Phase III Study of MLN0002 (300 mg) in the Treatment of Ulcerative Colitis

NCT02039505 | Completed Phase 3 Results FDA Drug

• 3 other identifiers: MLN0002/CCT-101U1111-1151-6762JapicCTI-142403
• Study Type: interventional
• Target: 292
• Locations: 1 country
• Sites: 59

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).

Conditions

Ulcerative Colitis

Keywords

Drug therapy

Outcome Measures

Primary Outcomes (7)

• Percentage of Participants With a Clinical Response at Week 10 in Induction Phase

  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).

  Week 10

• Percentage of Participants With Clinical Remission at Week 60 in Maintenance Phase

  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).

  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 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.

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

• Number of Participants With TEAE Related to Body Weight

  From Baseline 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).

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

• Number of Participants With TEAE Related to Electrocardiogram (ECG)

  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

  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.

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

Secondary Outcomes (12)

• Percentage of Participants With Clinical Remission at Week 10 in Induction Phase

  Week 10

• Percentage of Participants With Mucosal Healing at Week 10 in Induction Phase

  Week 10

• Percentage of Participants With Durable Clinical Response in Maintenance Phase

  Weeks 10 and 60

• 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

Study Arms (7)

Induction Phase: Cohort 1, Placebo

PLACEBO COMPARATOR

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

Drug: Vedolizumab placebo

Induction Phase: Cohort 1, Vedolizumab 300 mg

EXPERIMENTAL

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

Drug: Vedolizumab

Induction Phase: Cohort 2, Vedolizumab 300 mg

EXPERIMENTAL

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

Drug: Vedolizumab

Maintenance Phase: Placebo

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 clinical response at Week 10 and were randomized to receive placebo in maintenance phase.

Drug: Vedolizumab; Drug: Vedolizumab placebo

Maintenance Phase: Vedolizumab 300 mg

EXPERIMENTAL

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.

Drug: Vedolizumab

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 clinical response at Week 10 received placebo in maintenance phase without randomization.

Drug: Vedolizumab placebo

Open-Label Cohort: 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 in open-label cohort.

Drug: Vedolizumab

Interventions

Vedolizumab DRUG

Vedolizumab intravenous infusion

Also known as: MLN0002

Induction Phase: Cohort 1, Vedolizumab 300 mg; Induction Phase: Cohort 2, Vedolizumab 300 mg; Maintenance Phase: Placebo; Maintenance Phase: Vedolizumab 300 mg; Open-Label Cohort: Vedolizumab 300 mg

Vedolizumab placebo DRUG

Vedolizumab placebo

Induction Phase: Cohort 1, 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, 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 ≥2.
• 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
• Resistance: Participants whose response was inadequate after treatment of ≥40 mg/day for ≥1 week (oral or IV) or 30 to 40 mg/day for ≥2 weeks (oral or IV).
• Dependence: Participants for which it is difficult to reduce the dosage to \<10 mg/day due to recurrence during gradual dose reduction (oral or IV).
• Intolerance: Participants who were unable to receive continuous treatment due to adverse reactions (e.g., Cushing's syndrome, osteopenia/osteoporosis, hyperglycaemia, insomnia, infection).
• Immunomodulators (azathioprine \[AZA\] or 6- mercaptopurine \[6-MP\])
• Refractory: Participants whose response was inadequate after treatment for ≥12 weeks.

You may not qualify if:

• 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.
• Participants who have received adalimumab within 27 days before the first dose of the study drug or any biologic agents other than adalimumab within 55 days before the first dose of the study drug. However, this will not apply to participants who have topically received these drugs (eg., intraocular injection for treatment of age-related macular degeneration).
• Participants who have received any live-vaccinations within 27 days before the first dose of the study drug.
• Participants who underwent the enterectomy within 27 days before the first dose of the study drug or those anticipated to require an enterectomy during the study.
• Participants who have received leukocytapheresis or granulocyte apheresis within 27 days before the first dose of the study drug.
• Participants who have been infected with an intestinal pathogen including clostridium difficile or cytomegalovirus within 27 days before the first dose of the study drug.

Sponsors & Collaborators

• Takeda: lead

Study Sites (59)

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Kasugai-shi, Aichi-ken, Japan

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Nagoya, Aichi-ken, Japan

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Toyota-shi, Aichi-ken, Japan

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Hirosaki-shi, Aomori, Japan

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Sakura-shi, Chiba, Japan

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Matsuyama, Ehime, Japan

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Fukui-shi, Fukui, Japan

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Chikushino-shi, Fukuoka, Japan

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Fukuoka, Fukuoka, Japan

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Kitakyushu-shi, Fukuoka, Japan

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Kurume-shi, Fukuoka, Japan

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Fukuyama-shi, Hiroshima, Japan

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Hatsukaichi-shi, Hiroshima, Japan

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Hiroshima, Hiroshima, Japan

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Asahikawa-shi, Hokkaido, Japan

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Hakodate-shi, Hokkaido, Japan

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Sapporo, Hokkaido, Japan

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Tomakomai-shi, Hokkaido, Japan

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Akashi-shi, Hyōgo, Japan

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Himeji-shi, Hyōgo, Japan

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Itami-shi, Hyōgo, Japan

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Kobe, Hyōgo, Japan

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Nishinomiya-shi, Hyōgo, Japan

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Komatsu-shi, Ishikawa-ken, Japan

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Marukame-shi, Kagawa-ken, Japan

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Takamatsu, Kagawa-ken, Japan

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Kagoshima, Kagoshima-ken, Japan

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Fujisawa-shi, Kanagawa, Japan

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Kamakura-shi, Kanagawa, Japan

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Kawasaki-shi, Kanagawa, Japan

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Sagamihara-shi, Kanagawa, Japan

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Yokohama, Kanagawa, Japan

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Kochi, Kochi, Japan

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Kumamoto, Kumamoto, Japan

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Kyoto, Kyoto, Japan

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Sendai, Miyagi, Japan

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Nagasaki, Nagasaki, Japan

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Beppu-shi, Ohita, Japan

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Ōita, Ohita, Japan

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Okayama, Okayama-ken, Japan

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Moriguchi-shi, Osaka, Japan

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Osaka, Osaka, Japan

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Sakai-shi, Osaka, Japan

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Suita-shi, Osaka, Japan

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Saga, Saga-ken, Japan

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Tokorozawa-shi, Saitama, Japan

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Ōtsu, Shiga, Japan

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Hamamatsu, Shizuoka, Japan

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Shimotsuke-shi, 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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Edogawa City, 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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Wakayama, Wakayama, Japan

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Shunan-shi, Yamaguchi, Japan

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Kofu, Yamanashi, Japan

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Related Publications (4)

• Naganuma M, Watanabe K, Motoya S, Ogata H, Matsui T, Suzuki Y, Ursos L, Sakamoto S, Shikamura M, Hori T, Fernandez J, Watanabe M, Hibi T, Kanai T. Potential benefits of immunomodulator use with vedolizumab for maintenance of remission in ulcerative colitis. J Gastroenterol Hepatol. 2022 Jan;37(1):81-88. doi: 10.1111/jgh.15667. Epub 2021 Sep 7.

  PMID: 34409654 DERIVED

• Nagahori M, Watanabe K, Motoya S, Ogata H, Kanai T, Matsui T, Suzuki Y, Pinton P, Ursos L, Sakamoto S, Shikamura M, Hori T, Fernandez J, Hibi T, Watanabe M. Week 2 Symptomatic Response with Vedolizumab as a Predictive Factor in Japanese Anti-TNFalpha-Naive Patients with Ulcerative Colitis: A post hoc Analysis of a Randomized, Placebo-Controlled Phase 3 Trial. Digestion. 2021;102(5):742-752. doi: 10.1159/000512235. Epub 2021 Jan 15.

  PMID: 33454706 DERIVED

• 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

• Motoya S, Watanabe K, Ogata H, Kanai T, Matsui T, Suzuki Y, Shikamura M, Sugiura K, Oda K, Hori T, Araki T, Watanabe M, Hibi T. Vedolizumab in Japanese patients with ulcerative colitis: A Phase 3, randomized, double-blind, placebo-controlled study. PLoS One. 2019 Feb 26;14(2):e0212989. doi: 10.1371/journal.pone.0212989. eCollection 2019.

  PMID: 30807613 DERIVED

MeSH Terms

Conditions

Colitis, Ulcerative

Interventions

vedolizumab

Condition Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Medical Director
• Organization: Takeda

trialdisclosures@takeda.com

+1-877-825-3327

Study Officials

• Study Director

  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 16, 2014
• First Posted: January 17, 2014
• Study Start: February 4, 2014
• Primary Completion: February 27, 2018
• Study Completion: June 28, 2018
• Last Updated: April 25, 2019
• Results First Posted: March 20, 2019

Record last verified: 2019-04

Data Sharing

• IPD Sharing: Will share

Locations

JP (59)