Crohn's Disease, Ulcerative Colitis
Conditions
Keywords
Drug Therapy
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).
Interventions
DRUGVedolizumab
Vedolizumab intravenous infusion
Sponsors
Takeda
Takeda Development Center Americas, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
2 Years to 17 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Treatment-emergent Adverse Events (TEAEs) | From first dose of study drug up to end of follow up (up to 6.8 years) | AE defined as any untoward medical occurrence in clinical investigation participants administered drug; it does not necessarily have to have 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 was considered related to the drug. TEAE was defined as an AE whose date of onset occurred on or after the first dose of study drug, or an already-present AE that worsened in intensity or frequency following the treatment start, occurring from the first dose of study drug to the day of last dose of study drug. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With UC Who Achieved and Maintained Clinical Response Based on Complete Mayo Score | At Week 32 | Clinical response was defined as a continued reduction in complete Mayo score of \>=3 points and \>=30 percent (%) 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 less than or equal to (\<=1) point. Mayo score was an instrument designed to measure disease activity of UC. It consisted of 4 subscores: stool frequency, rectal bleeding, findings on endoscopy and physician rating of disease activity, each graded from 0 to 3 where 0 indicated normal and 3 indicated more severe disease. These scores were summed to give a total score range of 0 to 12; where higher scores indicated more severe disease. |
| Percentage of Participants With CD Who Achieved and Maintained Clinical Response Based on Simple Endoscopic Score for Crohn's Disease (SES-CD) Score and Crohn's Disease Activity Index (CDAI) at Week 32 | At Week 32 | Maintenance of clinical response based on SES-CD and CDAI was defined as a 50% reduction in SES-CD score on endoscopy compared to the baseline endoscopy \[at initiation of MLN0002-2003 (NCT03138655)\]; and continued reduction in CDAI that is a \>= 70 point decrease from the baseline CDAI score at the initiation of MLN0002-2003 (NCT03138655). CDAI was a research tool used to quantify the symptoms of participants with Crohn's disease. SES-CD consisted 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 indicated the presence of mucosal lesions. |
| Time to Major Inflammatory Bowel Disease (IBD) - Related Events | Up to 6.8 years | Time to major IBD-related events was defined as time from study treatment start to first major IBD-related hospitalization, surgery, or procedure due to UC and CD. |
| Change From Baseline in IMPACT-III - Total Score | Baseline, Weeks 24, 48, 72, 96, 120, 144, 168, 192, 216, 240, 264, 288, and 312 | The IMPACT-III questionnaire was 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 used a 5-point Likert scale ranging from 1 to 5 for all answers. The total score was obtained by summing individual domain scores. The total score ranged from 35 to 175, with higher scores suggesting better quality of life. |
| Change From Baseline in IMPACT-III - Bowel Symptoms Domain Score | Baseline, Weeks 24, 48, 72, 96, 120, 144, 168, 192, 216, 240, 264, 288, and 312 | The IMPACT-III questionnaire was a self-reported measure with 35 closed questions encompassing 6 domains. The Bowel Symptoms domain consisted of 7 items. Each item was scored using a 5-point Likert scale ranging from 1 to 5. The bowel symptoms domain score ranged from 7 to 35, with higher scores suggesting a better quality of life. |
| Change From Baseline in IMPACT-III - Systemic Symptoms Domain Score | Baseline, Weeks 24, 48, 72, 96, 120, 144, 168, 192, 216, 240, 264, 288, and 312 | The IMPACT-III questionnaire was a self-reported measure with 35 closed questions encompassing 6 domains. The systemic symptoms domain consisted of 3 items. Each item was scored using a 5-point Likert scale ranging from 1 to 5. The systemic symptoms domain score ranged from 3 to 15, with higher scores suggesting a better quality of life. |
| Change From Baseline in IMPACT-III - Social Functioning Domain Score | Baseline, Weeks 24, 48, 72, 96, 120, 144, 168, 192, 216, 240, 264, 288, and 312 | The IMPACT-III questionnaire was a self-reported measure with 35 closed questions encompassing 6 domains. The social functioning domain consisted of 12 items. Each item was scored using a 5-point Likert scale ranging from 1 to 5. The social functioning domain score ranged from 12 to 60, with higher scores suggesting a better quality of life. |
| Change From Baseline in IMPACT-III - Body Image Domain Score | Baseline, Weeks 24, 48, 72, 96, 120, 144, 168, 192, 216, 240, 264, 288, and 312 | The IMPACT-III questionnaire was a self-reported measure with 35 closed questions encompassing 6 domains. The body image domain consisted of 3 items. Each item was scored using a 5-point Likert scale ranging from 1 to 5. The body image domain score ranged from 3 to 15, with higher scores suggesting a better quality of life. |
| Change From Baseline in IMPACT-III - Treatment/Interventions Domain Score | Baseline, Weeks 24, 48, 72, 96, 120, 144, 168, 192, 216, 240, 264, 288, and 312 | The IMPACT-III questionnaire was a self-reported measure with 35 closed questions encompassing 6 domains. The treatment/interventions domain consisted of 3 items. Each item was scored using a 5-point Likert scale ranging from 1 to 5. The treatment/interventions domain score ranged from 3 to 15, with higher scores suggesting a better quality of life. |
| Change From Baseline in IMPACT-III - Emotional Functioning Domain Score | Baseline, Weeks 24, 48, 72, 96, 120, 144, 168, 192, 216, 240, 264, 288, and 312 | The IMPACT-III questionnaire was a self-reported measure with 35 closed questions encompassing 6 domains. The emotional functioning domain consisted of 7 items. Each item was scored using a 5-point Likert scale ranging from 1 to 5. The emotional functioning domain score ranged from 7 to 35, with higher scores suggesting a better quality of life. |
| Height Velocity at Week 48 and Every 48 Weeks | At Weeks 48, 96, 144, 192, 240, 288, and 336 | Height velocity (centimeter per year \[cm/year\]) was calculated as the change in height divided by the duration \[time between the two height measures\]. |
| Change From Baseline in Height | Baseline, Weeks 48, 96, 144, 192, 240, 288, 336 | Change from baseline in height was reported. |
| Change From Baseline in Weight | Baseline, Weeks 24, 48, 72, 96, 120, 144, 168, 192, 216, 240, 264, 288, 312, and 336 | Change from baseline in weight was reported. |
| Change From Baseline in Body Mass Index (BMI) | Baseline, Weeks 24, 48, 72, 96, 120, 144, 168, 192, 216, 240, 264, 288, 312, and 336 | BMI was calculated as Weight (in kilograms)/height (in meters square). |
| Percentage of Participants Who Achieved Tanner Stage V at or Before Age 16 (in Females) or Age 17 (in Males) | Up to 6.8 years | Tanner Stage Evaluation was 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 was assessed at or before age 16 years for females or 17 years for males. |
Countries
France, Hungary, Israel, Poland, Ukraine, United Kingdom, United States
Contacts
STUDY_DIRECTORStudy Director
Takeda
Participant flow
Recruitment details
A total of 59 participants with ulcerative colitis (UC) or Crohn's disease (CD) took part in the study across 34 investigative sites in Belgium, United States, France, Hungary, Israel, Poland, Ukraine, and United Kingdom from 30 July 2018 to 17 July 2025.
Pre-assignment details
Pediatric participants who had completed MLN0002-2003 (NCT03138655), and at Week 22, had achieved clinical response were enrolled to receive vedolizumab at the same dosage per body weight (\>= 30 kg and \< 30 kg). As per planned analysis, participants with disease worsening based on Pediatric Ulcerative Colitis Activity Index (PUCAI) or Pediatric Crohn's Disease Activity Index (PCDAI) scores escalated to vedolizumab IV from low to high doses (150 to 300 mg or 100 to 200 mg) at Week 40.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Customized Adolescents (12-17 years) | 7 Participants |
| Age, Customized Children (2-11 years) | 33 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 6 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants |
| Race (NIH/OMB) More than one race | 2 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) White | 8 Participants |
| Sex: Female, Male Female | 5 Participants |
| Sex: Female, Male Male | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 3 | 0 / 6 | 0 / 5 | 0 / 5 | 0 / 2 | 0 / 7 | 0 / 2 | 0 / 10 | 0 / 12 | 0 / 6 |
| other Total, other adverse events | 3 / 3 | 5 / 6 | 5 / 5 | 5 / 5 | 2 / 2 | 6 / 7 | 2 / 2 | 10 / 10 | 12 / 12 | 6 / 6 |
| serious Total, serious adverse events | 1 / 3 | 1 / 6 | 0 / 5 | 4 / 5 | 1 / 2 | 3 / 7 | 1 / 2 | 4 / 10 | 4 / 12 | 1 / 6 |
Outcome results
None listed