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

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

Status

Active, not recruiting

Phases

Phase 3

Study type

Interventional

Source

EU CTR

Registry ID

EUCTR2017-001225-41-SE

Enrollment

906

Registered

2018-02-12

Start date

2018-03-15

Completion date

Unknown

Last updated

2024-02-26

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

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

Interventions

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:

Eligibility

Sex/Gender

All

Inclusion 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 =65 years) yes F.1.3.1 Number of subjects for this age range 28

Exclusion criteria

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 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.

Design outcomes

Primary

Measure	Time frame
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.;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 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. ;Timepoint(s) of evaluation of this end point: Week 52	—

Measure

Time frame

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

—

Secondary

Measure	Time frame
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	—

Measure

Time frame

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

—

Countries

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

Public ContactGlobal Clinical Trials Helpdesk

AbbVie Ltd

global-clinical-trials@abbvie.com441628561090

Outcome results

None listed

Source: EU CTR (via WHO ICTRP) · Data processed: Feb 4, 2026