Overview
A Study of Vedolizumab With Tofacitinib in Adults With Ulcerative Colitis (UC)
Status:
Not yet recruiting
Not yet recruiting
Trial end date:
2027-07-09
2027-07-09
Target enrollment:
0
0
Participant gender:
All
All
Summary
The main aim of this study is to learn about the effect of treatment with vedolizumab IV (vedolizumab) together with tofacitinib in adults with moderate and severe ulcerative colitis (UC). Another aim is to learn about treatment with Vedolizumab alone after the double treatment. All participants will receive vedolizumab together with tofacitinib for 8 weeks and will be checked for response. Participants who show a response to the treatment after 8 weeks will be treated with vedolizumab alone for an additional 44 weeks. Each participant will be followed up for at least 26 weeks after the last dose of vedolizumab.Phase:
Phase 4Accepts Healthy Volunteers?
NoDetails
Lead Sponsor:
TakedaTreatments:
Tofacitinib
Vedolizumab
Criteria
Inclusion Criteria:1. Has a confirmed diagnosis of UC established at least 3 months prior to screening, by
clinical and endoscopic evidence and corroborated by a histopathology report.
2. Has moderately to severely active UC as determined by a complete Mayo score [including
physician's global assessment (PGA)] of 6 to 12 with a rectal bleeding subscore ≥>1
and a centrally assessed endoscopic subscore ≥2 at screening.
3. Has evidence of UC extending proximally to the rectum [≥15 centimeter (cm) of involved
colon].
4. Participants with extensive colitis or pancolitis of >8 years duration or left sided
colitis >12 years duration must have documented evidence that a surveillance
colonoscopy was performed within 12 months of the initial screening visit.
5. Participants with a family history of colorectal cancer, personal history of increased
colorectal cancer risk, age >50 years, or other known risk factors must be up to date
on colorectal cancer surveillance.
6. Has demonstrated an inadequate response to, loss of response to, or intolerance to no
more than 2 TNF antagonists.
7. If using corticosteroids must be on a stable dose of oral corticosteroids up to a
maximum of 20 milligrams per day (mg/day) of prednisone or equivalent for at least 4
weeks prior to screening endoscopy and must be willing to follow a mandatory taper of
corticosteroids from enrollment.
Exclusion Criteria:
Gastrointestinal Exclusion criteria:
1. Has any of the following UC-related complications:
1. Acute severe UC.
2. The participant has had extensive colonic resection, subtotal or total colectomy.
3. The participant has clinical evidence of abdominal abscess or toxic megacolon.
4. The participant has had ileostomy, colostomy, or known fixed symptomatic stenosis
of the intestine.
5. Short bowel syndrome.
2. Has Crohn's colitis, indeterminate colitis, ischemic colitis, nonsteroidal
anti-inflammatory drug (NSAID) induced colitis, idiopathic colitis (i.e, colitis not
consistent with UC), radiation colitis, microscopic colitis, colonic mucosal
dysplasia, or untreated bile acid malabsorption.
3. Has uncontrolled primary sclerosing cholangitis.
Infectious Disease Exclusion Criteria:
1. Has any evidence of an active infection during screening.
2. Has active or latent tuberculosis (TB), regardless of treatment history, as evidenced
by any of the following:
a. History of TB. b. A diagnostic TB test performed during screening that is positive,
as defined by: i. A positive QuantiFERON test or 2 successive indeterminate
QuantiFERON tests or ii. A tuberculin skin test reaction ≥10 mm (≥5 mm in subjects
receiving the equivalent of >15 mg/day prednisone).
3. A positive test for hepatitis B virus (HBV).
4. A positive test for hepatitis C virus (HCV).
5. Evidence of, or treatment for, Clostridium difficile infection or other intestinal
pathogen within 28 days prior to first dose of study treatment.
7. Evidence of active Cytomegalovirus (CMV) infection at screening.
Medication exclusion criteria:
1. Has received immunomodulators (eg, 6-mercaptopurine, azathioprine, and methotrexate)
within 4 weeks prior to first dose or immunosuppressants (eg, cyclosporine,
tacrolimus) within 8 weeks prior to first dose.
2. Any medicinal product, herbal medication, or natural health product which might
interfere with cytochrome P450 genotype 3A4 (CYP3A4) within 2 weeks prior to
enrollment.
3. Has received any of the following medical therapies for UC:
1. IV antibiotics within 8 weeks prior to enrollment.
2. Any rectal therapy for treatment of UC within 2 weeks prior to screening
endoscopy.
3. NSAIDs as long-term treatment, defined as use for at least 4 days a week each
month (>100 milligrams (mg) daily or acetaminophen and aspirin >325 mg daily.)
4. Has received a live virus or live bacterial vaccine within 4 weeks prior to
enrollment, or planned vaccination during the study and for 12 weeks after last dose.
General Exclusion Criteria:
1. Has any of the following cardiovascular or thrombotic conditions:
1. Recent (within past 6 months) cerebrovascular accident, myocardial infarction, or
coronary stenting.
2. Recent (within past 6 months) moderate to severe congestive heart failure (New
York Heart Association class III or IV).
3. Prior history of thrombotic events, including deep vein thrombosis and pulmonary
embolism.
4. Known inherited conditions that predispose to hypercoagulability.
2. History of lymphoproliferative disease, including lymphoma, or signs and symptoms
suggestive of possible lymphoproliferative disease, such as lymphadenopathy and/or
splenomegaly.
3. A surgical procedure requiring general anesthesia within 3 months prior to screening
or is planning to undergo major surgery during the study period.
4. Any investigational procedure ≤4 weeks prior to screening.