The objective of this study is to evaluate the efficacy and safety of upadacitinib compared to placebo as induction therapy in participants with moderately and severely active Crohn's disease (CD).
ID
Source
Brief title
Condition
- Gastrointestinal inflammatory conditions
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Proportion of subjects with clinical remission per PROs at Week 12
Proportion of subjects with endoscopic response at Week 12
Secondary outcome
1. Proportion of subjects with clinical remission per CDAI (CDAI < 150)
2. Proportion of subjects with clinical remission at Week 4
3. Proportion of subjects with endoscopic remission at Week 12
4. Proportion of subjects who discontinue corticosteroid use for CD and
achieve clinical remission at Week 12, in subjects taking corticosteroids for
CD at Baseline
5. Change from Baseline in Functional Assessment of Chronic Illness
Therapy-Fatigue at Week 12
6. Change from Baseline in Inflammatory Bowel Disease Questionnaire (IBDQ) at
Week 12
7. Proportion of subjects achieving CR-100 at Week 2
8. Proportion of subjects achieving CR-100 at Week 12
9. Proportion of subjects with hospitalizations due to CD during the 12 week
double-blind induction period
10. Proportion of subjects with resolution of extra-intestinal manifestation
(EIM) at Week 12, in subjects with EIM at Baseline.
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
The objective of this study is to evaluate the efficacy and safety of
upadacitinib compared to placebo as induction therapy in participants with
moderately and severely active Crohn's disease (CD).
Study design
This is a phase 3, multicenter, randomized, double-blind, placebo-controlled
induction 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. Subjects 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, Hepatitis C/Hepatitis B and Human immunodeficiency virus (HIV) 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 M14-433 will further evaluate the benefit to risk
profile of upadacitinib in subjects with CD who have inadequately responded are
intolerant to conventional therapies. 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
- Confirmed diagnosis of CD for at least 3 months prior to Baseline.
Appropriate documentation of biopsy results consistent with the diagnosis of
CD, in the assessment of the investigator, must be available.
- Evidence of mucosal inflammation based on the Simplified Endoscopic Score for
Crohn's disease (SES-CD) on an endoscopy confirmed by a central reader.
- Confirmed diagnosis of moderate to severe CD as assessed by stool frequency
(SF), abdominal pain (AP) score.
- Demonstrated an inadequate response or intolerance to one or more
conventional and/or biologic therapies.
Note: Participants who have received prior biologic for up to 1 year but have
not failed may be enrolled; however, participants must have discontinued the
biologic for reasons other than inadequate response or intolerance (e.g.,
change of insurance, well controlled disease),
- If female, subject must meet the contraception recommendations.
Exclusion criteria
- Subject with a current diagnosis of ulcerative colitis or indeterminate
colitis.
- Subject not on stable doses of CD related antibiotics, oral aminosalicylates,
corticosteroids or methotrexate (MTX).
- Subject with the following known complications of CD: abscess (abdominal or
peri-anal), > 2 entire missing segments of the following 5 segments: terminal
ileum, right colon, transverse colon, sigmoid and left colon, and
rectum,symptomatic bowel strictures, fulminant colitis, toxic megacolon, or any
other manifestation that might require surgery while enrolled in the study.
- Subject with ostomy or ileoanal pouch
- Subject diagnosed with conditions that could interfere with drug absorption
including but not limited to short gut or short bowel syndrome
- Subject with surgical bowel resection within the past 3 months prior to
baseline, or a history of >3 bowel resections.
- Subject laboratory and other analyses show abnormal results.
Design
Recruitment
Medical products/devices used
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 |
|---|---|
| EudraCT | EUCTR2017-001240-35-NL |
| ClinicalTrials.gov | NCT03345849 |
| CCMO | NL62827.018.18 |