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

NCT02038920 | Completed Phase 3 Results FDA Drug

• 3 other identifiers: MLN0002/CCT-001U1111-1150-2688JapicCTI-142402
• Study Type: interventional
• Target: 157
• Locations: 1 country
• Sites: 56

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.

Conditions

Crohn's Disease

Keywords

Drug Therapy

Outcome Measures

Primary Outcomes (7)

• Induction Phase: Percentage of Participants With Crohn's Disease Activity Index (CDAI)-100 Response

  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.

  Week 10

• Maintenance Phase: Percentage of Participants With Clinical Remission

  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.

  Week 60

• Number of Participants Who Experienced at Least One or More Treatment-Emergent Adverse Events (TEAEs)

  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.

  From Baseline up to 16 weeks after the last dose of study drug (Up to approximately 170 weeks)

• Number of Participants With TEAE Related to Body Weight (Weight Decreased)

  Reported events on this outcome measure were "Weight Decreased".

  From Baseline up to 16 weeks after the last dose of study drug (Up to approximately 170 weeks)

• Number of Participants With TEAE Related to Vital Signs

  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".

  From Baseline up to 16 weeks after the last dose of study drug (Up to approximately 170 weeks)

• Number of Participants With TEAE Related to Electrocardiogram (ECG) [Bundle Branch Block Right]

  Reported events on this outcome measure were "Bundle Branch Block Right".

  From Baseline up to 16 weeks after the last dose of study drug (Up to approximately 170 weeks)

• Number of Participants With Markedly Abnormal Values of Laboratory Parameters Values

  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.

  From Baseline up to 16 weeks after the last dose of study drug (Up to approximately 170 weeks)

Secondary Outcomes (13)

• 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 Crohn's Disease Activity Index (CDAI)-100 Response

  Week 60

• Maintenance Phase: Percentage of Participants With Durable Clinical Remission

  From Week 14 and Week 60

• Maintenance Phase: Percentage of Participants With Corticosteroid-free Clinical Remission

  Week 60

Study Arms (6)

Induction Phase: Vedolizumab, 300 mg

EXPERIMENTAL

Vedolizumab 300 mg, intravenous (IV) infusion, once at Weeks 0, 2 and 6 in the induction phase.

Drug: Vedolizumab

Induction Phase: Placebo

PLACEBO COMPARATOR

Vedolizumab placebo-matching IV infusion once at Weeks 0, 2 and 6 in the induction phase.

Drug: Vedolizumab placebo

Maintenance Phase: Vedolizumab 300 mg

EXPERIMENTAL

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.

Drug: Vedolizumab

Maintenance Phase: Placebo

PLACEBO COMPARATOR

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.

Drug: Vedolizumab placebo

Maintenance Phase: Placebo Continuation

PLACEBO COMPARATOR

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.

Drug: Vedolizumab placebo

Open-Label: Vedolizumab 300 mg

EXPERIMENTAL

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.

Drug: Vedolizumab

Interventions

Vedolizumab DRUG

Vedolizumab IV injection

Also known as: MLN0002

Induction Phase: Vedolizumab, 300 mg; Maintenance Phase: Vedolizumab 300 mg; Open-Label: Vedolizumab 300 mg

Vedolizumab placebo DRUG

Vedolizumab placebo-matching IV infusion

Induction Phase: Placebo; Maintenance Phase: Placebo; Maintenance Phase: Placebo Continuation

Eligibility Criteria

• Age: 15 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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)
• 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
• Corticosteroids
• Resistance
• Dependence

You may not qualify if:

• 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
• Participants who had received any live vaccinations within 27 days before initiation of study drug administration
• Participants who had undergone intestinal resection within 27 days before initiation of study drug administration or those anticipated to require intestinal resection during the study
• Participants who had received leukocytapheresis or granulocyte apheresis within 27 days before initiation of the study drug administration
• Participants who had received intravenous hyperalimentation or total enteral nutrition within the 20 days before initiation of the study drug administration or participants who are fasted
• Participants who had 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

Sponsors & Collaborators

• Takeda: lead

Study Sites (56)

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Nagoya, Aichi-ken, Japan

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Toyota, Aichi-ken, Japan

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Hirosaki, Aomori, Japan

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Abiko, Chiba, Japan

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Kashiwa, Chiba, Japan

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Sakura, Chiba, Japan

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Matsuyama, Ehime, Japan

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Chikushino-shi, Fukuoka, Japan

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Kasuga, Fukuoka, Japan

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Kitakyushu, Fukuoka, Japan

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Takasaki, Gunma, Japan

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Fukuyama, Hiroshima, Japan

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Hatsukaichi, Hiroshima, Japan

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Asahikawa, Hokkaido, Japan

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Sapporo, Hokkaido, Japan

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Tomakomai, Hokkaido, Japan

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Akashi, Hyōgo, Japan

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Nishinomiya, Hyōgo, Japan

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Takamatsu, Kagawa-ken, Japan

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Kamakura, Kanagawa, Japan

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Kawasaki, Kanagawa, Japan

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Sagamihara, Kanagawa, Japan

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Yokohama, Kanagawa, Japan

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Kochi, Kochi, Japan

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Sendai, Miyagi, Japan

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Kurashiki, Okayama-ken, Japan

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Moriguchi, Osaka, Japan

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Suita, Osaka, Japan

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Tokorozawa, Saitama, Japan

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Ōtsu, Shiga, Japan

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Hamamatsu, Shizuoka, Japan

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Shimotsuke, Tochigi, Japan

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Adachi-ku, Tokyo, Japan

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Bunkyo-ku, Tokyo, Japan

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Chiyoda-ku, Tokyo, Japan

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Minato-ku, Tokyo, Japan

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Shinagawa-ku, Tokyo, Japan

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Shinjuku-ku, Tokyo, Japan

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Shūnan, Yamaguchi, Japan

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Kofu, Yamanashi, Japan

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Chiba, Japan

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Fukui, Japan

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Fukuoka, Japan

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Hiroshima, Japan

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Kagoshima, Japan

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Kumamoto, Japan

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Kyoto, Japan

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Nagasaki, Japan

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Niigata, Japan

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Okayama, Japan

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Okinawa, Japan

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Osaka, Japan

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Ōita, Japan

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Saga, Japan

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Saitama, Japan

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Wakayama, Japan

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Related Publications (1)

• Okamoto H, Dirks NL, Rosario M, Hori T, Hibi T. Population pharmacokinetics of vedolizumab in Asian and non-Asian patients with ulcerative colitis and Crohn's disease. Intest Res. 2021 Jan;19(1):95-105. doi: 10.5217/ir.2019.09167. Epub 2020 Jul 10.

  PMID: 32635680 DERIVED

MeSH Terms

Conditions

Crohn Disease

Interventions

vedolizumab

Condition Hierarchy (Ancestors)

Inflammatory Bowel Diseases; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Intestinal Diseases

Results Point of Contact

• Title: Medical Director
• Organization: Takeda

trialdisclosures@takeda.com

877-825-3327

Study Officials

• Study Director Clinical Science

  Takeda

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 15, 2014
• First Posted: January 17, 2014
• Study Start: January 28, 2014
• Primary Completion: January 25, 2019
• Study Completion: May 21, 2019
• Last Updated: December 9, 2019
• Results First Posted: December 9, 2019

Record last verified: 2019-11

Data Sharing

• IPD Sharing: Will share

Locations

JP (56)