The objective of Study M14-675 (Phase 3 induction) is to evaluate the efficacy and safety of upadacitinib 45 mg once daily (QD) compared to placebo in inducing clinical remission (per Adapted Mayo score) in subjects with moderately to severely…
ID
Source
Brief title
Condition
- Gastrointestinal inflammatory conditions
- Autoimmune disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary endpoint for Study M14-675 is the proportion of subjects who
achieve clinical remission per Adapted Mayo score (defined as SFS <= 1 and not
greater than baseline, RBS of 0, and endoscopic sub score <= 1) at Week 8.
Secondary outcome
1. Proportion of subjects with endoscopic improvement at Week 8
2. Proportion of subjects with endoscopic remission at Week 8
3. Proportion of subjects achieving clinical response per Adapted Mayo Score at
Week 8
4. Proportion of subjects achieving clinical response per Partial Adapted Mayo
score (defined as decrease from Baseline = 1 points and = 30% from Baseline,
PLUS a decrease in RBS = 1 or an absolute RBS = 1 ) at Week 2
5. Proportion of subjects achieving histologic-encoscopic mucosal improvement
at Week 8
6. Proportion of subjects who reported no bowel urgency at Week 8
7. Proportion of subjects who reported no abdominal pain at Week 8
8. Proportion of subjects who achieved histologic improvement at Week 8
9. Change from Baseline in IBDQ total score at week 8
10. Proportion of subjects with mucosal healing at Week 8
11. Change from Baseline in FACIT-F score at week 8
Background summary
UC is a chronic, relapsing inflammatory disease of the large intestine
characterized by inflammation and ulceration of mainly the mucosal and
occasionally submucosal intestinal layers. The hallmark clinical symptoms
include bloody diarrhea associated with rectal urgency and tenesmus. The most
severe intestinal manifestations of UC are toxic megacolon and perforation.
Patients with UC are at an increased risk for colon cancer, and the risk
increases with the duration of disease as well as extent of colon affected by
the disease.
The aim of medical treatment in UC is to control inflammation and reduce
symptoms. Available pharmaceutical therapies are limited, do not always
completely abate the inflammatory process, and may have significant adverse
effects.
Upadacitinib is a novel selective Janus kinase (JAK) 1 inhibitor. JAK1
inhibition blocks the signaling of many important pro-inflammatory cytokines.
Through modulation of these pro-inflammatory cytokine pathways, upadacitinib
offers the potential for effective treatment of inflammatory or autoimmune
disorders. The clinical hypothesis is that, based on the differentiated
selectivity profile for JAK inhibition, upadacitinib could demonstrate an
improved benefit/risk profile compared to other less selective JAK inhibitors
or other therapeutic strategies for patients with inflammatory diseases.
Study objective
The objective of Study M14-675 (Phase 3 induction) is to evaluate the efficacy
and safety of upadacitinib 45 mg once daily (QD) compared to placebo in
inducing clinical remission (per Adapted Mayo score) in subjects with
moderately to severely active ulcerative colitis.
Study design
Study M14-675 is a Phase 3, multicenter, randomized, double-blind,
placebo-controlled study designed to evaluate the efficacy and safety of oral
administration of a once daily dose of upadacitinib 45 mg QD compared to
placebo as induction therapy for up to 16 weeks in subjects with moderately to
severely active UC.
At the end of either Week 8 (Part 1) or Week 16 (Part 2), if subjects are
eligible, they will be offered an opportunity to participate in Study M14-234
Substudy 3 which is a Phase 3 study designed to evaluate the efficacy and
safety of oral administration of upadacitinib 15 mg or 30 mg compared to
placebo as maintenance therapy in subjects with moderately to severely active
UC who achieved clinical response following induction with upadacitinib in
Study M14-675.
Subjects who consent and meet all of the inclusion criteria and none of the
exclusion criteria will be enrolled into Study M14-675, which consists of two
parts: (Part 1) a randomized, double-blind, placebo-controlled 8-week induction
study; and (Part 2) an 8-week Extended Treatment Period for clinical
non-responders from Part 1.
Study burden and risks
There will be higher burden for subjects participating in this study 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 endoscopies. Subjects will be tested for TB, Hepatitis
C/Hepatitis B and HIV. 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.
The most common reported AEs were: headache, upper chest infection, common
cold, diarrhea, and cough.
Knollstrasse 70
Ludwigshafen 67061
DE
Knollstrasse 70
Ludwigshafen 67061
DE
Listed location countries
Age
Inclusion criteria
1. Male or female between 16 and 75 years of age at Baseline.
- Adolescent subjects at the age of 16 and 17 years old will be enrolled if
approved by the country or regulatory/health authority. If these approvals have
not been granted, only subjects = 18 years old will be enrolled.
- Adolescent subjects at the age of 16 and 17 years old must weigh = 40 kg and
meet the definition of Tanner Stage 5 (refer to Appendix J) at the screening
Visit.
2. Diagnosis of ulcerative colitis for 90 days or greater prior to Baseline,
confirmed by colonoscopy
3. Moderately to severely active ulcerative colitis
4. Demonstrated an inadequate response to, loss of response to, or intolerance
to immunosuppressants, corticosteroids or biologic therapies
5. Negative pregnancy test for female subjects of childbearing potential
Exclusion criteria
1. Subject with current diagnosis of Crohn's disease (CD) or diagnosis of
indeterminate colitis (IC).
2. Current diagnosis of fulminant colitis and/or toxic megacolon.
3. Subject with disease limited to the rectum (ulcerative proctitis) during the
screening endoscopy.
4. Received cyclosporine, tacrolimus, mycophenolate mofetil, or thalidomide
within 30 days prior to Baseline.
5. Subject who received azathioprine or 6-mercaptopurine within 10 days of
Baseline.
6. Received intravenous corticosteroids within 14 days prior to Screening or
during the Screening Period.
7. Subject with previous exposure to JAK inhibitor.
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 | EUCTR2016-000642-62-NL |
| ClinicalTrials.gov | NCT03653026 |
| CCMO | NL66900.018.18 |