Long-term Safety With Vedolizumab Intravenous (IV) in Pediatric Participants With Ulcerative Colitis (UC) or Crohn's Disease (CD)

• ClinicalTrials.gov Identifier: NCT03196427
• Recruitment Status: Active, not recruiting
• First Posted: June 22, 2017
• Last Update Posted: January 8, 2021
• Sponsor: Takeda
• Collaborators: Takeda Development Center Americas, Inc.; Takeda Development Centre Europe Ltd.
• Information provided by (Responsible Party): Takeda

Tracking Information

• First Submitted Date: June 20, 2017
• First Posted Date: June 22, 2017
• Last Update Posted Date: January 8, 2021
• Actual Study Start Date: July 30, 2018
• Estimated Primary Completion Date: May 25, 2025 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: March 13, 2018)

Percentage of Participants with Treatment-emergent Adverse Events (TEAEs) [ Time Frame: Baseline up to 5 years ]

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 (example, 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.

Original Primary Outcome Measures (submitted: June 20, 2017)

Percentage of Participants with Treatment-emergent Adverse Events (TEAEs) [ Time Frame: Baseline up to 5 years ]

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 (eg, 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.

Current Secondary Outcome Measures (submitted: March 13, 2018)

• Time to Major Inflammatory Bowel Disease (IBD) - Related Events [ Time Frame: Baseline up to 5 years ]
  Major IBD-related events included hospitalizations, surgeries, or procedures due to UC and CD.
• Change from Baseline in IMPACT-III Total and Subscale Scores at Week 24 and Every 24 weeks, Thereafter up to 5 years [ Time Frame: Baseline up to 5 years ]
  The IMPACT-III questionnaire is a self-reported measure with 35 closed questions encompassing 6 domains: Bowel Symptoms (7 items), Systemic Symptoms (3 items), Social Functioning (12 items), Body Image (3 items), Treatment/Interventions (3 items), and Emotional Functioning (7 items). The IMPACT-III uses a 5-point Likert scale ranging from 1 to 5 for all answers. The outcome score ranges from 35 to 175, with higher scores suggesting better quality of life.
• Height Velocity at Week 48 and Every 48 weeks, Thereafter up to 5 years [ Time Frame: Baseline up to 5 years ]
  Height velocity (cm/year) is the change in height per year.
• Change from Baseline in Height at Week 24 and Every 24 Weeks, Thereafter up to 5 years [ Time Frame: Baseline up to 5 years ]
• Change from Baseline in Weight at Week 24 and Every 24 Weeks, Thereafter up to 5 years [ Time Frame: Baseline up to 5 years ]
• Change from Baseline in Body Mass Index (BMI) at Week 24 and Every 24 Weeks, Thereafter up to 5 years [ Time Frame: Baseline up to 5 years ]
  BMI = Weight (in kilograms)/height^2 (in meters).
• Percentage of Participants Achieving Tanner Stage V Scale [ Time Frame: Baseline up to 5 years ]
  Tanner Stage Evaluation is a scale used to evaluate growth parameters standardized for age, sex, and pubertal development. Female pubertal development staged by pubic hair development and breast size; male pubertal development staged by size of the genitalia and development of pubic hair. Rated in 5 stages: stage 1 (no development) to 5 (adult-like development in quantity and size). Tanner stage is assessed at or before age 16 years for females or 17 years for males.
• Percentage of Participants With UC Meeting Complete Mayo Score Response at Week 32 [ Time Frame: Week 32 ]
  Clinical response is defined as a continued reduction in complete mayo score of >=3 points from baseline (at initiation of MLN0002-2003) and continued decrease in rectal bleeding subscore of >=1 point from baseline, or absolute rectal bleeding subscore of <=1 point. Mayo score is an instrument designed to measure disease activity of UC. It consists of 4 subscores: stool frequency, rectal bleeding, findings on endoscopy and physician rating of disease activity, each graded from 0 to 3 with higher scores indicating more severe disease. These scores are summed to give a total score range of 0 to 12; where higher scores indicate more severe disease.
• Percentage of Participants With CD Meeting 50 Percent (%) Reduction in Simple Endoscopic Score for Crohn's Disease (SES-CD) Score at Week 32 [ Time Frame: Week 32 ]
  Clinical response is defined as a 50% reduction in SES-CD score on endoscopy compared to the baseline endoscopy (at initiation of MLN0002-2003) and continued reduction in CDAI that is a >=70 point decrease from the baseline Crohn's disease activity index (CDAI) score at the initiation of MLN0002-2003. CDAI is a research tool used to quantify the symptoms of participants with Crohn's disease. SES-CD consists of 3 variables: ulcer size, ulcerated and affected surfaces and presence of narrowing each graded from 0 to 3 with score of 0 means no colonic lesions or mucosal healing, and SES-CD greater than (>) 1 indicates the presence of mucosal lesions.

Original Secondary Outcome Measures (submitted: June 20, 2017)

• Time to Major Inflammatory Bowel Disease (IBD) - Related Events [ Time Frame: Baseline up to 5 years ]
  Major IBD-related events included hospitalizations, surgeries, or procedures due to ulcerative colitis (UC) and Crohn's disease (CD).
• Change from Baseline in IMPACT-III Total and Subscale Scores at Week 24 and Every 24 weeks, Thereafter up to 5 years [ Time Frame: Baseline up to 5 years ]
  The IMPACT-III questionnaire is a self-reported measure with 35 closed questions encompassing 6 domains: Bowel Symptoms (7 items), Systemic Symptoms (3 items), Social Functioning (12 items), Body Image (3 items), Treatment/Interventions (3 items), and Emotional Functioning (7 items). The IMPACT-III uses a 5-point Likert scale ranging from 1 to 5 for all answers. The outcome score ranges from 35 to 175, with higher scores suggesting better quality of life.
• Height Velocity at Week 48 and Every 48 weeks, Thereafter up to 5 years [ Time Frame: Baseline up to 5 years ]
  Height velocity (cm/year) is the change in height per year.
• Change from Baseline in Height at Week 24 and Every 24 Weeks, Thereafter up to 5 years [ Time Frame: Baseline up to 5 years ]
• Change from Baseline in Weight at Week 24 and Every 24 Weeks, Thereafter up to 5 years [ Time Frame: Baseline up to 5 years ]
• Change from Baseline in Body Mass Index (BMI) at Week 24 and Every 24 Weeks, Thereafter up to 5 years [ Time Frame: Baseline up to 5 years ]
  BMI = Weight (in kilograms)/height^2 (in meters).
• Percentage of Participants Achieving Tanner Stage V Scale [ Time Frame: Baseline up to 5 years ]
  Tanner Stage Evaluation is a scale used to evaluate growth parameters standardized for age, sex, and pubertal development. Female pubertal development staged by pubic hair development and breast size; male pubertal development staged by size of the genitalia and development of pubic hair. Rated in 5 stages: stage 1 (no development) to 5 (adult-like development in quantity and size). Tanner stage is assessed at or before age 16 years for females or 17 years for males.

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Long-term Safety With Vedolizumab Intravenous (IV) in Pediatric Participants With Ulcerative Colitis (UC) or Crohn's Disease (CD)
• Official Title: A Phase 2b, Extension Study to Determine the Long-term Safety of Vedolizumab IV in Pediatric Subjects With Ulcerative Colitis or Crohn's Disease
• Brief Summary: The purpose of this study is to determine the safety profile of long-term vedolizumab IV treatment in pediatric participants with UC or CD.

Detailed Description

The drug being tested in this study is called Vedolizumab. Vedolizumab is being tested to treat pediatric participants who have moderately to severely active UC or CD.

This study will look at the long-term safety profile in participants who take vedolizumab IV. Participants will be randomly assigned (by chance, like flipping a coin) which will remain undisclosed to the participant and investigator during this double blind study (up to Week 40) maintaining the dose at study entry and escalating the dose at disease worsening.

The dosing regimen selected for the long-term study is intended to maintain clinical response at the lowest possible exposure.

At the discretion of the investigator, participants receiving the low dose (150 or 100 mg) of vedolizumab IV may be escalated to the high dose (300 or 200 mg) if the participants demonstrate disease worsening at 2 consecutive visits (scheduled or unscheduled).

Participants who experience continued disease worsening during the study despite being administered vedolizumab 300 or 200 mg every 8 weeks (Q8W) will be discontinued from the study.

Study duration is expected to be up to 5 years, depending on the enrollment rate in the previous randomized double blind study (MLN0002-2003).

• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Treatment

Condition

• Ulcerative Colitis
• Crohn's Disease

Intervention

Drug: Vedolizumab

Vedolizumab intravenous infusion.

Other Names:

• MLN0002
• ENTYVIO
• KYNTELES

Study Arms

• Experimental: Vedolizumab High Dose Group
  Participants with UC or CD having baseline weight of greater than or equal to (>=) 30 kilogram (kg) will receive Vedolizumab 300 milligram (mg) and participants with UC or CD having baseline weight of less than (<) 30 kg will receive Vedolizumab 200 mg, intravenous infusion, every 8 weeks for up to 5 years.
  Intervention: Drug: Vedolizumab
• Experimental: Vedolizumab Low Dose Group
  Participants with UC or CD having baseline weight of >= 30 kg will receive Vedolizumab 150 mg and participants with UC or CD having baseline weight of < 30 kg will receive Vedolizumab 100 mg intravenous infusion, every 8 weeks for up to 5 years.
  Intervention: Drug: Vedolizumab

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Active, not recruiting
• Estimated Enrollment (submitted: June 20, 2017): 80
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: May 25, 2025
• Estimated Primary Completion Date: May 25, 2025 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

1. Is male or female with Ulcerative Colitis or Crohn's Disease and was between 2 to 17 years, inclusive, at the time of randomization for Study MLN0002-2003.

   (Note: A participant remains eligible to participate in this study after they reach 18 years of age if they continue to meet the inclusion criteria and do not meet any exclusion criteria.)

2. Has completed Study MLN0002-2003 and, at Week 22, achieved clinical response as defined by a reduction of partial Mayo score of >= 2 points and >= 25% from Baseline, or a reduction of the paediatric ulcerative colitis activity index (PUCAI) of >= 20 points from baseline for participants with UC; or a reduction of the CDAI as defined by a >= 70-point decrease from Baseline or a decrease of pediatric crohn's disease activity index (PCDAI) of >= 15 points for participants with CD.

3. May be receiving a therapeutic dose of the following drugs:

   • Oral 5-aminosalicylic acid (5-ASA) compounds.
   • Oral corticosteroid therapy (prednisone or equivalent steroid at a dose less than or equal to [<=] 50 milligram per day [mg/day], budesonide at a dose <= 9 mg/day).
   • Topical (rectal) treatment with 5-ASAs or corticosteroids.
   • Probiotics (example, Saccharomyces boulardii).
   • Antidiarrheals (example, loperamide, diphenoxylate with atropine) for control of chronic diarrhea.
   • Antibiotics used for the treatment of CD (i.e., ciprofloxacin, metronidazole).
   • Azathioprine (AZA) or 6-mercaptopurine (6-MP) or methotrexate (MTX), provided the participant was receiving this medication during prior participation in MLN0002-2003.
4. The participant's vaccinations are up to date as per inclusion criteria number 10 in MLN0002-2003.

Exclusion Criteria:

1. Is female and is lactating or pregnant.
2. Has hypersensitivity or allergies to vedolizumab or any of its excipients.
3. Has withdrawn from Study MLN0002-2003.
4. Has developed any new unstable or uncontrolled cardiovascular, heart failure moderate to severe (New York Class Association III or IV), pulmonary, hepatic, renal, gastrointestinal (GI), genitourinary, hematological, coagulation, immunological, endocrine/metabolic, neurological, or other medical disorder that, in the opinion of the investigator, would confound the study results or compromise participant safety.
5. Has a positive progressive multifocal leukoencephalopathy (PML) subjective symptom checklist prior to the administration of the first dose of study drug.
6. Currently requires major surgical intervention for ulcerative colitis (UC) or CD (example, bowel resection), or is anticipated to require major surgical intervention for UC or CD during the study.
7. Has other serious comorbidities that will limit his or her ability to complete the study.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 2 Years to 17 Years (Child)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Belgium, Canada, France, Hungary, Israel, Netherlands, Poland, Ukraine, United Kingdom, United States

Administrative Information

• NCT Number: NCT03196427
• Other Study ID Numbers: Vedolizumab-2005; 2017-002182-21 ( EudraCT Number ); U1111-1176-5741 ( Other Identifier: WHO ); 17/NE/0258 ( Registry Identifier: NRES ); MOH_2017-09-18_000649 ( Other Identifier: CRS )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Yes
• Plan Description: Takeda provides access to the de-identified individual participant data (IPD) for eligible studies to aid qualified researchers in addressing legitimate scientific objectives (Takeda's data sharing commitment is available on https://clinicaltrials.takeda.com/takedas-commitment?commitment=5). These IPDs will be provided in a secure research environment following approval of a data sharing request, and under the terms of a data sharing agreement.
• Supporting Materials: Study Protocol
• Supporting Materials: Statistical Analysis Plan (SAP)
• Supporting Materials: Informed Consent Form (ICF)
• Supporting Materials: Clinical Study Report (CSR)
• Access Criteria: IPD from eligible studies will be shared with qualified researchers according to the criteria and process described on https://vivli.org/ourmember/takeda/. For approved requests, the researchers will be provided access to anonymized data (to respect patient privacy in line with applicable laws and regulations) and with information necessary to address the research objectives under the terms of a data sharing agreement.
• URL: https://vivli.org/ourmember/takeda/

• Responsible Party: Takeda
• Study Sponsor: Takeda

Collaborators

• Takeda Development Center Americas, Inc.
• Takeda Development Centre Europe Ltd.

Investigators

• Study Director: Medical Director; Takeda

• PRS Account: Takeda
• Verification Date: January 2021