Vedolizumab Dual Targeted Therapy with Tofacitinib in Ulcerative Colitis

What is the Purpose of this Study?

The purpose of this study is to determine whether combining medications for ulcerative colitis (vedolizumab with tofacitinib) is safe and improves symptoms of the disease. This treatment combination is referred to as “dual targeted therapy” and includes vedolizumab given by intravenous (IV) infusion and tofacitinib tablet. Treatment will consist of an 8-week dual therapy period and then a 44 week vedolizumab monotherapy (single therapy) treatment period. Study procedures include physical exams, laboratory tests, endoscopies, and completion of questionnaires. Vedolizumab works by blocking certain inflammation-causing cells, including white blood cells, from entering the gut. This can help to control the inflammation caused by ulcerative colitis. Tofacitinib works by blocking the effect of certain enzymes, which are cells involved in the inflammation that causes the symptoms of ulcerative colitis. All participants will receive vedolizumab and tofacitinib. Both vedolizumab and tofacitinib are approved by the U.S. Food and Drug Administration (FDA) as individual treatments for ulcerative colitis, but their combined use for the treatment of ulcerative colitis is investigational.

Eligibility

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.

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:

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.
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.
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.
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.

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Where can I participate?

Beverly

More about this Clinical Trial

What is the full name of this clinical trial?

An Open-Label, Phase 4, Single-Arm, Multicenter Study to Evaluate the Induction of Response and Remission of Vedolizumab Dual Targeted Therapy with Tofacitinib in Adult Patients with Moderately to Severely Active Ulcerative Colitis

Study Details

Disease Type/Condition

Other

Principal Investigator

Yarur, Andres

Co-Investigators

Andrea Banty, Gil Melmed, Susie Lee, Teddy Solomon

Age Group

Adult

Phase

IRB Number

STUDY00003166

ClinicalTrials.gov ID

NCT06095128

Key Eligibility

ClinicalTrials.gov

How do I learn more about this study?

clinicaltrials@cshs.org