This study has been transitioned to CTIS with ID 2023-504951-29-00 check the CTIS register for the current data. The objective of Substudy 1 (randomized, double-blind, placebo-controlled maintenance) is to evaluate the efficacy and safety of two…
ID
Source
Brief title
Condition
- Gastrointestinal inflammatory conditions
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Sub-study 1:
Proportion of subjects with clinical remission per PRO at Week 52, and
Proportion of subjects with endoscopic response at Week 52
Sub-study2:
Incidence of AEs over time
Secondary outcome
Sub-study 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 (as measured by the proportion of subjects with clinical remission at Week
52 among those with clinical remission at Week 0)
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 extra-intestinal manifestations
(EIMs) at Week 52, in subjects with EIMs at Baseline.
Sub-study 2: No Secondary Endpoints
Background summary
Crohn's disease (CD) encompasses a spectrum of clinical and pathological
processes manifested by focal asymmetric, transmural, and occasionally
granulomatous inflammation that can affect any segment of the gastrointestinal
tract. Crohn's disease has been characterized by significant morbidity
including abdominal pain, diarrhea, weight lost/malnutrition, a progressive
nature that leads to complications such as fistulas, strictures and abscesses.
Given that no known medical or surgical cure currently exists for CD, the
therapeutic strategy is to reduce symptoms, improve quality of life, reduce
endoscopic evidence of inflammation, and minimize short and long-term toxicity
and complications. Currently, patients with moderate to severe disease who have
failed aminosalicylates or
topical treatments are usually treated with conventional pharmacologic
interventions, which include corticosteroids and immunosuppressive agents.
Patients who do not respond to conventional therapies may be treated with
biologics, such as antiTNF α therapies. However, approximately 40% of patients
do not respond to their first biologic therapy (primary non-responders). Among
patients who initially respond and continue to receive maintenance treatment
for longer durations, approximately 38% become non-responders after 6 months
and approximately 50% become non-responders at 1 year (secondary
non-responders). The available treatment options may also be associated with
some adverse events (AEs) that may limit the use or require close monitoring.
Therefore, there remains a medical need for additional therapeutic options in
CD for patients with inadequate response to or intolerance to conventional
therapies and anti-TNF α agents.
Study objective
This study has been transitioned to CTIS with ID 2023-504951-29-00 check the CTIS register for the current data.
The objective of Substudy 1 (randomized, double-blind, placebo-controlled
maintenance) is 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. The objective of Substudy 2 (long-term
extension [LTE]) is 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.
Study design
This is a phase 3, multicenter, randomized, double-blind, placebo-controlled
maintenance and long-term extension study.
Intervention
All subjects receive upadacitinib or placebo once a day in the form of tablets
(oral) until the end of the study or till premature discontinuation.
Study burden and risks
There will be higher burden for subjects participating in this trial compared
to their standard of care. Subject will be visiting the hospital more
frequently. During these visits study procedures will be performed including
blood sampling and completion of questionnaires. Subjects will be tested for TB
and Subjects will also complete a daily diary. Women of Childbearing Potential
should practice a method of birth control, during the study through at least 30
days after the last dose of study drug and are tested for pregnancy. Subjects
will receive upadacitinib and/or placebo during the study. The most common side
effects reported during studies of upadacitinib were headache, upper chest
infection, common cold, diarrhea, and cough. The proposal to initiate a Phase 3
study in subjects with CD is based on the following supportive findings:
1) demonstrated clinical and endoscopic improvements in the induction
treatment in a Phase 2 dose-ranging study; and
2) safety results were consistent with those known to be associated with JAK
inhibition.
The current Phase 3 Study M14-430 will further evaluate the benefit to risk
profile of upadacitinib as maintenance therapy in subjects with CD who have
inadequately responded are intolerant to conventional or biologic therapies and
have responded to upadacitinib induction treatment. The risks and burden
associated with participating in this study are acceptable in regards to the
potential benefit study subjects could possibly have.
Wegalaan 9
Hoofddorp 2132JD
NL
Wegalaan 9
Hoofddorp 2132JD
NL
Listed location countries
Age
Inclusion criteria
For Substudy 1:
- Subject achieved clinical response in Study M14-431 or Study M14-433.
- Subject completed Week 12 (in subjects who achieve response at Week 12) or
Week 24 (in subjects who achieve response at Week 24) visit and 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
COVID-19 pandemic.
Note: Subjects completing Part 3/Cohort 3 of Study M14-431, who received
open-label Extended Treatment, should enroll in Substudy 2.
For Substudy 2:
- Subject completed Week 52 of the maintenance period of Study M14-430
(Substudy 1).Completion includes the Week 52 endoscopy of Substudy 1. The Week
52 endoscopy may be missing, if the endoscopy cannot be performed during the
COVID-19 pandemic or any state of emergency or pandemic situation.
- 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
For Sub-studies 1 and 2:
- Participant is considered by the investigator, for any reason, to be an
unsuitable candidate for the study.
- Participant who has a known hypersensitivity to upadacitinib or its
excipients, or had an adverse event during Study M14-431 or Substudy 1 or 2 of
Study M14-430 that in the investigator's judgment makes the subject unsuitable
for this study.
- Participant at the final visit of M14-431 or M14-433 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 ongoing
infections undergoing treatment may be enrolled BUT NOT dosed until the
infection treatment has been completed and the infection is cured, based on the
investigator's assessment.
- Participants 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
or 2 of Study M14-430 (Week 52).
Design
Recruitment
Medical products/devices used
Kamer G4-214
Postbus 22660
1100 DD Amsterdam
020 566 7389
mecamc@amsterdamumc.nl
Kamer G4-214
Postbus 22660
1100 DD Amsterdam
020 566 7389
mecamc@amsterdamumc.nl
Kamer G4-214
Postbus 22660
1100 DD Amsterdam
020 566 7389
mecamc@amsterdamumc.nl
Kamer G4-214
Postbus 22660
1100 DD Amsterdam
020 566 7389
mecamc@amsterdamumc.nl
Kamer G4-214
Postbus 22660
1100 DD Amsterdam
020 566 7389
mecamc@amsterdamumc.nl
Kamer G4-214
Postbus 22660
1100 DD Amsterdam
020 566 7389
mecamc@amsterdamumc.nl
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EU-CTR | CTIS2023-504951-29-00 |
| EudraCT | EUCTR2017-001225-41-NL |
| ClinicalTrials.gov | NCT03345823 |
| CCMO | NL62828.018.18 |