A Study of Vedolizumab in Children With Ulcerative Colitis (UC) or Crohn's Disease (CD)

Ulcerative Colitis Clinical Trial

Official title:

A Phase 3b Extension Study to Evaluate the Long-term Safety of Vedolizumab Intravenous in Pediatric Patients With Ulcerative Colitis or Crohn's Disease

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05442567
• Other study ID #: MLN0002-3029
• Secondary ID: 2021-000630-34jR
• Status: Recruiting
• Phase: Phase 3
• Start date: May 16, 2023
• Est. completion date: August 15, 2031

Study information

• Verified date: March 2024
• Source: Takeda
• Contact: Takeda Contact
• Phone: +1-877-825-3327
• Email: medinfoUS[@]takeda.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The study is an extension of two parent studies (MLN0002-3024 [NCT04779307] and MLN0002-3025 [NCT04779320]). Participants must have participated in one of the previous studies. The purpose of this study is to collect the long-term safety of vedolizumab in children with UC or CD.

Description:

This multi-center trial is conducted worldwide. Up to 240 patients would be enrolled from Studies MLN0002-3024 [participants with UC] and MLN0002-3025 [participants with CD], either in the Treatment Cohort or in the Observational Cohort. Approximately 93 participants who have previously participated either in study MLN0002-3024 or MLN0002-3025, referred to as parent study, are expected to roll over to the MLN0002-3029 study in the treatment cohort.

Treatment Cohort:

The drug being tested in this study is called vedolizumab, being studied to treat pediatric patients who have UC or CD.

Participants eligible for the Treatment Cohort can be administered vedolizumab intravenous (IV) at Week 54 visit of parent study or up to 1 week after Week 54 of the parent study based on the availability of test results needed to assess eligibility of the participant. At this study entry, participants will be administered the same blinded dose of vedolizumab IV that was received at Week 46 in the parent study and will then continue to receive vedolizumab IV at a frequency of once every 8 weeks (Q8W) in the following treatment groups:

• Participants 10 to ≤15 kilogram (kg), Vedolizumab 150 milligram (mg) (High dose)

• Participants 10 to ≤15 kg, Vedolizumab 100 mg (Low dose)

• Participants >15 to <30 kg, Vedolizumab 200 mg (High dose)

• Participants >15 to <30 kg, Vedolizumab 100 mg (Low dose)

• Participants ≥30 kg, Vedolizumab 300 mg (High dose)

• Participants ≥30 kg, Vedolizumab 150 mg (Low dose)

Blinding of dose group assignment of the parent study will continue until the final database lock of the parent study in order to protect the blinding of the parent study.

The overall time to participate in the Treatment Cohort of this study is up to participant withdrawal, or until vedolizumab IV is commercially available for pediatric indication(s) in the participant's country or until other drug access programs become available, or Sponsor's decision for study closure, or for up to approximately 5 years, whichever comes first. Participants who complete or are discontinued from the study for any reason will complete the final safety/end of study (EOS) visit 18 weeks after their last dose of study drug.

Observational Cohort:

Participants who received at least 1 dose of study drug during parent study and early terminated or are not eligible for the Treatment Cohort of this study after completion of the Week 54 visit of parent study, will be enrolled in the Observational Cohort of this study as part of a long-term follow-up period to assess prespecified safety events of interest and will not receive continued treatment with vedolizumab IV.

The overall time to participate in the Observational Cohort is up to approximately 2 years.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 240
• Est. completion date: August 15, 2031
• Est. primary completion date: August 15, 2031
• Accepts healthy volunteers: No
• Gender: All
• Age group: 2 Years and older

Eligibility

Main Inclusion Criteria:

For Treatment Cohort:

1. The participant should have completed Study MLN0002-3024 or Study MLN0002-3025 and achieved corticosteroid-free clinical response at Week 54 (and has tapered off of steroids, as applicable, at least 12 weeks before Week 54) as defined by a reduction of partial Mayo score of =2 points and =25% from baseline for participants with UC, or by a decrease of pediatric Crohn's disease activity index (PCDAI) of =15 points for participants with CD and with total PCDAI =30.

2. A male participant who is sexually active with a female partner of childbearing potential agrees to use barrier method of contraception (e.g., condom with or without spermicide) from signing of informed consent throughout the duration of the study and for 18 weeks after last dose. The female partner of a male participant should also be advised to use a highly effective method of contraception.

3. A female participant of childbearing potential who is sexually active with a nonsterilized male partner agrees to use a highly effective method of contraception from signing of informed consent throughout the duration of the study and 18 weeks after the last dose.

For Observational Cohort:

1. The participant has received at least 1 dose of vedolizumab during Study MLN0002-3024 or Study MLN0002-3025 and early terminated OR completed the Week 54 visit of Study MLN0002-3024 or Study MLN0002-3025 but was not eligible to enroll in the treatment cohort of this study.

Main Exclusion Criteria:

For Treatment Cohort only:

1. The participant currently requires major surgical intervention for UC or CD (e.g., bowel resection), or is anticipated to require major surgical intervention for UC or CD during the study.

2. The participant 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.

3. The participant has other serious comorbidities that will limit their ability to complete the study.

4. The participant is unable to comply with all study assessments.

5. The participant has hypersensitivity or allergies to any of the vedolizumab excipients.

6. The participant is lactating or pregnant.

Related Conditions & MeSH terms

• Colitis
• Colitis, Ulcerative
• Crohn Disease
• Crohn's Disease
• Ulcer
• Ulcerative Colitis

Intervention

Drug:
• Vedolizumab IV
Vedolizumab IV infusion

Other:
• No Intervention
Participants will not receive any intervention in the Observational Cohort.

Locations

Country	Name	City	State
Australia	Monash Health, Monash Medical Centre	Clayton	Victoria
Australia	Royal Children's Hospital Melbourne - PIN	Parkville	Victoria
Australia	Queensland Childrens Hospital	South Brisbane	Queensland
Australia	Children's Hospital at Westmead	Westmead	New South Wales
Belgium	UZ Antwerpen	Edegem	Antwerpen
Belgium	Universitair Ziekenhuis Brussel - PIN	Jette	Brussels
Belgium	UZ Leuven	Leuven	Vlaams Brabant
Canada	University of Alberta Hospital	Edmonton	Alberta
Canada	London Health Sciences Centre	London	Ontario
Canada	British Columbia Children's Hospital	Vancouver	British Columbia
China	Beijing Children Hospital,Capital Medical University	Beijing	Beijing
China	The Children's Hospital Zhejiang UniversitySchool of Medicine	Hangzhou	Zhejiang
China	Children's Hospital of Fudan University	Shanghai	Shanghai
China	Henan Children's Hospital (Zhengzhou Children's Hospital)	Zhengzhou	Henan
Croatia	Klinika Za Djecje Bolesti Zagreb	Zagreb	Grad Zagreb
Greece	Attikon University General Hospital	Athens	Attiki
Greece	Children's Hospital "Agia Sofia"	Athens
Greece	Ippokratio General Hospital of Thessaloniki	Thessaloniki
Hungary	Semmelweis Egyetem	Budapest
Hungary	Borsod-Abauj-Zemplen Megyei Kozponti Korhaz es Egyetemi Oktato Korhaz	Miskolc	Borsod-Abauj-Zemplen
Israel	Carmel Medical Center	Haifa
Israel	Rambam Medical Center - PPDS	Haifa
Israel	Hadassah Medical Center - PPDS	Jerusalem	Yerushalayim
Israel	Shaare Zedek Medical Center	Jerusalem
Israel	Schneider Childrens Medical Center of Israel Petah Tikvah PIN	Petah Tikva	HaMerkaz
Israel	Tel Aviv Sourasky Medical Center PPDS	Tel-Aviv
Italy	Azienda USL di Bologna	Bologna	Emilia-Romagna
Italy	Fondazione IRCCS San Gerardo dei Tintori - ASST di Monza A. O. San Gerardo	Monza	Lombardia
Italy	AOU dell'Universita degli Studi della Campania Luigi Vanvitelli	Napoli	Campania
Italy	Azienda Ospedaliera Universitaria Federico II	Napoli	Campania
Italy	Universita degli Studi di Padova	Padova	Veneto
Italy	Sapienza University of Rome	Roma	Lazio
Japan	Juntendo University Hospital	Bunkyo-Ku	Tokyo
Japan	Japanese Red Cross Kumamoto Hospital	Kumamoto-shi	Kumamoto
Japan	Kurume University Hospital	Kurume-Shi	Hukuoka
Japan	National Center for Child Health and Development	Setagaya-Ku	Tokyo
Korea, Republic of	Kyungpook National University Chilgok hospital	Daegu	Daegu Gwang'yeogsi
Korea, Republic of	Gachon University Gil Medical Center	Incheon	Incheon Gwang'yeogsi
Korea, Republic of	Samsung Medical Center - PPDS	Seoul
Korea, Republic of	Seoul National University Hospital	Seoul
Poland	Gornoslaskie Centrum Zdrowia Dziecka Im. Sw. Jana Pawla II Spsk Nr 6 Sum W Katowicach	Katowice	Slaskie
Poland	Uniwersytecki Szpital Dzieciecy	Krakow	Malopolskie
Poland	Instytut Centrum Zdrowia Matki Polki	Lodz	Lodzkie
Poland	SPZOZ Centralny Szpital Kliniczny UM w Lodzi	Lodz
Poland	Korczowski Bartosz, Gabinet Lekarski	Rzeszow	Podkarpackie
Poland	Twoja Przychodnia SCM	Szczecin	Zachodniopomorskie
Poland	Instytut Pomnik Centrum Zdrowia Dziecka	Warszawa	Mazowieckie
Poland	WIP Warsaw IBD Point Profesor Kierkus	Warszawa	Mazowieckie
Slovakia	Narodny ustav detskych chorob	Bratislava
United Kingdom	Birmingham Children's Hospital NHS Foundation Trust	Birmingham	West Midlands
United Kingdom	Noahs Ark Childrens Hospital for Wales - PPDS - PIN	Cardiff	South Glamorgan
United Kingdom	Barts Health NHS Trust	London
United Kingdom	Great Ormond Street Hospital (GOSH)	London	London, City Of
United Kingdom	Royal Manchester Children's Hospital - PPDS	Manchester
United States	Childrens Center For Digestive Healthcare	Atlanta	Georgia
United States	Johns Hopkins University	Baltimore	Maryland
United States	Boston Children's Hospital	Boston	Massachusetts
United States	University Hospitals Cleveland Medical Center	Cleveland	Ohio
United States	Texas Children's Hospital	Houston	Texas
United States	MNGI Digestive Health PA-Plymouth	Minneapolis	Minnesota
United States	Goryeb Children's Hospital	Morristown	New Jersey
United States	The Steven and Alexandra Cohen Childrens Medical Center of New York - BRANY - PPDS	New Hyde Park	New York
United States	Advocate Children's Hospital Park Ridge	Park Ridge	Illinois
United States	Phoenix Childrens Hospital -1919 E Thompson Rd	Phoenix	Arizona
United States	Children's Hospital of Pittsburgh	Pittsburgh	Pennsylvania
United States	Carilion Children's Tanglewood Center	Roanoke	Virginia
United States	Mayo Clinic - PIN	Rochester	Minnesota
United States	Rady Childrens Hospital San Diego - PIN	San Diego	California

Sponsors (1)

Lead Sponsor	Collaborator
Takeda

Countries where clinical trial is conducted

United States,  Australia,  Belgium,  Canada,  China,  Croatia,  Greece,  Hungary,  Israel,  Italy,  Japan,  Korea, Republic of,  Poland,  Slovakia,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Treatment Cohort: Number of Participants With at Least One Adverse Event (AE)	An AE is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have causal relationship with this treatment. AE can be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a drug whether or not it is considered related to drug.	From first dose of study drug up to approximately 5 years
Primary	Observational Cohort: Number of Participants With Prespecified Safety Events	Prespecified safety events will include serious infections, malignancies, progressive multifocal leukoencephalopathy (PML), concerns about growth and pubertal development, and bowel surgery.	Up to approximately 2 years
Secondary	Treatment Cohort: Time to Major Inflammatory Bowel Disease (IBD)-related Events	Major IBD-related events include hospitalizations, surgeries, and procedures in pediatric participants with UC or CD.	Up to approximately 5 years
Secondary	Treatment Cohort: Change From Baseline of Studies MLN0002-3024 (UC) or MLN0002-3025 (CD) in IMPACT-III Total Score for Participants Aged 9 to 17 Years for Every 24 Weeks	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 (bad 'quality of life' condition) to 5 (good 'quality of life' condition) for all answers. The total score is an average of all item scores. The outcome score ranges from 35 to 175, with higher scores suggesting better quality of life. This outcome will be assessed in participants who were aged 9 to 17 years at the time of first dose of study drug in study MLN0002-3024 or MLN0002-3025. Baseline refers to the Baseline of study MLN0002-3024 or MLN0002-3025.	Baseline, every 24 weeks in this study (up to approximately 5 years)
Secondary	Treatment Cohort: Change From Baseline of Studies MLN0002-3024 (UC) or MLN0002-3025 (CD) in IMPACT-III Bowel Symptom Subscale Score for Participants Aged 9 to 17 Years for Every 24 Weeks	The IMPACT-III Bowel Symptom Subscale is a self-reported measure with 7 closed questions. It uses a 5-point Likert scale ranging from 1 (bad 'quality of life' condition) to 5 (good 'quality of life' condition) for all answers. The bowel symptom subscale score ranges from 1 to 35, with higher scores indicating lesser bowel symptoms. This outcome will be assessed in participants who were aged 9 to 17 years at the time of first dose of study drug in study MLN0002-3024 or MLN0002-3025. Baseline refers to the Baseline of study MLN0002-3024 or MLN0002-3025.	Baseline, every 24 weeks in this study (up to approximately 5 years)
Secondary	Treatment Cohort: Change From Baseline of Studies MLN0002-3024 (UC) or MLN0002-3025 (CD) in IMPACT-III Systemic Symptom Subscale Score for Participants Aged 9 to 17 Years for Every 24 Weeks	The IMPACT-III Systemic Symptom Subscale is a self-reported measure with 3 closed questions. It uses a 5-point Likert scale ranging from 1 (bad 'quality of life' condition) to 5 (good 'quality of life' condition) for all answers. The Systemic symptom subscale score ranges from 1 to 15, with higher scores indicating lesser systemic symptoms. This outcome will be assessed in participants who were aged 9 to 17 years at the time of first dose of study drug in study MLN0002-3024 or MLN0002-3025. Baseline refers to the Baseline of study MLN0002-3024 or MLN0002-3025.	Baseline, every 24 weeks in this study (up to approximately 5 years)
Secondary	Treatment Cohort: Change From Baseline of Studies MLN0002-3024 (UC) or MLN0002-3025 (CD) in IMPACT-III Social Functioning Subscale Score for Participants Aged 9 to 17 Years for Every 24 Weeks	The IMPACT-III Social Functioning Subscale is a self-reported measure with 12 closed questions. It uses a 5-point Likert scale ranging from 1 (bad 'quality of life' condition) to 5 (good 'quality of life' condition) for all answers. The social functioning subscale score ranges from 1 to 60, with higher scores indicating better social functioning. This outcome will be assessed in participants who were aged 9 to 17 years at the time of first dose of study drug in study MLN0002-3024 or MLN0002-3025. Baseline refers to the Baseline of study MLN0002-3024 or MLN0002-3025.	Baseline, every 24 weeks in this study (up to approximately 5 years)
Secondary	Treatment Cohort: Change From Baseline of Studies MLN0002-3024 (UC) or MLN0002-3025 (CD) in IMPACT-III Body Image Subscale Score for Participants Aged 9 to 17 Years for Every 24 Weeks	The IMPACT-III Body Image Subscale is a self-reported measure with 3 closed questions. It uses a 5-point Likert scale ranging from 1 (bad 'quality of life' condition) to 5 (good 'quality of life' condition) for all answers. The body image subscale score ranges from 1 to 15, with higher scores indicating better body image. This outcome will be assessed in participants who were aged 9 to 17 years at the time of first dose of study drug in study MLN0002-3024 or MLN0002-3025. Baseline refers to the Baseline of study MLN0002-3024 or MLN0002-3025.	Baseline, every 24 weeks in this study (up to approximately 5 years)
Secondary	Treatment Cohort: Change From Baseline of Studies MLN0002-3024 (UC) or MLN0002-3025 (CD) in IMPACT-III Treatment/Intervention Subscale Score for Participants Aged 9 to 17 Years for Every 24 Weeks	The IMPACT-III Treatment/Intervention Subscale is a self-reported measure with 3 closed questions. It uses a 5-point Likert scale ranging from 1 (bad 'quality of life' condition) to 5 (good 'quality of life' condition) for all answers. The treatment/intervention subscale score ranges from 1 to 15, with higher scores indicating ease of administration of treatment/interventions. This outcome will be assessed in participants who were aged 9 to 17 years at the time of first dose of study drug in study MLN0002-3024 or MLN0002-3025. Baseline refers to the Baseline of study MLN0002-3024 or MLN0002-3025.	Baseline, every 24 weeks in this study (up to approximately 5 years)
Secondary	Treatment Cohort: Change From Baseline of Studies MLN0002-3024 (UC) or MLN0002-3025 (CD) in IMPACT-III Emotional Functioning Subscale Score for Participants Aged 9 to 17 Years for Every 24 Weeks	The IMPACT-III Emotional Functioning Subscale is a self-reported measure with 7 closed questions. It uses a 5-point Likert scale ranging from 1 (bad 'quality of life' condition) to 5 (good 'quality of life' condition) for all answers. The emotional functioning subscale score ranges from 1 to 35, with higher scores indicating better emotional functioning. This outcome will be assessed in participants who were aged 9 to 17 years at the time of first dose of study drug in study MLN0002-3024 or MLN0002-3025. Baseline refers to the Baseline of study MLN0002-3024 or MLN0002-3025.	Baseline, every 24 weeks in this study (up to approximately 5 years)