A Study of Vedolizumab With Tofacitinib in Adults With Ulcerative Colitis (UC)

Takeda

Status and phase: Enrolling; Phase 4

Conditions: Ulcerative Colitis

Treatments: Drug: Tofacitinib; Drug: Vedolizumab

Study type: Interventional

Funder types: Industry

Identifiers

NCT06095128

Vedolizumab-4054

Details and patient eligibility

About

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.

Full description

The drugs being tested in this study are called Vedolizumab and Tofacitinib. Vedolizumab and Tofacitinib dual targeted therapy is being tested to treat people with moderate to severe ulcerative colitis (UC) who have experienced inadequate response, loss of response or intolerance to no more than 2 prior tumor necrosis factor (TNF) antagonists. This study will look at the clinical remission in people who take Vedolizumab and Tofacitinib dual targeted therapy.

The study will enroll approximately 65 patients. All the participants will be enrolled in a single treatment group to receive dual targeted treatment with Vedolizumab and Tofacitinib for the first 8 weeks:

Vedolizumab 300 mg + Tofacitinib 10 mg

Only those participants who show a clinical response at Week 8 will transition to Vedolizumab monotherapy for 44 weeks.

This multi-center trial will be conducted in the United States and Canada. The overall duration of the study is up to 76 weeks. Participants will be followed up for 26 weeks after the last dose of the study drug for safety.

Enrollment: 65 estimated patients

Sex: All

Ages: 18 to 65 years old

Volunteers: No Healthy Volunteers

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.

6. 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.

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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65 participants in 1 patient group

Vedolizumab 300 mg + Tofacitinib 10 mg

Experimental group

Description:

Participants will receive Vedolizumab 300 mg , intravenous (IV) infusion, at Week 0, Week 2 and Week 6 along with Tofacitinib 10 mg, tablets, orally, twice daily from Week 0 to Week 8. Participants with clinical response at Week 8 will transition to receive vedolizumab 300 mg IV infusion every 8 weeks (Q8W) through Week 46.

Treatment:

Drug: Tofacitinib

Drug: Vedolizumab