Clinical trial NCT06095128: A Study of Vedolizumab With Tofacitinib in Adults With Ulcerative Colitis (UC)
Official title: 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 type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: Ulcerative Colitis
Keywords: Drug Therapy
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2023-10-23
Enrollment: 65
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility 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 at least 1, but no more than 2 TNFα antagonists. Participants without prior failure or intolerance to biologics are not eligible. Participants who discontinued TNFα antagonist therapy for reasons other than failure or intolerance (eg, pregnancy) may be eligible after discussion with the medical monitor.

   Note: After the interim analysis, participants without prior exposure to biologics may be enrolled if deemed appropriate. Participants who discontinued biologics for reasons other than failure or intolerance (eg, pregnancy) may be eligible after discussion with the Medical Monitor.
7. If using corticosteroids must be on a stable dose of oral corticosteroids up to a maximum of 40 mg daily of prednisone or 9 mg daily of budesonide, 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 an 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. Participants with a history of colonic mucosal dysplasia are also excluded.
3. Has uncontrolled primary sclerosing cholangitis.

Infectious Disease Exclusion Criteria:

1. Has any evidence of an active systemic infection during screening. Participants with nonsystemic infections (eg, active fungal infection of nail beds) may be eligible, if in the opinion of the investigator, inclusion of the participant will not interfere with the collection or interpretation of study results and poses no risk to the participant.
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 daily 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. Participants who test positive for C. difficile or other intestinal pathogens at screening and receive treatment may be enrolled or rescreened (if required) following confirmation of infection resolution.

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, except for any CYP3A4 modulator used to treat a C. difficile or an intestinal pathogen infection at screening.
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. Chronic NSAID use defined as daily use for \>2 consecutive weeks (Note: occasional use \[\<2 consecutive weeks\] of NSAIDs and acetaminophen \[\<100 mg daily\] for headache, arthritis, myalgias, or menstrual cramps and chronic low dose aspirin use \[81-162.5 mg daily\] for cardiovascular prophylaxis are permitted).
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 that, in the investigator's opinion, may interfere with interpretation of study results.

Primary outcomes:
measure: Percentage of Participants Achieving Clinical Remission at Week 8 Based on Complete Mayo Score
timeFrame: At Week 8
Secondary outcomes:
measure: Percentage of Participants Achieving Clinical Remission at Week 52 Based on Complete Mayo Score
timeFrame: At Week 52
measure: Percentage of Participants Achieving Clinical Remission at Weeks 8, 14, and 26 Based on Partial Mayo Score
timeFrame: At Weeks 8, 14 and 26
measure: Percentage of Participants Achieving Clinical Response at Weeks 2, 6, 8, 14, 26 and 52 Based on Complete or Partial Mayo Score
timeFrame: At Weeks 2, 6, 8, 14, 26, and 52
measure: Percentage of Participants Achieving Clinical Remission at Week 8 and Week 52 Based on Modified Mayo Score
timeFrame: At Weeks 8 and 52
measure: Percentage of Participants With Durable Clinical Remission at Week 8 and Week 52
timeFrame: At Week 8 and Week 52
measure: Percentage of Participants Using Oral Corticosteroids at Baseline Achieving Clinical Remission at Week 8
timeFrame: At Week 8
measure: Percentage of Participants With Corticosteroid-Free Clinical Remission at Week 8
timeFrame: At Week 8
measure: Percentage of Participants Using Oral Corticosteroids at Baseline Achieving Clinical Remission at Week 52
timeFrame: At Week 52
measure: Percentage of Participants With Corticosteroid-Free Clinical Remission at Week 52
timeFrame: At Week 52
measure: Percentage of Participants Achieving Clinical Response at Week 8
timeFrame: At Week 8
measure: Percentage of Participants With Mucosal Healing Based on MES at Week 52
timeFrame: At Week 52
measure: Percentage of Participants With Histological Remission Based on Geboes Score at Week 52
timeFrame: At Week 52
measure: Change in C-Reactive Protein Levels (CRP) From Baseline
timeFrame: Baseline to Weeks 2, 6, 8, 14, 26, 42 and 52
measure: Change in Fecal Calprotectin Concentrations From Baseline
timeFrame: Baseline to Weeks 2, 6, 8, 14, 26, 42 and 52
measure: Change in Inflammatory Bowel Disease Questionnaire (IBDQ) Score From Baseline
timeFrame: At Weeks 8, 26 and 52
measure: Change in Functional Assessment of Chronic Illness Therapy Fatigue (FACIT-F) Score From Baseline
timeFrame: At Weeks 8, 26 and 52
measure: Number of Participants With Adverse Events (AEs), Adverse Events of Special Interest (AESIs) and Serious Adverse Events (SAEs)
timeFrame: Up to 76 Weeks
measure: Number of Participants With Clinically Significant Change in Vital Signs From Baseline
timeFrame: Up to 76 Weeks
measure: Number of Participants With Clinically Significant Physical Examination Findings
timeFrame: At Baseline and From Week 14 to Week 72
measure: Number of Participants With Markedly Abnormal Laboratory Values
timeFrame: Up to Week 76
Other outcomes:
Locations:
city: Dothan
country: United States
facility: Digestive Health Specialsits
state: Alabama
city: Sun City
country: United States
facility: GI Alliance Sun City
state: Arizona
city: Los Angeles
country: United States
facility: Cedars-Sinai Medical Center
state: California
city: Newport Beach
country: United States
facility: Hoag Hospital Newport Beach
state: California
city: Orlando
country: United States
facility: Endoscopic Research Inc
state: Florida
city: Tampa
country: United States
facility: Alliance Clinical Research of Tampa, LLC
state: Florida
city: Roswell
country: United States
facility: Gastroenterology Consultants, P.C.
state: Georgia
city: Chicago
country: United States
facility: University of Chicago Medicine
state: Illinois
city: Glenview
country: United States
facility: GI Alliance - Illinois Gastroenterology Group - Glenview
state: Illinois
city: Gurnee
country: United States
facility: GI Alliance - Illinois Gastroenterology Group LLC - Gurnee
state: Illinois
city: Kansas City
country: United States
facility: University of Kansas Medical Center
state: Kansas
city: Louisville
country: United States
facility: University of Louisville
state: Kentucky
city: Metairie
country: United States
facility: GI Alliance
state: Louisiana
city: Chevy Chase
country: United States
facility: Capital Digestive Care - MGG Group - Chevy Chase Clinical Research
state: Maryland
city: Clinton Township
country: United States
facility: Clinical Research Institute of Michigan, LLC
state: Michigan
city: Ypsilanti
country: United States
facility: Huron Gastroenterology Associates, P.C.
state: Michigan
city: Plymouth
country: United States
facility: MNGI Digestive Health, PA
state: Minnesota
city: Kansas City
country: United States
facility: Mid-America Gastro-Intestinal Consultants
state: Missouri
city: Liberty
country: United States
facility: BVL Clinical Research
state: Missouri
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: New York
country: United States
facility: NYU Langone Health
state: New York
city: New York
country: United States
facility: Weill Cornell Medical College- New York Presbyterian Hospital
state: New York
city: Asheville
country: United States
facility: Digestive Health Partners - Asheville Gastroenterology Associate
state: North Carolina
city: Chapel Hill
country: United States
facility: University of North Carolina
state: North Carolina
city: Cincinnati
country: United States
facility: University of Cincinnati
state: Ohio
city: Columbus
country: United States
facility: Ohio Gastroenterology group, Inc.
state: Ohio
city: Westlake
country: United States
facility: Gastro Intestinal Research Institute of Northern Ohio, LLC.
state: Ohio
city: Wexford
country: United States
facility: Allegheny Health Network
state: Pennsylvania
city: Providence
country: United States
facility: University Gastroenterology
state: Rhode Island
city: Rapid City
country: United States
facility: Rapid City Medical Center, LLP
state: South Dakota
city: Dallas
country: United States
facility: GI Alliance - Digestive Health Associates of Texas
state: Texas
city: Houston
country: United States
facility: The University of Texas Health Science Center at Houston
state: Texas
city: Mansfield
country: United States
facility: GI Alliance - Mansfield
state: Texas
city: San Antonio
country: United States
facility: Gastroenterology Research of San Antonio, LLC
state: Texas
city: Southlake
country: United States
facility: Texas Digestive Disease Consultants (TDDC), Southlake
state: Texas
city: Tyler
country: United States
facility: Tyler Research Institute, LLC
state: Texas
city: Webster
country: United States
facility: GI Alliance - Webster
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah Health
state: Utah
city: Bellevue
country: United States
facility: Washington Gastroenterology- GIA
state: Washington
city: Tacoma
country: United States
facility: Washington Gastroenterology- GIA
state: Washington
city: Barrie
country: Canada
facility: Barrie GI Associates Inc.
state: Ontario
city: London
country: Canada
facility: London Health Sciences Centre
state: Ontario
city: Mississauga
country: Canada
facility: West GTA Endoscopy Inc.
state: Ontario
city: North Bay
country: Canada
facility: Viable Clinical Research - North Bay
state: Ontario
city: North York
country: Canada
facility: Toronto Immune and Digestive Health Institute Inc. (TIDHI)
state: Ontario
city: Oakville
country: Canada
facility: ABP Research Services Corp.
state: Ontario
city: Oshawa
country: Canada
facility: Taunton Surgical Centre
state: Ontario
city: Vaughan
country: Canada
facility: Toronto Digestive Disease Associates (TDDA) Specialty Research
state: Ontario
city: Montreal
country: Canada
facility: McGill University Health Centre Montreal General Hospital
state: Quebec
Study officials:
affiliation: Takeda
name: Study Director
role: STUDY_DIRECTOR
References: