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Phase III Study of MLN0002 (300 mg) in Treatment of Crohn's Disease

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ClinicalTrials.gov Identifier: NCT02038920
Recruitment Status : Completed
First Posted : January 17, 2014
Last Update Posted : June 12, 2019
Sponsor:
Information provided by (Responsible Party):
Takeda

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 MLN0002 (Vedolizumab) in induction and maintenance therapy in Japanese patients with moderately or severely active Crohn's disease.

Condition or disease Intervention/treatment Phase
Crohn's Disease Drug: Vedolizumab Drug: Vedolizumab placebo Phase 3

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 patients with moderately or severely active Crohn's disease.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 157 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: 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
Actual Study Start Date : January 28, 2014
Actual Primary Completion Date : January 25, 2019
Actual Study Completion Date : May 21, 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Crohn's Disease
Drug Information available for: Vedolizumab

Arm Intervention/treatment
Experimental: Vedolizumab 300mg
Intravenous Vedolizumab (300 mg) administered at Weeks 0, 2, and 6 and every 8 weeks thereafter
Drug: Vedolizumab
Vedolizumab intravenous injection
Other Name: MLN0002

Placebo Comparator: Placebo
Vedolizumab Placebo. Intravenous infusion at Weeks 0, 2, and 6 and every 8 weeks thereafter
Drug: Vedolizumab placebo
Vedolizumab placebo




Primary Outcome Measures :
  1. Induction phase: Crohn's Disease Activity Index (CDAI)-100 Response at Week 10 [ Time Frame: At Week 10 ]
    Reported data will be percentage of subjects randomized to the induction phase with 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. Index values of 150 and below are associated with quiescent disease; values above that indicate active disease.

  2. Maintenance Phase: Clinical Remission at Week 60 [ Time Frame: At Week 60 ]
    Reported data will be percentage of subjects randomized to the maintenance phase with clinical remission (CDAI score ≤150) at Week 60. 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.

  3. 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 ]
    Tabulation of incidence of adverse events 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 treatment-emergent adverse event (TEAE) is defined as an adverse event with an onset that occurs after receiving study drug.

  4. Number of Participants with TEAE Related to Body Weight [ Time Frame: From baseline to 16 weeks after the last dose of study drug ]
  5. Number of Participants with TEAE Related to Vital Signs [ Time Frame: From baseline to 16 weeks after the last dose of study drug ]
    Vital signs include body temperature (axilla), sitting blood pressure (after the participant has rested for at least 5 minutes), and pulse (bpm).

  6. Number of Participants with TEAE Related to Electrocardiogram (ECG) [ Time Frame: From baseline to 16 weeks after the last dose of study drug ]
  7. Number of Participants with Markedly Abnormal Values of Laboratory Parameters Values [ Time Frame: From baseline to 16 weeks after the last dose of study drug ]
    The laboratory values outside the range (Hemoglobin <=7 g/dL, Lymphocytes <500 /microL, WBC <2000 /microL, Platelets <7.5 10^4/microL, Neutrophils <1000 /microL, ALT (GPT) >3.0 U/L x upper limit of normal (ULN), AST (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.


Secondary Outcome Measures :
  1. Induction phase: Clinical Remission at Week 10 [ Time Frame: At Week 10 ]
    Reported data will be percentage of subjects randomized to the induction phase with clinical remission (CDAI score ≤150) at Week 10. 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.

  2. Induction phase: Changes in C-reactive Protein (CRP) Values [ Time Frame: From baseline to Week 10 ]
    Summary statistics of C-reactive protein (CRP) values at each evaluation time point in the subpopulation of subjects randomized to the induction phase with a baseline CRP value exceeding 0.30 mg/dL

  3. Maintenance Phase: CDAI-100 Response at Week 60 [ Time Frame: At Week 60 ]
    Reported data will be percentage of subjects randomized to the maintenance phase with a decrease from baseline of at least 100 points in the CDAI score at Week 60. 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.

  4. Maintenance Phase: Durable Clinical Remission [ Time Frame: From Week 14 to Week 60 ]
    Reported data will be percentage of subjects randomized to the maintenance phase with clinical remission (CDAI score ≤ 150) at least 80 percent of the scheduled visits, including Week 60. 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.

  5. Maintenance Phase: Corticosteroid-free Clinical Remission at Week 60 [ Time Frame: At Week 60 ]
    Reported data will be percentage of subjects randomized to the maintenance phase who are not using the corticosteroids used at initiation of study drug administration and who show clinical remission (CDAI score ≤ 150) at Week 60. 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.

  6. Serum Vedolizumab Concentration [ Time Frame: From Week 2 to Week 60 ]
    Summary statistics for serum Vedolizumab concentration at each evaluation time point

  7. Human Anti-human Antibody (HAHA) [ Time Frame: From baseline to 16 weeks after the last dose of study drug ]
    Tabulation of incidence of Human anti-human antibody (HAHA)

  8. Neutralizing Antibody [ Time Frame: From baseline to 16 weeks after the last dose of study drug ]
    Tabulation of incidence of neutralizing antibody



Information from the National Library of Medicine

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Ages Eligible for Study:   15 Years to 80 Years   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Participants aged 15 to 80 years (inclusive) at the time of consent
  2. Participants with a diagnosis of small-intestinal, large-intestinal, or small-/large-intestinal Crohn's disease 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
  3. Participants with baseline Crohn's Disease Activity Index (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
  4. In case of the participants who meet any of the following criteria; participants with ≥ 8-year history of extensive or limited colitis, participants aged ≥ 50 years, or participants with a first-degree family history of colon cancer, those whom the complication of colon cancer or dysplasia was ruled out by total colonoscopy at the start of study drug administration (Or the results from total colonoscopy performed within 1 year before giving consent are available)
  5. Participants meeting the criteria for treatment failure below with at least one of the following agents received within previous 5 year period before giving consent

    1. Corticosteroids

      • Resistance
      • Dependence
      • Intolerance
    2. Immunomodulators (azathioprine, 6-mercaptopurine or methotrexate)

      • Refractory
      • Intolerance
    3. Anti-TNFα antibodies

      • Inadequate response
      • Loss of response
      • Intolerance

Exclusion Criteria:

  1. Participants with an evidence of or suspected abdominal abscess
  2. Participants with a history of subtotal or total colectomy
  3. Participants who have had a resection of the small intestine in at least 3 locations or have a diagnosis of short bowel syndrome
  4. Participants with ileostomy, colostomy, or internal fistula, or severe intestinal stenosis
  5. 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
  6. Participants who have 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
  7. Participants who have 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
  8. Participants who have received cyclosporin, tacrolimus, tofacitinib or any study drugs for treatment of ulcerative colitis within 27 days before initiation of the study drug administration
  9. Participants who have 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
  10. Participants who have received any live vaccinations within 27 days before initiation of study drug administration
  11. Participants who have undergone intestinal resection within 27 days before initiation of study drug administration or those anticipated to require intestinal resection during the study
  12. Participants who have received leukocytapheresis or granulocyte apheresis within 27 days before initiation of the study drug administration
  13. Participants who have received intravenous hyperalimentation or total enteral nutrition within the 20 days before initiation of the study drug administration. Or participants who are fasted
  14. Participants who have received enteral nutrition at > 900 kcal/day or started enteral nutrition at <= 900 kcal/day within the 20 days before initiation of the study drug administration. Participants receiving 900 kcal/day or less of enteral nutrition for at least 21 days before initiation of the study drug administration whom these dosage was changed or the medications were discontinued within 20 days before initiation of the study drug administration
  15. Participants with evidence of adenomatous colonic polyps that need to be removed at the start of study drug administration
  16. Participants with a history or an complication of dysplasia of the small or large intestine

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02038920


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Sponsors and Collaborators
Takeda
Investigators
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Study Director: Study Director Takeda

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Responsible Party: Takeda
ClinicalTrials.gov Identifier: NCT02038920     History of Changes
Other Study ID Numbers: MLN0002/CCT-001
U1111-1150-2688 ( Other Identifier: WHO )
JapicCTI-142402 ( Registry Identifier: JapicCTI )
First Posted: January 17, 2014    Key Record Dates
Last Update Posted: June 12, 2019
Last Verified: June 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Takeda makes patient-level, de-identified data sets and associated documents available for all interventional studies after applicable marketing approvals and commercial availability have been received (or program is completely terminated), an opportunity for the primary publication of the research and final report development has been allowed, and other criteria have been met as set forth in Takeda's Data Sharing Policy (see www.TakedaClinicalTrials.com for details). To obtain access, researchers must submit a legitimate academic research proposal for adjudication by an independent review panel, who will review the scientific merit of the research and the requestor's qualifications and conflict of interest that can result in potential bias. Once approved, qualified researchers who sign a data sharing agreement are provided access to these data in a secure research environment.

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes
Keywords provided by Takeda:
Drug Therapy
Additional relevant MeSH terms:
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Crohn Disease
Inflammatory Bowel Diseases
Gastroenteritis
Gastrointestinal Diseases
Digestive System Diseases
Intestinal Diseases
Vedolizumab
Gastrointestinal Agents