Ulcerative Colitis
Conditions
Keywords
Drug Therapy
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.
Interventions
DRUGVedolizumab
Vedolizumab IV infusions
DRUGTofacitinib
Tofacitinib Tablets
Sponsors
Takeda
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
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 with inadequate response, loss of response, or intolerance to conventional UC therapy 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 2 weeks prior to screening endoscopy and must be willing to follow a mandatory taper of corticosteroids from enrollment.
Exclusion criteria
Gastrointestinal
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Achieving Clinical Remission at Week 8 Based on Complete Mayo Score | At Week 8 | Clinical remission based on complete Mayo Score is where a participant achieves complete Mayo Score ≤2 points with no individual subscore \>1 at Week 8. The complete Mayo Clinic Score includes 4 variables: Stool frequency, rectal bleeding, a Physician's Global Index (PGA) and Mayo endoscopic findings (MES). Each variable is scored on a 4-point scale (0-3 points) where 0=none and 3=severe disease and summed to give a total disease activity score (range, 0-12), with higher scores representing more severe disease activity. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Achieving Clinical Remission at Week 52 Based on Complete Mayo Score | At Week 52 | Clinical remission based on complete Mayo Score is where a participant achieves complete Mayo Score ≤2 points with no individual subscore \>1 at Week 8. The complete Mayo Clinic Score includes 4 variables: Stool frequency, rectal bleeding, a Physician's Global Index (PGA) and Mayo endoscopic findings (MES). Each variable is scored on a 4-point scale (0-3 points) where 0=none and 3=severe disease and summed to give a total disease activity score (range, 0-12), with higher scores representing more severe disease activity. |
| Percentage of Participants Achieving Clinical Remission at Weeks 8, 14, and 26 Based on Partial Mayo Score | At Weeks 8, 14 and 26 | Clinical remission based on complete Mayo Score is where a participant achieves complete Mayo Score ≤2 points with no individual subscore \>1. Partial Mayo Score consists of 3 variables of the Mayo Clinic Score: stool frequency, rectal bleeding and PGA. Each variable is scored on a 4-point scale (0-3 points) where 0=none and 3=severe disease. These scores are summed to give a total score range of 0 to 9 where higher scores indicate maximum disease activity. |
| Percentage of Participants Achieving Clinical Response at Weeks 2, 6, 8, 14, 26 and 52 Based on Complete or Partial Mayo Score | At Weeks 2, 6, 8, 14, 26, and 52 | Clinical response based on complete Mayo Score is where a participant achieves a reduction in complete Mayo score of ≥3 points and ≥30% from Baseline or a partial Mayo score of ≥2 points and ≥25% from baseline, if the complete Mayo score was not performed at the visit with an accompanying decrease in rectal bleeding subscore of ≥1 point or absolute rectal bleeding subscore of ≤1 point. The complete Mayo Clinic Score includes 4 variables: Stool frequency, rectal bleeding, a PGA and MES. Each variable is scored on a 4-point scale (0-3 points) where 0=none and 3=severe disease and summed to give a total disease activity score (range, 0-12), with higher scores representing more severe disease activity. |
| Percentage of Participants Achieving Clinical Remission at Week 8 and Week 52 Based on Modified Mayo Score | At Weeks 8 and 52 | Clinical remission based on modified Mayo Score is where a participant achieves component modified Mayo score of ≤2 with modified MES ≤1, rectal bleeding = 0, and stool frequency ≤1. Modified Mayo Score consists of 3 variables: stool frequency, rectal bleeding and MES. Each variable is scored on a 4-point scale (0-3 points) where 0=none and 3=severe disease. These scores are summed to give a total score range of 0 to 9 where higher scores indicate maximum disease activity. |
| Percentage of Participants With Durable Clinical Remission at Week 8 and Week 52 | At Week 8 and Week 52 | Durable clinical remission is defined as the clinical remission at Week 8 and Week 52. Clinical remission is defined as complete Mayo Score of ≤2 points and no individual subscore \>1 point at Weeks 8 and 52. The complete Mayo Clinic Score includes 4 variables: Stool frequency, rectal bleeding, a PGA and MES. Each variable is scored on a 4-point scale (0-3 points) where 0=none and 3=severe disease and summed to give a total disease activity score (range, 0-12), with higher scores representing more severe disease activity. |
| Percentage of Participants Using Oral Corticosteroids at Baseline Achieving Clinical Remission at Week 8 | At Week 8 | Clinical remission is defined as complete Mayo Score of ≤2 points and no individual subscore \>1 point at Week 8. The complete Mayo Clinic Score includes 4 variables: Stool frequency, rectal bleeding, a PGA and MES. Each variable is scored on a 4-point scale (0-3 points) where 0=none and 3=severe disease and summed to give a total disease activity score (range, 0-12), with higher scores representing more severe disease activity. |
| Percentage of Participants With Corticosteroid-Free Clinical Remission at Week 8 | At Week 8 | Corticosteroid-free clinical remission is where a participant achieves corticosteroid-free clinical remission at Week 8. Clinical remission is defined as complete Mayo Score of ≤2 points and no individual subscore \>1 point at Week 8. The complete Mayo Clinic Score includes 4 variables: Stool frequency, rectal bleeding, a PGA and MES. Each variable is scored on a 4-point scale (0-3 points) where 0=none and 3=severe disease and summed to give a total disease activity score (range, 0-12), with higher scores representing more severe disease activity. |
| Percentage of Participants Using Oral Corticosteroids at Baseline Achieving Clinical Remission at Week 52 | At Week 52 | Clinical remission is defined as complete Mayo Score of ≤2 points and no individual subscore \>1 point at Week 52. The complete Mayo Clinic Score includes 4 variables: Stool frequency, rectal bleeding, a PGA and MES. Each variable is scored on a 4-point scale (0-3 points) where 0=none and 3=severe disease and summed to give a total disease activity score (range, 0-12), with higher scores representing more severe disease activity. |
| Percentage of Participants With Corticosteroid-Free Clinical Remission at Week 52 | At Week 52 | Corticosteroid-free clinical remission is where a participant achieves corticosteroid-free clinical remission at Week 52, and was off corticosteroids at least 3 months prior to Week 52. Clinical remission is defined as complete Mayo Score of ≤2 points and no individual subscore \>1 point at Week 8. The complete Mayo Clinic Score includes 4 variables: Stool frequency, rectal bleeding, a PGA and MES. Each variable is scored on a 4-point scale (0-3 points) where 0=none and 3=severe disease and summed to give a total disease activity score (range, 0-12), with higher scores representing more severe disease activity. |
| Percentage of Participants Achieving Clinical Response at Week 8 | At Week 8 | Clinical response based on complete Mayo Score is where a participant achieves a reduction in complete Mayo score of ≥3 points and ≥30% from Baseline with an accompanying decrease in rectal bleeding subscore of ≥1 point or absolute rectal bleeding subscore of ≤1 point. The complete Mayo Clinic Score includes 4 variables: Stool frequency, rectal bleeding, a PGA and MES. Each variable is scored on a 4-point scale (0-3 points) where 0=none and 3=severe disease and summed to give a total disease activity score (range, 0-12), with higher scores representing more severe disease activity. |
| Percentage of Participants With Mucosal Healing Based on MES at Week 52 | At Week 52 | Mucosal healing is defined as MES ≤1 point at Week 52. MES is a subscale of the Mayo score, an instrument designed to measure disease activity of UC. The subscale is graded from 0 to 3 based on the findings on endoscopy were 0= Normal appearance of mucosa, 1=mild disease (erythema, decreased vascular pattern), 2=moderate disease (marked erythema, lack of vascular pattern, friability, erosions), 3=severe disease (spontaneous bleeding, ulceration). Higher scores indicate more severe disease. |
| Percentage of Participants With Histological Remission Based on Geboes Score at Week 52 | At Week 52 | Histological remission is defined as Geboes score \<2 at Week 52. The Geboes score is a histological grading system for assessing histological disease activity in UC. The Geboes score evaluates 7 histological features. It consists of 6 grades (0-6). Each of the grades is divided into subgrades, based on the severity of tissue abnormalities or the extent of inflammatory cell infiltration. The Geboes score ranges from 0.0 to 5.4, and higher grades are indicative of more severe disease activity. |
| Change in C-Reactive Protein Levels (CRP) From Baseline | Baseline to Weeks 2, 6, 8, 14, 26, 42 and 52 | CRP is a useful marker of inflammation in participants with inflammatory bowel disease (IBD). In participants with UC, elevated CRP has been associated with severe clinical activity. |
| Change in Fecal Calprotectin Concentrations From Baseline | Baseline to Weeks 2, 6, 8, 14, 26, 42 and 52 | Fecal calprotectin is a biomarker for intestinal inflammatory activity. |
| Change in Inflammatory Bowel Disease Questionnaire (IBDQ) Score From Baseline | At Weeks 8, 26 and 52 | The IBDQ is an instrument used to assess quality of life in adult participants with inflammatory bowel disease (IBD). It includes 32 questions on 4 domains of Health-Related Quality-of-Life (HRQOL): Bowel Systems (10 items), Emotional Function (12 items), Social Function (5 items), and Systemic Function (5 items). Participants are asked to recall symptoms and quality of life from the last 2 weeks and rate each item on a 7-point Likert scale (1=worst to 7=best). A total IBDQ score is calculated by summing the scores from each domain; the total IBDQ score ranges from 32 to 224, with lower scores reflecting worse HRQOL. A positive change from Baseline indicates improvement. |
| Change in Functional Assessment of Chronic Illness Therapy Fatigue (FACIT-F) Score From Baseline | At Weeks 8, 26 and 52 | The FACIT-F is a validated, 13-item questionnaire to assess fatigue in participants with a variety of chronic illnesses, including participants with IBD. Items are rated on a 5-point Likert scale and the total score ranges from 0 to 52 with lower scores representing greater fatigue. |
| Number of Participants With Adverse Events (AEs), Adverse Events of Special Interest (AESIs) and Serious Adverse Events (SAEs) | Up to 76 Weeks | An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of the study intervention, whether or not the occurrence is considered related to the study intervention. |
| Number of Participants With Clinically Significant Change in Vital Signs From Baseline | Up to 76 Weeks | Vital signs will include body temperature, respiratory rate, blood pressure (resting more than 5 minutes), and pulse (resting more than 5 minutes). |
| Number of Participants With Clinically Significant Physical Examination Findings | At Baseline and From Week 14 to Week 72 | A baseline physical examination (defined as the assessment before first dose of study medication) will consist of the following body systems: general appearance; HEENT (head, eyes, ears, nose, and throat); cardiovascular system; respiratory system; gastrointestinal system; dermatologic system; extremities; musculoskeletal system; nervous system; lymph nodes; and other. All subsequent physical examinations will assess clinically significant changes from the assessment prior to first dose examination. |
| Number of Participants With Markedly Abnormal Laboratory Values | Up to Week 76 | Standard laboratory tests will include clinical chemistry, hematology, coagulation and urinalysis. |
Countries
Canada, United States
Contacts
CONTACTTakeda Contact
STUDY_DIRECTORStudy Director
Takeda
Outcome results
None listed