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

Overview

Sponsor-declared trial summary

Key facts

Sponsor

AbbVie Deutschland GmbH & Co. KG

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Digestive System Diseases [C06]

Trial duration

27 Jul 2017 → ongoing

Decision date (initial)

2023-10-30

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

AbbVie Inc.

External identifiers

EU CT number

2023-504951-29-00

EudraCT number

2017-001225-41

ClinicalTrials.gov

NCT03345823

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacodynamic, Pharmacokinetic, Therapy, Efficacy, Safety

Sub-study 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.

Sub-study 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 objectives 1

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

Conditions and MedDRA coding

Chron's Disease

Study design 2 periods

Regulatory references

Scientific advice from competent authorities

European Medicines Agency

Plan to share IPD

Yes

IPD plan description

AbbVie is committed to responsible clinical trial data sharing. This includes access to anonymized, individual and trial-level data (analysis data sets), as well as other information. To learn more about the process, or to submit a request, visit the following link https://www.abbvieclinicaltrials.com/hcp/data-sharing/ For details on when studies are available for sharing visit https://vivli.org/ourmember/abbvie/

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 4

1. Sub-study 1: Subject who receive double-blind treatment in Study M14- 431 or Study M14-433 and achieve clinical response.
2. Sub-study 1: Subject completes Week 12 or Week 24 study procedures in study M14431 or study M14-433. The final endoscopy for studies M14-431 or M14433 may be missing, if the endoscopy cannot be performed during the coronavirus SARS-CoV-2 pandemic.
3. Sub-study 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.
4. Sub-study 2: Subject achieved clinical response at Week 24 and completed Week 24 visit and procedures in Part 3/Cohort 3 of Study M14-431.

Exclusion criteria 5

1. Sub-study 1 and 2: Subject is considered by the investigator, for any reason, to be an unsuitable candidate for the study
2. Sub-study 1 and 2: Subject who has a known hypersensitivity to upadacitinib or its excipients, or had an AE during Studies M14-431, M14-433, or Sub-study 1 or 2 of Study M14-430 that, in the investigator's judgment, makes the subject unsuitable for this study
3. Sub-study 1 and 2: 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
4. Sub-study 1 and 2: 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
5. Sub-study 1 and 2: Subjects with high grade colonic dysplasia or malignancy diagnosed at the endoscopy performed at the final visit of Studies M14-431, M14-433, or Sub-study 1 or 2 of Study M14-430

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 3

1. Sub-study 1 Cohort 1 (Upadacitinib vs Placebo): Proportion of subjects with clinical remission per PROs at Week 52
2. Sub-study 1 Cohort 1 (Upadacitinib vs Placebo): Proportion of subjects with endoscopic response at Week 52
3. Sub-study 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

Secondary endpoints 20

1. Sub-study 1: Proportion of subjects with clinical remission per CDAI at Week 52
2. Sub-study 1: Proportion of subjects with endoscopic remission at Week 52
3. Sub-study 1: Change from Baseline in IBDQ at Week 52
4. Sub-study 1: Proportion of subjects achieving CR-100 at Week 52
5. Sub-study 1: 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. Sub-study 1: 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. Sub-study 1: Proportion of subjects with clinical remission per PROs at Week 0 and Week 52
8. Sub-study 1: Change from Baseline in FACIT-F at Week 52
9. Sub-study 1: Proportion of subjects with clinical remission per PROs and endoscopic remission at Week 52
10. Sub-study 1: Proportion of subjects with CD-related hospitalizations during the 52 Week double-blind maintenance period
11. Sub-study 1: Proportion of subjects with resolution of EIMs at Week 52, in subjects with EIMs at Baseline
12. Sub-study 2: Proportion of subjects with clinical remission over time
13. Sub-study 2: Proportion of subjects with enhanced clinical response over time
14. Sub-study 2: Proportion of subjects with clinical response over time
15. Sub-study 2: Proportion of subjects with CR-100 over time
16. Sub-study 2: Proportion of subjects with endoscopic remission at Week 0, and every 48 weeks thereafter
17. Sub-study 2: Proportion of subjects with endoscopic response at Week 0, and every 48 weeks thereafter
18. Sub-study 2: Proportion of subjects without corticosteroid use for CD and achieve clinical remission over time
19. Sub-study 2: Time loss of enhanced clinical response
20. Sub-study 2: Time loss of clinical remission

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

AbbVie Deutschland GmbH & Co. KG

Sponsor organisation

AbbVie Deutschland GmbH & Co. KG

Address

Knollstrasse

City

Ludwigshafen Am Rhein

Postcode

67061

Country

Germany

Scientific contact point

Organisation

AbbVie Deutschland GmbH & Co. KG

Contact name

Global Clinical Trials Helpdesk

Public contact point

Organisation

AbbVie Deutschland GmbH & Co. KG

Contact name

Global Clinical Trials Helpdesk

Third parties 7

Locations

19 EU/EEA countries · 71 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 153 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

8 submissions — initial application plus substantial / non-substantial modifications