Clinical trial NCT03196427: 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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Ulcerative Colitis
Crohn's Disease
Keywords: Drug Therapy
Lead sponsor: Takeda
Sponsor class: INDUSTRY
Collaborators: name: Takeda Development Center Americas, Inc.
First posted: 2017-06-22
Enrollment: 59
Sex: ALL
Minimum age (years): 2
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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 continue receiving the same dose assigned from the parent study MLN0002-2003 \[NCT03138655\], which will remain blinded until week 40.

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 milligram \[mg\]) 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 will be until vedolizumab IV is commercially available for pediatric indication(s) in the participant's country or until other drug access programs become available (whichever comes first), the participant turns 18 years of age and can be transitioned to commercial drug, the participant withdraws from the study, or the sponsor decides to close the study (up to approximately 8 years).

Eligibility criteria: Inclusion Criteria:

1. Is male or female with UC or CD 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 \[mg/day\]) provided the participant was receiving this medication during prior participation in MLN0002-2003.
   * Topical (rectal) treatment with 5-ASA 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 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.

Primary outcomes:
measure: Percentage of Participants with Treatment-emergent Adverse Events (TEAEs)
timeFrame: Baseline up to approximately 8 years
Secondary outcomes:
measure: Percentage of Participants With UC Meeting Clinical Response Based on Complete Mayo Score at Week 32
timeFrame: Week 32
measure: Percentage of Participants With CD Meeting Clinical Response Based on 50 Percent (%) Reduction in Simple Endoscopic Score for Crohn's Disease (SES-CD) Score at Week 32
timeFrame: Week 32
measure: Time to Major Inflammatory Bowel Disease (IBD) - Related Events
timeFrame: Baseline up to approximately 8 years
measure: Change from Baseline in IMPACT-III Total and Subscale Scores at Week 24 and Every 24 weeks, Thereafter up to 8 Years
timeFrame: Baseline up to approximately 8 years
measure: Height Velocity at Week 48 and Every 48 weeks, Thereafter up to 8 Years
timeFrame: Baseline up to approximately 8 years
measure: Change from Baseline in Height at Week 24 and Every 24 Weeks, Thereafter up to 8 Years
timeFrame: Baseline up to approximately 8 years
measure: Change from Baseline in Weight at Week 24 and Every 24 Weeks, Thereafter up to 8 Years
timeFrame: Baseline up to approximately 8 years
measure: Change from Baseline in Body Mass Index (BMI) at Week 24 and Every 24 Weeks, Thereafter up to 8 Years
timeFrame: Baseline up to approximately 8 years
measure: Percentage of Participants Achieving Tanner Stage V
timeFrame: Baseline up to approximately 8 years
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Cedars-Sinai Medical Center
state: California
city: Orange
country: United States
facility: Children's Hospital of Orange County
state: California
city: San Francisco
country: United States
facility: University of California San Francisco
state: California
city: Hartford
country: United States
facility: Connecticut Children's Medical Center
state: Connecticut
city: Jacksonville
country: United States
facility: Nemours Childrens Specialty Care - Jacksonville
state: Florida
city: Atlanta
country: United States
facility: Children's Center for Digestive Healthcare
state: Georgia
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
city: Houston
country: United States
facility: Texas Children's Hospital
state: Texas
city: Seattle
country: United States
facility: Seattle Children's Hospital
state: Washington
city: Paris Cedex 15
country: France
facility: Hopital Necker-Enfants Malades
state: Ile-de-france
city: Miskolc
country: Hungary
facility: BAZ Megyei Korhaz es Egyetemi Oktatokorhaz
state: Borsod-abauj-zemplen
city: Szeged
country: Hungary
facility: Szegedi Tudomanyegyetem Szent-Gyorgyi Albert Klinikai Kozpont
state: Csongrad
city: Debrecen
country: Hungary
facility: Debreceni Egyetem Klinikai Kozpont
state: Hajdu-bihar
city: Ramat Gan
country: Israel
facility: The Edmond and Lily Safra Children's Hospital - Sheba Medical Center
state: Tel Aviv
city: Haifa
country: Israel
facility: Carmel Medical Center
city: Jerusalem
country: Israel
facility: Shaare Zedek Medical Center
city: Petach Tiqwa
country: Israel
facility: Schneider Children's Medical Center of Israel
city: Tel Aviv
country: Israel
facility: Tel Aviv Sourasky Medical Center
city: Lodz
country: Poland
facility: Centralny Szpital Kliniczny Uniwersytetu Medycznego w Lodzi Osrodek Pediatryczny im Marii Konopnic
state: Lodzkie
city: Krakow
country: Poland
facility: Uniwersytecki Szpital Dzieciecy w Krakowie
state: Malopolskie
city: Rzeszow
country: Poland
facility: Gabinet Lekarski Dr. Hab. N. Med. Bartosz Korczowski
state: Podkarpackie
city: Kharkiv
country: Ukraine
facility: Kharkiv Regional Clinical Children's Hospital
city: London
country: United Kingdom
facility: Barts and The London NHS Trust
state: England
Study officials:
affiliation: Takeda
name: Study Director
role: STUDY_DIRECTOR
References: