Crohn's Disease, Ulcerative Colitis
Conditions
Keywords
Drug therapy
Brief summary
The purpose of this study is to assess the bioavailability and pharmacokinetics (PK) of multiple doses of vedolizumab subcutaneous (SC) compared to vedolizumab intravenous (IV).
Detailed description
The drug being tested in this study is called vedolizumab. Vedolizumab is being tested to determine its availability and reaction in the body of people who have moderately to severely active Ulcerative Colitis (UC) or Crohn's Disease (CD). This study will look at the availability and reaction of vedolizumab in people who are administered the treatment subcutaneously (SC) compared people who are administered the treatment intravenously (IV). The study will enroll approximately 200 patients with moderately to severely active UC or CD. Participants will be randomly assigned (by chance, like flipping a coin) to one of the five treatment groups: * vedolizumab 300 mg IV * vedolizumab 300 mg IV and vedolizumab 160 mg SC * vedolizumab 300 mg IV and vedolizumab 108 mg SC * vedolizumab 480 mg SC and vedolizumab 160 mg SC * vedolizumab 324 mg SC and vedolizumab 108 mg SC All participants will receive one of the treatments they are assigned to at various treatment visits throughout the study. This multi-centre trial will be conducted in North America, Europe and Asia. The overall time to participate in this study is approximately 41 weeks in addition to a follow-up survey that will be administered every 6 months for 2 years. Participants will make 16 visits to the clinic, including a safety follow-up assessment 18 weeks after last dose of study drug.
Interventions
DRUGVedolizumab intravenous injection
Vedolizumab intravenous injection
DRUGVedolizumab subcutaneous injection
Vedolizumab subcutaneous injection
Sponsors
Takeda
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
General Inclusion Criteria 1. In the opinion of the investigator, the participant is capable of understanding and complying with protocol requirements. 2. The participant or, when applicable, the participant's legally acceptable representative signs and dates a written, informed consent form and any required privacy authorization prior to the initiation of any study procedure. 3. Is aged 18 to 80 years, inclusive. 4. The male or female participant is voluntarily able to give informed consent. 5. A male participant who is nonsterilized and sexually active with a female partner of childbearing potential agrees to use adequate contraception from signing of informed consent throughout the duration of the study and for 18 weeks after last dose. 6. A female participant of childbearing potential who is sexually active with a nonsterilized male partner agrees to use routinely adequate contraception from signing of informed consent throughout the duration of the study and for 18 weeks after last dose. Inclusion Criteria for Ulcerative Colitis Participants 7. Has a diagnosis of ulcerative colitis (UC) established at least 3 months prior to randomization by clinical and endoscopic evidence and corroborated by a histopathology report. 8. Has moderately to severely active UC as determined by a partial Mayo score of 3 to 9 within 7 days prior to the first dose of study drug. 9. Has evidence of UC extending proximal to the rectum (≥15 cm of involved colon). 10. Participants with extensive colitis or pancolitis of \>8 years duration or left-sided colitis of \>12 years duration must have documented evidence that a surveillance colonoscopy with random and targeted biopsies was performed within 18 months of the initial screening visit (may be performed during screening). 11. Participants with a family history of colorectal cancer, personal history of increased colorectal cancer risk, age \>50 years, or other known risk factor for colorectal cancer must be up-to-date on colorectal cancer surveillance (may be performed during screening). 12. Participants may be receiving a therapeutic dose of the following drugs: 1. Oral or topical (rectal) 5-aminosalicylate (5-ASA) compounds provided that the dose has been stable for the 2 weeks immediately prior to randomization; 2. Oral corticosteroid therapy (prednisone at a stable dose ≤30 mg/day, budesonide at a dose ≤9 mg/day or equivalent steroid) provided that the dose has been stable for the 4 weeks immediately prior to randomization if corticosteroids have just been initiated, or for the 2 weeks immediately prior to randomization if corticosteroids are being tapered; 3. Topical (rectal) corticosteroid enemas/suppositories; 4. Azathioprine or 6-mercaptopurin provided that the dose has been stable for the 8 weeks immediately prior to randomization; 5. Antidiarrheals (eg, loperamide, diphenoxylate with atropine) for control of chronic diarrhea; 6. Probiotics (eg, Culturelle, S. boulardii) provided that the dose has been stable for the 2 weeks immediately prior to randomization; 7. Antibiotics used for the treatment of inflammatory bowel disease (IBD) (ie, ciprofloxacin, metronidazole). Inclusion Criteria for Crohn's Disease Participants 13. Has a diagnosis of Crohn's Disease (CD) established at least 3 months prior to randomization by clinical and endoscopic evidence and corroborated by a histopathology report. Cases of CD established at least 3 months prior to randomization for which a histopathology report is not available will be considered based on the weight of the evidence supporting the diagnosis and excluding other potential diagnoses, and must be discussed with the sponsor on a case-by-case basis prior to randomization. 14. Has moderately to severely active CD as determined by Crohn's Disease Activity Index (CDAI) score of 220 to 450 within 7 days prior to the first dose of study drug and 1 of the following: 1. C-reactive protein (CRP) level \>2.87 mg/L during the Screening Period, OR; 2. Ileocolonoscopy with photographic documentation of a minimum of 3 nonanastomotic ulcerations (each \>0.5 cm in diameter) or 10 aphthous ulcerations (involving a minimum of 10 contiguous cm of intestine) consistent with CD, within 4 months prior to randomization, OR; 3. Fecal calprotectin \>250 mcg/g stool during the Screening Period in conjunction with Computed Tomography (CT) enterography, magnetic resonance (MR) enterography, contrast-enhanced small bowel radiography, or wireless capsule endoscopy revealing Crohn's ulcerations (aphthae not sufficient), within 4 months prior to screening (participants with evidence of fixed stenosis or small bowel stenosis with prestenotic dilation should not be included). 15. Has CD involvement of the ileum and/or colon, at a minimum. 16. Participants with extensive colitis or pancolitis of \>8 years duration or limited colitis of \>12 years duration must have documented evidence that a surveillance colonoscopy with random and targeted biopsies was performed within 18 months of randomization (may be performed during screening). 17. Participants with a family history of colorectal cancer, personal history of increased colorectal cancer risk, age \>50 years, or other known risk factor for colorectal cancer must be up-to-date on colorectal cancer surveillance (may be performed during screening). 18. Participants may be receiving a therapeutic dose of the following drugs: 1. Oral or topical (rectal) 5-ASA compounds provided that the dose has been stable for the 2 weeks immediately prior to randomization; 2. Oral corticosteroid therapy (prednisone at a stable dose ≤30 mg/day, budesonide at a dose ≤9 mg/day, or equivalent steroid) provided that the dose has been stable for the 4 weeks immediately prior to randomization if corticosteroids have just been initiated, or for the 2 weeks immediately prior to randomization if corticosteroids are being tapered; 3. Topical (rectal) corticosteroid enemas/suppositories; 4. Antibiotics used for the treatment of IBD (ie, ciprofloxacin, metronidazole); 5. Azathioprine or 6-mercaptopurin provided that the dose has been stable for the 8 weeks immediately prior to randomization; 6. Methotrexate provided that the dose has been stable for the 8 weeks immediately prior to randomization; 7. Antidiarrheals (eg, loperamide, diphenoxylate with atropine) for control of chronic diarrhea; 8. Probiotics (eg, Culturelle, S. boulardii) provided that the dose has been stable for the 2 weeks immediately prior to randomization.
Exclusion criteria
Gastrointestinal
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Average Concentration of Vedolizumab Over the Dosing Interval at Steady-State (Cavg, ss) | Week 0 up to Week 22 | Cavg, ss is defined as the average concentration over the dosing interval at steady-state, calculated as area under the serum concentration-time curve over the dosing interval at steady-state(AUCss)/Tau, where Tau is the dosing interval. |
| Average Concentration of Vedolizumab Over the Dosing Interval from Week 0 to Week 6 (Cavg[wk0-6]) | Week 0 to Week 6 | Area under the serum concentration-time curve from Week 0 to Week 6, calculated using the linear trapezoidal rule. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants with Positive Human Antihuman Antibody (HAHA) During the Study | Pre-dose at Weeks 0, 2, 6, 10, 18, 22 and 38 | — |
| Percentage of Participants with Positive Neutralizing Human Antihuman Antibody (HAHA) During the Study | Pre-dose at Weeks 0, 2, 6, 10, 18, 22 and 38 | Only participants with positive HAHA will be evaluated for positive neutralizing HAHA. |
| Percent Saturation of Mucosal Addressin Cell Adhesion Molecule-1 (MAdCAM-1) at Week 6 | Week 6 | — |
| Percent Saturation of Mucosal Addressin Cell Adhesion Molecule-1 (MAdCAM-1) at Week 22 | Week 22 | — |
Outcome results
None listed