Phase III, Multicenter, Randomized, Double-blinded, Placebo-controlled, Parallel-group Study to Evaluate the Efficacy, Safety, and Pharmacokinetics of Intravenous MLN0002 (300 mg) Infusion in Induction and Maintenance Therapy in Japanese Subjects With Moderate or Severe Ulcerative Colitis
Overview
- Phase
- Phase 3
- Status
- Completed
- Sponsor
- Takeda
- Enrollment
- 292
- Primary Endpoint
- Number of Participants With TEAE Related to Body Weight
Overview
Brief Summary
The purpose of this study is to evaluate efficacy, safety and pharmacokinetics of the vedolizumab (MLN0002) induction and maintenance therapy in Japanese participants with moderate or severe ulcerative colitis (UC).
Detailed Description
This study is a phase 3, multicenter, randomized, double-blinded, placebo-controlled, parallel-group study to examine the efficacy, safety, and pharmacokinetics of MLN0002 (Vedolizumab) in induction and maintenance therapy in Japanese patients with moderately or severely active ulcerative colitis.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Eligibility Criteria
- Ages
- 15 Years to 80 Years (Child, Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •In the opinion of the investigator, a participant is capable of understanding and complying with protocol requirements.
- •A participant who is capable of entering the signature and the date on the informed consent by himself/herself or by the participant's legally acceptable representative, if applicable, prior to initiation of study procedures.
- •A participant aged 15 to 80 (inclusive) at the time of signing the informed consent (regardless of sexes).
- •A male participant, who has no sterilization history and whose female partner has child-bearing potential, who agreed with taking proper contraception during the period from the time of signing the informed consent form through 6 months after the last dose of study drug.
- •A female participant with child-bearing potential (having no history of sterilization or whose last menstruation was within 2 years) whose male partner is not receiving contraceptive treatment, and agreed to take proper contraception during the period from the time of signing on the informed consent form through 6 months after the last dose of the study drug.
- •Participants with diagnosis of total or left-sided ulcerative colitis (UC) based on the Revised Diagnostic Criteria for UC issued by "Research Group for Intractable Inflammatory Bowel Disease Designated as Specified Disease" by the Ministry of Health, Labor and Welfare (MHLW) of Japan (2012) at least 6 months before the start of administration of the study drug.
- •A participant with moderately or severely active UC as determined by baseline complete Mayo score of 6 to 12 (inclusive) with an endoscopic subscore of ≥
- •Participants whose complication of colon cancer or dysplasia had to be ruled out by total colonoscopy at the start of the study drug administration (or the results from total colonoscopy performed within 1 year before giving consent are available), if participants met any of the following criteria; participants with ≥8-year history of total or left-sided colitis, participants aged ≥50 years, or participants with a first-degree family history of colon cancer.
- •Participants meeting the following treatment failure criteria with at least one of the following agents within 5 years before signing on the informed consent:
- •Corticosteroids
Exclusion Criteria
- •Participants whose partial Mayo score decrease by 3 points or more between screening and the start of study drug administration.
- •Participants having or suspected to have abdominal abscess or toxic megacolon.
- •Participants with a history of subtotal or total colectomy.
- •Participants with ileostomy, colostomy, fistula or severe intestinal stenosis.
- •Participants having a treatment history with natalizumab, efalizumab or rituximab.
- •Participants who started oral 5-ASA, probiotics, or oral corticosteroids (≤30 mg/day) within 13 days before the first dose of the study drug. Participants who have used these drugs for at least 14 days before the first dose of the study drug, and who changed dosage of or discontinued these drugs within 13 days before the first dose of the study drug.
- •Participants who have received 5-ASA, corticosteroid enemas/suppositories, corticosteroid IV infusion, oral corticosteroid at \>30 mg/day, drugs for diarrhea-predominant irritable bowel syndrome, or Chinese herbal medicine for the UC treatment (eg, Daikenchuto) within 13 days before the first dose of the study drug.
- •Participants who have used an antidiarrheal drug for 4 or more consecutive days within 13 days before the first dose of the study drug or within 7 days before the first dose of the study drug.
- •Participants who have received AZA or 6-MP within 27 days before the first dose of the study drug However, this will not apply to participants who have used these drugs for 83 or more days before the first dose of the study drug and continued the steady dose administration of the drugs for 27 or more days before the first dose of the study drug.
- •Participants who have received cyclosporine, tacrolimus, methotrexate, tofacitinib or any study drugs of low-molecular compound for UC treatment within 27 days before the first dose of the study drug.
Arms & Interventions
Induction Phase: Cohort 1, Placebo
Vedolizumab placebo-matching, intravenous (IV) infusion, once at Weeks 0, 2 and 6 in the induction phase.
Intervention: Vedolizumab placebo (Drug)
Induction Phase: Cohort 1, Vedolizumab 300 mg
Vedolizumab 300 mg, IV infusion, once at Weeks 0, 2, and 6 in the induction phase.
Intervention: Vedolizumab (Drug)
Induction Phase: Cohort 2, Vedolizumab 300 mg
Vedolizumab 300 mg, IV infusion, once at Weeks 0, 2 and 6 in the induction phase.
Intervention: Vedolizumab (Drug)
Maintenance Phase: Placebo
Vedolizumab placebo-matching, IV infusion, once at Weeks 14, 22, 30, 38, 46 and 54 in maintenance phase. Participants received vedolizumab in induction phase and achieved clinical response at Week 10 and were randomized to receive placebo in maintenance phase.
Intervention: Vedolizumab (Drug)
Maintenance Phase: Placebo
Vedolizumab placebo-matching, IV infusion, once at Weeks 14, 22, 30, 38, 46 and 54 in maintenance phase. Participants received vedolizumab in induction phase and achieved clinical response at Week 10 and were randomized to receive placebo in maintenance phase.
Intervention: Vedolizumab placebo (Drug)
Maintenance Phase: Vedolizumab 300 mg
Vedolizumab 300 mg, IV infusion, once at Weeks 14, 22, 30, 38, 46 and 54 in maintenance phase. Participants received vedolizumab in induction phase and achieved clinical response at Week 10 and were randomized to receive vedolizumab in maintenance phase.
Intervention: Vedolizumab (Drug)
Maintenance Phase: Placebo continuation
Vedolizumab placebo-matching, IV infusion, once at Weeks 14, 22, 30, 38, 46 and 54 in maintenance phase. Participants received vedolizumab placebo-matching in induction phase and achieved clinical response at Week 10 received placebo in maintenance phase without randomization.
Intervention: Vedolizumab placebo (Drug)
Open-Label Cohort: Vedolizumab 300 mg
Vedolizumab 300 mg, IV infusion, once at Weeks 0, 2 and 6 and then every 8 weeks thereafter up to Week 94 in open-label cohort.
Intervention: Vedolizumab (Drug)
Outcomes
Primary Outcomes
Number of Participants With TEAE Related to Body Weight
Time Frame: From Baseline to 16 weeks after the last dose of study drug (Up to approximately 170 weeks)
Number of Participants Who Experienced at Least One or More Treatment-Emergent Adverse Events (TEAEs)
Time Frame: From Baseline to 16 weeks after the last dose of study drug (Up to approximately 170 weeks)
An Adverse Event (AE) is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (e.g., a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, whether or not it is considered related to the drug. A treatment-emergent adverse event (TEAE) is defined as an adverse event with an onset that occurs after receiving study drug.
Percentage of Participants With a Clinical Response at Week 10 in Induction Phase
Time Frame: Week 10
Clinical response is defined as 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. Mayo Score is a standard assessment tool to measure ulcerative colitis disease activity in clinical trials. The index consists of 4 subscores (rectal bleeding, stool frequency, findings on endoscopy, and physician's global assessment), a global assessment by the physician, and an endoscopic subscore. Each subscore is scored on a scale from 0 to 3 and the complete Mayo score ranges from 0 to 12 (higher scores indicate greater disease activity).
Percentage of Participants With Clinical Remission at Week 60 in Maintenance Phase
Time Frame: Week 60
Clinical Remission is defined as a complete Mayo score of ≤2 points and no individual subscore \>1 point. Mayo Score is a standard assessment tool to measure ulcerative colitis disease activity in clinical trials. The index consists of 4 subscores: rectal bleeding, stool frequency, findings on endoscopy, and physician's global assessment. Each subscore is scored on a scale from 0 to 3 and the complete Mayo score ranges from 0 to 12 (higher scores indicate greater disease activity).
Number of Participants With TEAE Related to Vital Signs
Time Frame: From Baseline to 16 weeks after the last dose of study drug (Up to approximately 170 weeks)
Vital signs included body temperature (axilla), sitting blood pressure (after the participant has rested for at least 5 minutes), and pulse (bpm).
Number of Participants With TEAE Related to Electrocardiogram (ECG)
Time Frame: From Baseline to 16 weeks after the last dose of study drug (Up to approximately 170 weeks)
Number of Participants With Markedly Abnormal Laboratory Parameters Values
Time Frame: From Baseline to 16 weeks after the last dose of study drug (Up to approximately 170 weeks)
The laboratory values outside the range (Hemoglobin \<=7 g/dL, Lymphocytes \<500 /µL, WBC \<2000 /µL, Platelets \<7.5 10\^4/µL, Neutrophils \<1000 /µL, alanine aminotransferase (ALT) \>3.0 U/L x upper limit of normal (ULN), aspartate aminotransferase (AST) \>3.0 U/L x ULN, Total Bilirubin \>2.0 mg/dL x ULN, Amylase \>2.0 (U/L) x ULN were considered markedly abnormal. Only laboratory parameters with events were represented.
Secondary Outcomes
- Percentage of Participants With Mucosal Healing at Week 10 in Induction Phase(Week 10)
- Percentage of Participants With Mucosal Healing at Week 60 in Maintenance Phase(Week 60)
- Percentage of Participants With Durable Remission in Maintenance Phase(Weeks 10 and 60)
- Percentage of Participants With Durable Clinical Response in Maintenance Phase(Weeks 10 and 60)
- Serum Vedolizumab Concentration in Induction Phase(Pre-dose at Weeks 2, 6, 10 and 14)
- Number of Participants With Anti-vedolizumab Antibodies (AVA) in Maintenance Phase(Weeks 0, 10, 30, 60 and 16 weeks after the last dose of study drug (Up to approximately 170 weeks))
- Number of Participants With Neutralizing Anti-vedolizumab Antibodies (AVA) in Induction Phase(Weeks 0, 10 and 16 weeks after the last dose of study drug (Up to approximately 170 weeks))
- Number of Participants With Neutralizing Anti-vedolizumab Antibodies (AVA) in Maintenance Phase(Weeks 0, 10, 30, 60 and 16 weeks after the last dose of study drug (Up to approximately 170 weeks))
- Percentage of Participants With Clinical Remission at Week 10 in Induction Phase(Week 10)
- Serum Vedolizumab Concentration in Maintenance Phase(Pre-dose at Weeks 2, 6, 10, 14, 22, 30 and 60)
- Percentage of Participants With Corticosteroid-Free Remission at Week 60 in Maintenance Phase(Week 60)
- Number of Participants With Anti-vedolizumab Antibodies (AVA) in Induction Phase(Weeks 0, 10 and 16 weeks after the last dose of study drug (Up to approximately 170 weeks))