vedolizumab-4026

JRCT ID: jRCTs011200009

Registered date:06/11/2020

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: Subjects with UC
• Date of first enrollment: 08/04/2021
• Target sample size: 30
• Study type: Interventional
• Intervention(s): Vedolizumab 300 mg is administered at Week 0, 2, 6 and every 8 weeks thereafter. Treatment duration is 46 weeks.

Outcome(s)

• Primary Outcome: Correlation between the concentrations of vedolizumab in the colonic tissue and in the serum, and clinical remission at Week 54

Secondary Outcome

Correlation between the concentrations of vedolizumab in the colonic tissue and in the serum, and clinical remission at Week 14
Correlation between the concentrations of vedolizumab in the colonic tissue (inflamed/non inflamed) and in the serum, and mucosal healing at Week 14 and 54
Correlation between the colonic tissue (inflamed/non inflamed) and serum concentrations of vedolizumab, alpha4beta7 integrin receptor occupancy and clinical outcomes at Week 14 and 54
Correlation between the concentrations of vedolizumab in the colonic tissue (inflamed/non inflamed) and in the serum at Week 14 and 54
Correlation between the concentrations of vedolizumab in the colonic tissue (inflamed/non inflamed) and in the serum and clinical outcomes in subjects with or without previous exposure to TNFalpha antagonist at Week 14 and 54
Correlation between the concentrations of vedolizumab in the colonic tissue (inflamed/non inflamed) and in the serum, alpha4beta7 integrin receptor occupancy and clinical outcomes in subjects with or without previous exposure to TNFalpha antagonist at Week 14 and 54
Correlation between the colonic tissue transcriptome and clinical outcomes at Week 14 and 54
Correlation between the concentrations of vedolizumab in the colonic tissue (inflamed/non inflamed) and in the serum and immuno phenotyping of various immune cell populations at Week 14 and 54
Correlation between AVA and clinical outcomes at Week 14 and 54
Concentrations of vedolizumab in the colonic tissue (inflamed/non inflamed) and in the serum at Week 14 and 54
Proportion of subjects achieving clinical remission (complete Mayo score <= 2 and all sub scores <= 1) and mucosal healing (endoscopy Mayo sub-score <= 1) at Week 14 and 54
Concentrations of vedolizumab in the colonic tissue (inflamed/non inflamed) and in the serum in subjects with or without previous exposure to TNFalpha antagonist at Week 14 and 54
Proportion of subjects achieving clinical remission and mucosal healing in subjects with or without previous exposure to TNFalpha antagonist at Week 14 and 54
alpha4beta7 receptors occupancy in various lymphocyte populations in the colonic tissue (inflamed/non inflamed) and in the blood at Week 14 and 54
Proportion of subjects positive for anti vedolizumab antibody (AVA also called human antihuman antibody HAHA) at Baseline, Week 14 and 54
Proportion of subjects positive for neutralizing AVA at Baseline, Week 14 and 54
Transcriptome analysis of the colonic tissue at Week 0 (baseline), 14 and 54
Immuno phenotyping of various immune cell populations at Week 0 (baseline), 14 and 54

Key inclusion & exclusion criteria

• Age minimum: >= 20age old
• Age maximum: <= 80age old
• Gender: Both

Include criteria

1. Subject who is capable of understanding and complying with protocol requirements in the opinion of the investigator.
2. Subject who signs and dates a written informed consent form prior to the initiation of any study procedures.
3. Subjects who have had a diagnosis of moderate to severe UC for at least 3 months prior to enrollment.
4. Subjects with complete Mayo score of 6 to 12 and endoscopic subscore of>=2 within 10 days before the initial administration of vedolizumab.
5. Subjects who met the following treatment failure criteria with at least one of the following agents:
Corticosteroids
Resistance subjects whose response was inadequate after treatment of>=40 mg day for>=1 week (oral or intravenous IV) or 30 to 40 mg day for>=2 weeks (oral or IV) or topical therapy for >=2 weeks in case of distal UC.
Dependence subjects for which it was difficult to reduce the dosage to <10 mg day due to recurrence during gradual dose reduction (oral or IV) or for which it was difficult to discontinue topical therapy.
Intolerance subjects who were unable to receive continuous treatment due to adverse reactions (e.g. Cushings syndrome osteopenia osteoporosis hyperglycemia insomnia infection).
Immunomodulators (azathioprine AZA or 6 mercaptopurine 6 MP)
Refractory subjects whose response was inadequate after treatment for>=12 weeks.
Intolerance subjects who were unable to receive continuous treatment due to adverse reactions(e.g. nausea vomiting abdominal pain pancreatitis liver function test abnormalities lymphopenia thiopurine S methyltransferase genetic mutation infection).
TNFalpha antagonist
Inadequate response subjects whose response was inadequate after the induction therapy in the dosage described in the package insert.
Loss of response subjects who had recurrence during the scheduled maintenance therapy after achievement of clinical response (those who withdrew for other reasons than relapse is not applicable here).
Intolerance subjects who were unable to receive continuous treatment due to adverse reactions (e.g. infusion related reaction demyelination congestive heart failure infection).
6. Subject aged 20 to 80 years at informed consent.

Exclude criteria

1. Subjects who had extensive colonic resection subtotal or total colectomy
2. Subjects who are classified as proctitis UC (inflammation is limited to the rectum)
3. Subjects who had ileostomy, colostomy or symptomatic intestinal stricture
4. Subjects who had received any of the following biologic within the designated period before the initial administration of vedolizumab: infliximab (8 weeks before) adalimumab (2 weeks before) golimumab (4weeks before) JAK inhibitor (1 week before) ustekinumab (8 weeks before)
5. Subjects who had prior exposure to vedolizumab natalizumab efalizumab or rituximab (any time before)
6. Subjects who had any evidence of an active infection within 1 month prior to the first administration of vedolizumab
7. Subject with a history of hypersensitivity or allergies to vedolizumab or its components (subjects with contraindication in the vedolizumab package insert)
8. Subjects with concurrent malignancies who are deemed unsuitable for enrollment by the investigator
9. Patients who have been determined to be inappropriate as subjects in the study by the investigator

Related Information

• Primary Sponsor: Fujiya Mikihiro
• Secondary Sponsor: Takeda Pharmaceutical Company Limited (Takeda)