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

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT02039505
• Date of registration: 16/01/2014
• Prospective Registration: Yes
• Primary sponsor: Takeda
• Public title: Phase III Study of MLN0002 (300 mg) in the Treatment of Ulcerative Colitis
• Scientific 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 Ulcerative Colitis
• Date of first enrolment: February 4, 2014
• Target sample size: 292
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT02039505
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor).
• Phase: Phase 3

Countries of recruitment

Japan

Contacts

• Name: Study Director
• Affiliation: Takeda

Key inclusion & exclusion criteria

Inclusion Criteria:

1. In the opinion of the investigator, a participant is capable of understanding and
complying with protocol requirements.

2. 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.

3. A participant aged 15 to 80 (inclusive) at the time of signing the informed consent
(regardless of sexes).

4. 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.

5. 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.

6. 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.

7. 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.

8. 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.

9. Participants meeting the following treatment failure criteria with at least one of the
following agents within 5 years before signing on the informed consent:

1. 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).

2. Immunomodulators (azathioprine [AZA] or 6- mercaptopurine [6-MP])

- Refractory: Participants whose response was inadequate after treatment for
=12 weeks.

- Intolerance: Participants who were unable to receive continuous treatment
due to adverse reactions (e.g., nausea/vomiting, abdominal pain,
pancreatitis, liver function test abnormalities, lymphopenia, thiopurine
S-methyltransferase genetic mutation, infection).

3. Tumor necrosis factor-alpha (TNFa) antagonist

- Inadequate response: Participants whose response was inadequate after the
induction therapy in the dosage described in the package insert.

- Loss of response: Participants who had recurrence during the scheduled
maintenance therapy after achievement of clinical response (those who
withdrew for other reasons than relapse are not applicable here).

- Intolerance: Participants who were unable to receive continuous treatment
due to adverse reactions (eg, infusion-related reaction, demyelination,
congestive heart failure, infection).

Exclusion Criteria:

1. Participants whose partial Mayo score decrease by 3 points or more between screening
and the start of study drug administration.

2. Participants having or suspected to have abdominal abscess or toxic megacolon.

3. Participants with a history of subtotal or total colectomy.

4. Participants with ileostomy, colostomy, fistula or severe intestinal stenosis.

5. Participants having a treatment history with natalizumab, efalizumab or rituximab.

6. 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.

7. 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.

8. 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.

9. 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.

10. 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.

11. 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).

12. Participants who have received any live-vaccinations within 27 days before the first
dos


Age minimum: 15 Years
Age maximum: 80 Years
Gender: All

Health Condition(s) or Problem(s) studied

Ulcerative Colitis

Intervention(s)

Drug: Vedolizumab placebo

Drug: Vedolizumab

Primary Outcome(s)

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 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)]

Percentage of Participants With Clinical Remission at Week 60 in Maintenance Phase [Time Frame: Week 60]

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)]

Percentage of Participants With a Clinical Response at Week 10 in Induction Phase [Time Frame: Week 10]

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)]

Secondary Outcome(s)

Percentage of Participants With Corticosteroid-Free Remission at Week 60 in Maintenance Phase [Time Frame: Week 60]

Percentage of Participants With Durable Remission in Maintenance Phase [Time Frame: Weeks 10 and 60]

Percentage of Participants With Mucosal Healing at Week 60 in Maintenance Phase [Time Frame: Week 60]

Number of Participants With Anti-vedolizumab Antibodies (AVA) in Induction Phase [Time Frame: 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 [Time Frame: Weeks 0, 10, 30, 60 and 16 weeks after the last dose of study drug (Up to approximately 170 weeks)]

Serum Vedolizumab Concentration in Maintenance Phase [Time Frame: Pre-dose at Weeks 2, 6, 10, 14, 22, 30 and 60]

Serum Vedolizumab Concentration in Induction Phase [Time Frame: Pre-dose at Weeks 2, 6, 10 and 14]

Number of Participants With Anti-vedolizumab Antibodies (AVA) in Maintenance Phase [Time Frame: 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 [Time Frame: Week 10]

Number of Participants With Neutralizing Anti-vedolizumab Antibodies (AVA) in Induction Phase [Time Frame: Weeks 0, 10 and 16 weeks after the last dose of study drug (Up to approximately 170 weeks)]

Percentage of Participants With Durable Clinical Response in Maintenance Phase [Time Frame: Weeks 10 and 60]

Percentage of Participants With Mucosal Healing at Week 10 in Induction Phase [Time Frame: Week 10]

Secondary ID(s)

MLN0002/CCT-101

U1111-1151-6762

JapicCTI-142403

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Results

• Results available: Yes
• Date Posted: 20/03/2019
• URL: https://clinicaltrials.gov/ct2/show/results/NCT02039505