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 Crohn's Disease
Overview
- Phase
- Phase 3
- Intervention
- Vedolizumab
- Conditions
- Crohn's Disease
- Sponsor
- Takeda
- Enrollment
- 157
- Primary Endpoint
- Number of Participants With TEAE Related to Electrocardiogram (ECG) [Bundle Branch Block Right]
- Status
- Completed
- Last Updated
- 6 years ago
Overview
Brief Summary
This study is a phase 3, multicenter, randomized, double-blinded, placebo-controlled, parallel-group study to examine the efficacy, safety, and pharmacokinetics of vedolizumab (MLN0002) in induction and maintenance therapy in Japanese participants with moderately or severely active Crohn's disease.
Detailed Description
This is a phase 3, multicenter, randomized, double-blinded, placebo-controlled, parallel-group study to examine the efficacy, safety, and pharmacokinetics of intravenous vedolizumab (300 mg) infusion in induction and maintenance therapy in Japanese participants with moderately or severely active Crohn's disease.
Investigators
Eligibility Criteria
Inclusion Criteria
- •In the opinion of the investigator, participants were capable of understanding and complying with protocol requirements
- •Participants or, when applicable, participants legally acceptable representative sign and date the informed consent form prior to initiation of any study procedures
- •Participants aged 15 to 80 years (inclusive) at the time of consent
- •A nonsterilized male participant who has a female partner of child-bearing potential has to agree to use adequate contraception during the period from the signing of informed consent to 6 months after the last dose of the study drug
- •A female participant of child-bearing potential (i.e., nonsterilized or whose last regular menses was within previous 2 years) who has a nonsterilized male partner has to agree to use adequate contraception during the period from the signing of informed consent to 6 months after the last dose of the study drug
- •Participants with a diagnosis of small-intestinal, large-intestinal, or small-/large-intestinal Crohn's disease (CD) established based on the Revised Diagnostic Criteria for Crohn's disease issued by Research Group for Intractable Inflammatory Bowel Disease Designated as Specified Disease by the Ministry of Health, Labor and Welfare of Japan (2012) at least 3 months before the start of administration of study drug
- •Participants with baseline CDAI score of 220 to 450(inclusive) and meeting at least one of the followings:
- •C-reactive protein (CRP) at screening test is above 0.30 mg/dL
- •Participants with irregular or semicircular ulcers or multiple aphthae (10 or more) observed over an extensive area of the small or large intestine on endoscopy or imaging test within the 4 months before the start of administration of study drugs
- •Participants with longitudinal ulcers or a cobblestone appearance observed in the small or large intestine on endoscopy or imaging test within 4 months before the start of administration of study drugs
Exclusion Criteria
- •Participants with an evidence of or suspected abdominal abscess
- •Participants with a history of subtotal or total colectomy
- •Participants who have had a resection of the small intestine in at least 3 locations or have a diagnosis of short bowel syndrome
- •Participants with ileostomy, colostomy, or internal fistula, or severe intestinal stenosis
- •Participants who have a treatment history with natalizumab, efalizumab or rituximab
- •Participants who started 5-aminosalicylic acid oral drug or probiotics treatment, antimicrobials to treat Crohn's disease, or 30 mg/day or less of oral corticosteroids within 13 days before initiation of study drug administration. If these drugs were used within 14 days before initiation of study drug administration, the dosage must have been changed or their use discontinued within 13 days before the initiation of study drug administration
- •Participants who had received 5-aminosalicylic acid or corticosteroid enemas/suppositories, intravenous corticosteroid injections, or more than 30 mg/day of oral corticosteroids, medications for diarrhea-predominant irritable bowel syndrome, or Chinese herbal medicine for the treatment of Crohn's disease (e.g., Daikenchuto) within 13 days before initiation of study drug administration
- •Participants who had received azathioprine, 6-mercaptopurine, or methotrexate within 27 days before initiation of study drug administration. However, this shall not apply to participants who have received these drugs for 83 or more days before initiation of the study drug administration and continued the steady dose administration of the drugs for 27 or more days before initiation of the study drug administration
- •Participants who had received cyclosporin, tacrolimus, tofacitinib or any study drugs for treatment of ulcerative colitis within 27 days before initiation of the study drug administration
- •Participants who had received adalimumab within 27 days before initiation of study drug administration or any biological drugs other than adalimumab within 55 days before initiation of study drug administration. Topical administration (such as intraocular implantation for treatment of age-related maculopacy) is allowed
Arms & Interventions
Induction Phase: Vedolizumab, 300 mg
Vedolizumab 300 mg, intravenous (IV) infusion, once at Weeks 0, 2 and 6 in the induction phase.
Intervention: Vedolizumab
Induction Phase: Placebo
Vedolizumab placebo-matching IV infusion once at Weeks 0, 2 and 6 in the induction phase.
Intervention: Vedolizumab placebo
Maintenance Phase: Vedolizumab 300 mg
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 Crohn's Disease Activity Index (CDAI)-70 response at Week 10 and were randomized to receive vedolizumab in maintenance phase.
Intervention: Vedolizumab
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 CDAI-70 response at Week 10 and were randomized to receive placebo in maintenance phase.
Intervention: Vedolizumab placebo
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 CDAI-70 response at Week 10 received placebo in maintenance phase without randomization.
Intervention: Vedolizumab placebo
Open-Label: 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 as a maximum duration in open-label phase.
Intervention: Vedolizumab
Outcomes
Primary Outcomes
Number of Participants With TEAE Related to Electrocardiogram (ECG) [Bundle Branch Block Right]
Time Frame: From Baseline up to 16 weeks after the last dose of study drug (Up to approximately 170 weeks)
Reported events on this outcome measure were "Bundle Branch Block Right".
Maintenance Phase: Percentage of Participants With Clinical Remission
Time Frame: Week 60
Clinical remission is defined as the CDAI score ≤150. CDAI is scoring system for the assessment of Crohn's disease activity. Index values of 150 and below are associated with quiescent disease; values above that indicate active disease.
Number of Participants With Markedly Abnormal Values of Laboratory Parameters Values
Time Frame: From Baseline up 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 /microL, White Blood Cell (WBC) \<2000 /microL, Platelets \<7.5 10\^4/microL, Neutrophils \<1000 /microL, Alanine Aminotransferase (ALT) (Glutamic Pyruvic Transaminase; GPT) \>3.0 U/L x upper limit of normal (ULN), Aspartate Aminotransferase (AST) (Glutamic Oxaloacetic Transaminase; GOT) \>3.0 U/L x ULN, Total Bilirubin \>2.0 mg/dL x ULN, Amylase \>2.0 (U/L) x ULN are considered markedly abnormal.
Number of Participants Who Experienced at Least One or More Treatment-Emergent Adverse Events (TEAEs)
Time Frame: From Baseline up 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 study participant who received a drug (including a study 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 TEAE is defined as an adverse event with an onset that occurs after receiving study drug.
Number of Participants With TEAE Related to Body Weight (Weight Decreased)
Time Frame: From Baseline up to 16 weeks after the last dose of study drug (Up to approximately 170 weeks)
Reported events on this outcome measure were "Weight Decreased".
Induction Phase: Percentage of Participants With Crohn's Disease Activity Index (CDAI)-100 Response
Time Frame: Week 10
A response to therapy is considered a decrease from baseline of at least 100 points in the CDAI score at Week 10. CDAI is scoring system for the assessment of Crohn's disease activity. The total CDAI score ranges from 0 to approximately 600, where higher scores indicate more severe disease. Index values of 150 and below are associated with quiescent disease; values above that indicate active disease.
Number of Participants With TEAE Related to Vital Signs
Time Frame: From Baseline up 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). Reported events on this outcome measure were "Pyrexia", "Body temperature increased", "Hypertension", and "Orthostatic hypotension".
Secondary Outcomes
- Serum Vedolizumab Concentration in Induction Phase(Weeks 2, 6, 10 and 14)
- Induction Phase: Percentage of Participants With Clinical Remission(Week 10)
- Induction Phase: Change From Baseline in C-reactive Protein (CRP) Values(Baseline to Week 10)
- Maintenance Phase: Percentage of Participants With Corticosteroid-free Clinical Remission(Week 60)
- 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 in maintenance phase)
- Number of Participants With Anti-vedolizumab Antibodies (AVA) in Open Label Cohort(Weeks 0, 10, 30, 62, 94 and 16 weeks after the last dose of study drug in open-label cohort)
- Maintenance Phase: Percentage of Participants With Durable Clinical Remission(From Week 14 and 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 in induction phase)
- 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 in induction phase)
- Maintenance Phase: Percentage of Participants With Crohn's Disease Activity Index (CDAI)-100 Response(Week 60)
- 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 in maintenance phase)
- Number of Participants With Neutralizing Anti-vedolizumab Antibodies (AVA) in Open Label Cohort(Weeks 0, 10, 30, 62, 94 and 16 weeks after the last dose of study drug in open-label cohort)
- Serum Vedolizumab Concentration in Maintenance Phase(Weeks 2, 6, 10, 14, 22, 30 and 60)