Double Blind Open Label Substudy 3 Dose Optimization 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, France, Germany, Hong Kong, Hungary, Ireland, Israel, Italy, Japan, Korea, Republic of, Latvia, Lithuania, Malaysia, Mexico, Netherlands, Portugal, Puerto Rico, Romania, Russian Federation, Serbia, Singapore, Slovakia, Slovenia, South Africa, Spain, Sweden, Switzerland, Taiwan, Turkey, Ukraine, United Kingdom, United States

Contacts

• Name: Global Clinical Trials Helpdesk
• Affiliation: AbbVie Ltd

• Name: Global 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 or Week 24 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.
- Subject achieved clinical response at Week 24 and completed Week 24 visit and procedures in Part 3/Cohort 3 of Study M14-431.

For Substudy 3
-Subject is an ongoing subject in Substudy 2 for at least 12 months
-Subject has received open-label upadacitinib 30 mg QD for at least 6
months during Substudy 2
-Subject is in stable remission for at least 6 months defined as:
a.CDAI < 150 AND
b.CRP < 5 mg/L and FCP < 250 mg/kg AND
c.Subject has not been on locally acting (rectal or suppository) or
systemic corticosteroids for CD = 90 days prior to the entry of Substudy 3.

NOTE: Hematocrit for baseline CDAI calculation, CRP, and FCP should be assessed within 4 weeks prior to enrolment to confirm subjects are in stable remission at time of enrolment into the substudy and will serve as Baseline (Week 0) results.
-In the past 3 months the subject has not received any new medication or increase of the dose of current concomitant medication for treatment of CD



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 878
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 28

Exclusion criteria:
Substudy 1, 2 and 3
-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 AE during Studies M14-431, M14-433, or Substudy 1 or 2 of Study M14-430 that, in the investigator's judgment, makes the subject unsuitable for this study.
-Subjects who anticipate the need for any live vaccine during study participation including at least 30 days (or longer, if required locally after the last dose of study drug.
-Female subjects with a confirmed positive pregnancy test at the final visit in Studies M14-431, M14-433, or Substudy 1 of Study M14-430, or who is considering becoming pregnant during the study.
-Subject is not in compliance with prior and concomitant medication requirements throughout Studies M14-431, M14-433, or Substudy 1 or 2 of Study M14-430 per investigator assessment.
-Subject at the final visit of M14-431 or M14-433 with any active or chronic recurring infections based on the investigator's assessment 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. -Current evidence of active or untreated latent tuberculosis. -Subjects with high grade colonic dysplasia or malignancy diagnosed at the endoscopy performed at the final visit of Studies M14-431, M14-433,
or Substudy 1 or 2 of Study M14-430.
-Current or history of malignancy or lymphoproliferative disease, including lymphoma, or signs and symptoms suggestive of possible lymphoproliferative disease, such as lymphadenopathy and/or splenomegaly; except for successfully treated non-metastatic cutaneous squamous cell, basal cell carcinoma, and/or localized carcinoma in situ of the cervix.
-Subject with a poorly controlled medical condition, such as uncontrolled diabetes, unstable ischemic heart disease, moderate or severe congestive heart failure, recent cerebrovascular accidents, and any other condition which, in the opinion of the investigator or sponsor, would put the subject at risk by participation in this study.
-Laboratory values from the visit immediately prior to the Substudy 1 Week 0 Visit or the Substudy 2 Week 0 Visit (for those subjects enrolling into Cohort 4) meeting the following criteria:
·EJAST or ALT > 3 x upper limit of normal (ULN)
·EJTotal WBC count < 2,000/pL
·EJAbsolute neutrophil count (ANC) < 1,000/pL
·EJPlatelet count < 50,000/pL
·EJAbsolute lymphocyte count < 500/pL
·EJHemoglobin <8 g/dL
-For Substudy 3 only: Total SES-CD >4 and/or subscore >1 in any segment in the Substudy 2 annual ileo-colonoscopy, if performed within 6 months prior to Week 0 in Substudy 3, based on the local
reader score.
-Enrollment in another interventional clinical study while participating in this study.



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: 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.

Substudy 3 (dose optimization): To evaluate the efficacy and safety of dose decrease of upadacitinib from 30 mg QD to 15 mg QD in subjects who are receiving open-label upadacitinib 30 mg QD and are in stable remission in Substudy 2.

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

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
Occurrence rate of subjects
with total hospitalizations (all-cause) over time
with CD-related hospitalizations over time
with surgeries over time
with CD-related surgeries over time

Substudy 3
Proportion of subjects with clinical remission per CDAI at Week 48 and without changes in CD-related medications and without corticosteroids during the 48-week period.

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: 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
11. week 52

Substudy 2
Over study duration

Substudy 3
48 weeks till study duration

Secondary end point(s): Substudy 1
1. Proportion of subjects with clinical remission per CDAI at Week 52
2. Proportion of subjects with endoscopic remission at Week 52
3. Change from Baseline in IBDQ at Week 52
4. Proportion of subjects achieving CR-100 at Week 52
5. Proportion of subjects without corticosteroid use for CD at least 90 days prior to Week 52 and achieved clinical remission per PROs at Week 52 (among all subjects)
6. Proportion of subjects who discontinued corticosteroid use for CD at least 90 days prior to Week 52 and achieved clinical remission per PROs at Week 52 in subjects taking corticosteroids for CD at Baseline of induction
7. Proportion of subjects with clinical remission per PROs at Week 0 and Week 52
8. Change from Baseline in FACIT-F at Week 52
9. Proportion of subjects with clinical remission per PROs and endoscopic remission at Week 52
10. .Proportion of subjects with CD-related hospitalizations during the 52 Week double-blind maintenance period.
11. Proportion of subjects with resolution of EIMs at Week 52, in subjects with EIMs at Baseline


Substudy 2
Proportion of subjects
? with clinical remission over time
? with enhanced clinical response over time
? with clinical response 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
? without corticosteroid use for CD and achieve clinical remission over time

Time loss of
? enhanced clinical response
? clinical remission

Substudy 3
1.Proportion of subjects who had Crohn's disease relapse at any time during the first 48 weeks in Substudy 3
2.Time from week 0 to Crohn's disease relapse
3.Proportion of subjects in clinical remission per CDAI at every scheduled visit
4.Proportion of subjects in clinical remission per PROs at every scheduled visit
5.Proportion of subjects with normal hsCRP (< 5 mg/L) at every scheduled visit
6.Proportion of subjects with normal FCP (< 250 mg/kg) at every scheduled visit
7.Proportion of subjects in clinical remission per CDAI and normal CRP at every scheduled visit
8.Proportion of subjects in clinical remission per CDAI and normal FCP
at every scheduled visit
Additional pre-specified endpoints are outlined in the protocol.

Secondary ID(s)

2017-001225-41-SK

M14-430

Source(s) of Monetary Support

AbbVie Inc.

Ethics review

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