A Study of Vedolizumab in Children and Teenagers With Moderate to Severe Ulcerative Colitis

JRCT ID: jRCT2071210030

Registered date:31/05/2021

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: Colitis, Ulcerative
• Date of first enrollment: 19/10/2021
• Target sample size: 120
• Countries of recruitment: United States,Japan,Belgium,Japan,Bosnia,Japan,Croatia,Japan,Australia,Japan,Canada,Japan,Czech Republic,Japan,Germany,Japan,Hungary,Japan,Italy,Japan,Lithuania,Japan,Poland,Japan,New Zealand,Japan,Romania,Japan,Russia,Japan,Slovakia,Japan,Spain,Japan,United Kingdom,Japan,Israel,Japan,China,Japan,Ukraine,Japan
• Study type: Interventional

Intervention(s)

Induction Period: Participants >=30 kg, Vedolizumab 300 mg
Vedolizumab 300 mg, intravenous (IV) infusion, at Day 1, Weeks 2 and 6 in the Induction Period. Participants with UC having Baseline weight of >=30 kg are included in this arm.

Induction Period: Participants >15 to <30 kg, Vedolizumab 200 mg
Vedolizumab 200 mg, IV infusion, at Day 1, Weeks 2 and 6 in the Induction Period. Participants with UC having Baseline weight of >15 to <30 kg are included in this arm.

Induction Period: Participants 10 to 15 kg, Vedolizumab 150 mg
Vedolizumab 150 mg, IV infusion, at Day 1, Weeks 2 and 6 in the Induction Period. Participants with UC having Baseline weight of 10 to 15 kg are included in this arm.

Maintenance Period: Participants >=30 kg, Vedolizumab 300 mg
Vedolizumab 300 mg, IV infusion, once every 8 weeks (Q8W) from Week 14 up to Week 46 in the Maintenance Period. Participants with Week 14 weight of >=30 kg who achieved clinical response at Week 14 randomized to this high dose arm group will receive vedolizumab 300 mg.

Maintenance Period: Participants >=30 kg, Vedolizumab 150 mg
Vedolizumab 150 mg, IV infusion, Q8W from Week 14 up to Week 46 in the Maintenance Period. Participants with Week 14 weight of >=30 kg who achieved clinical response at Week 14 randomized to this low dose arm group will receive vedolizumab 150 mg.

Maintenance Period: Participants >15 to <30 kg, Vedolizumab 200 mg
Vedolizumab 200 mg, IV infusion, Q8W from Week 14 up to Week 46 in the Maintenance Period. Participants with Week 14 weight of >15 to <30 kg who achieved clinical response at Week 14 randomized to this high dose arm group will receive vedolizumab 200 mg.

Maintenance Period: Participants >15 to <30 kg, Vedolizumab 100 mg
Vedolizumab 100 mg, IV infusion, Q8W from Week 14 up to Week 46 in the Maintenance Period. Participants with Week 14 weight of >15 to <30 kg who achieved clinical response at Week 14 randomized to this low dose arm group will receive vedolizumab 100 mg.

Maintenance Period: Participants 10 to 15 kg, Vedolizumab 150 mg
Vedolizumab 150 mg, IV infusion, Q8W from Week 14 up to Week 46 in the Maintenance Period. Participants with Week 14 weight of 10 to 15 kg who achieved clinical response at Week 14 randomized to this high dose arm group will receive vedolizumab 150 mg.

Maintenance Period: Participants 10 to 15 kg, Vedolizumab 100 mg
Vedolizumab 100 mg, IV infusion, Q8W from Week 14 up to Week 46 in the Maintenance Period. Participants with Week 14 weight of 10 to 15 kg who achieved clinical response at Week 14 randomized to this low dose arm group will receive vedolizumab 100 mg.

Outcome(s)

Primary Outcome

1.Percentage of Participants with Clinical Remission at Week 54 Based on Modified Mayo Score
Time Frame: Week 54
Clinical remission based on the modified Mayo score is defined as stool frequency subscore 0 to 1 and a decrease of 1 or more from Baseline; rectal bleeding subscore of 0; and, endoscopy subscore 0 to 1 (modified so that a score of 1 does not include friability). Mayo score is an instrument designed to measure disease activity of UC. Modified Mayo score consists of 3 sub-scores: stool frequency, rectal bleeding, and Mayo endoscopic subscore (findings on endoscopy). Each subscale is 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 9. Here, higher score indicates more severe disease.

Secondary Outcome

1.Percentage of Participants with Clinical Remission at Week 14 Based on Modified Mayo Score
Time Frame: Week 14

2.Percentage of Participants with Sustained Clinical Remission at Week 14 Based on Modified Mayo Score
Time Frame: Week 14
Sustained clinical remission is where a participant achieves clinical remission at Weeks 14 and 54, based on the modified Mayo score.

3.Percentage of Participants with Sustained Clinical Remission at Week 54 Based on Modified Mayo Score
Time Frame: Week 54

4.Percentage of Participants with Sustained Endoscopic Remission at Week 14
Time Frame: Week 14
Sustained endoscopic remission was defined as Mayo endoscopic score (MES) of <=1 point. MES is a subscale of the Mayo score, an instrument designed to measure disease activity of UC. The subscale is graded from 0 to 3 based on the findings on endoscopy where 0=normal or inactive disease, 1=mild disease (erythema, decreased vascular pattern), 2=moderate disease (marked erythema, lack of vascular pattern, friability, erosions), 3=severe disease (spontaneous bleeding, ulceration). Higher scores indicate more severe disease.

5.Percentage of Participants with Sustained Endoscopic Remission at Week 54
Time Frame: Week 54

6.Percentage of Participants with Endoscopic Response at Week 14
Time Frame: Week 14
Endoscopic response was defined as a decrease in MES by >=1 grade. MES is a subscale of the Mayo score, an instrument designed to measure disease activity of UC. The subscale is graded from 0 to 3 based on the findings on endoscopy where 0=normal or inactive disease, 1=mild disease (erythema, decreased vascular pattern), 2=moderate disease (marked erythema, lack of vascular pattern, friability, erosions), 3=severe disease (spontaneous bleeding, ulceration). Higher scores indicate more severe disease.

7.Percentage of Participants with Endoscopic Response at Week 54
Time Frame: Week 54

8.Percentage of Participants with Corticosteroid-free Clinical Remission at Week 54
Time Frame: Week 54
Corticosteroid-free clinical remission is where a participant achieves clinical remission at Week 54, and was off corticosteroids at least 12 weeks prior to and at Week 54. Clinical remission based on the modified Mayo score is defined as stool frequency subscore 0 to 1 and a decrease of 1 or more from Baseline; rectal bleeding subscore of 0; and, endoscopy subscore 0 to 1 (modified so that a score of 1 does not include friability). Mayo score is an instrument designed to measure disease activity of UC. Modified Mayo score consists of 3 sub-scores: stool frequency, rectal bleeding, and Mayo endoscopic subscore (findings on endoscopy). Each subscale is 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 9. Here, higher score indicates more severe disease.

9.Percentage of Participants with Clinical Remission at Week 54 Based on Complete Mayo Score
Time Frame: Week 54
Clinical remission based on the complete Mayo score is where a participant achieved a complete Mayo score =<2 points with no individual subscore >1 at Week 54. Mayo score is an instrument designed to measure disease activity of UC. Complete Mayo score consists of 4 sub-scores: stool frequency, rectal bleeding, Mayo endoscopic subscore (findings on endoscopy), and Physician's global assessment. Each subscale is 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. Here, higher score indicates more severe disease.

10.Serum Trough Concentrations of Vedolizumab over Time
Time Frame: Predose and postdose at multiple time points (up to 54 weeks)

11.Percentage of Participants with Positive Anti-vedolizumab Antibodies (AVA)
Time Frame: Predose (up to 54 weeks)

12.Percentage of Participants with Positive Neutralizing AVA
Time Frame: Predose (up to 54 weeks)

13.Percentage of Participants with Sustained Clinical Response at Week 14 Based on Complete Mayo Score
Time Frame: Week 14
Clinical response is where a participant has a reduction in complete Mayo score of >=3 points and >=30% from Baseline with an accompanying decrease in rectal bleeding subscore of >=1 point or absolute rectal bleeding subscore of <=1 point. Mayo score is an instrument designed to measure disease activity of UC. Complete Mayo score consists of 4 sub-scores: stool frequency, rectal bleeding, Mayo endoscopic subscore (findings on endoscopy), and Physician's global assessment. Each subscale is 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. Here, higher score indicates more severe disease.

14.Percentage of Participants with Sustained Clinical Response at Week 54 Based on Complete Mayo Score
Time Frame: Week 54

15.Percentage of Participants with Clinical Response up to Week 54 Based on Partial Mayo Score
Time Frame: Weeks 2, 6, 10, 14, 22, 30, 38, 46, and 54
Clinical response is defined as reduction of >=2 points and >=25% from the Baseline partial Mayo score, including a >=1-point decrease in the Mayo stool frequency subscore and a >=1-point reduction in the rectal bleeding subscore or absolute rectal bleeding subscore of =<1 point. Partial Mayo score consists of 3 sub-scores: stool frequency, rectal bleeding, and Physician's global assessment. Each subscale is 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 9. Higher score indicates more severe disease.

16.Percentage of Participants with Clinical Remission up to Week 54 Based on Partial Mayo Score
Time Frame: Weeks 2, 6, 10, 14, 22, 30, 38, 46, and 54
A partial Mayo score <=2 points and no individual subscore >1 point.

17.Percentage of Participants with at least One Adverse Event (AE), Serious Adverse Event (SAE), and Adverse Event of Special Interest (AESI)
Time Frame: Up to 158 weeks
An AE is defined as any untoward medical occurrence in a clinical investigation participant administered a drug which does not necessarily have to have a causal relationship with the treatment. An SAE is defined as any untoward medical occurrence that at any dose: results in death, is life threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, leads to a congenital anomaly/birth defect and/or is an important medical event. An AESI (serious or non-serious) is one of scientific and medical concern specific to the compound or program, for which ongoing monitoring and rapid communication by the investigator to Takeda may be appropriate. AESIs include: infusion-related reactions and hypersensitivity, serious infection, malignancy, or other (liver injury and PML).

18.Change from Baseline in Weight
Time Frame: Baseline, up to Week 54
Change from in Baseline in weight will be calculated as: Weight at each study visit (up to Week 54) - Weight at Baseline.

19.Change from Baseline in Linear Growth Z-score
Time Frame: Baseline, up to Week 54
Linear growth Z-score will be calculated as: Z-score = (observed value - median value of the reference population) / standard deviation value of reference population.

20.Change in Tanner Stage at Week 54 Compared with Baseline
Time Frame: Week 54
Tanner Stage is used to measure pubertal development. Female (F) and male (M) participants are evaluated for breast development and genital development respectively and both genders for pubic hair development. Tanner Stage is based on progression through 5-stages.

Key inclusion & exclusion criteria

• Age minimum: >= 2age old
• Age maximum: <= 17age old
• Gender: Both

Include criteria

1.Has moderately to severely active ulcerative colitis (UC), unresponsive or intolerant to their current standard of care (SOC).
2.Weighs >=10 kg at the time of screening and enrollment into the study.
3.Participants with UC diagnosed at least 1 month before screening. Participants with moderately to severely active UC based on a modified Mayo score of 5 to 9 (sum of Mayo endoscopic subscore, stool frequency subscore, and rectal bleeding subscore) with a Mayo endoscopic subscore of >=2 (with the presence of mucosal friability excluding an endoscopic subscore of 1 and mandating a score of at least 2) at screening endoscopy.
4.Has failed, lost response to, or been intolerant to treatment with at least 1 of the following agents: corticosteroids (eg, azathioprine [AZA], 6-mercaptopurine [6-MP], methotrexate [MTX]), immunomodulators, and/or tumor necrosis factor alpha (TNF-alfa) antagonist therapy (eg, infliximab, adalimumab). This includes participants who are dependent on corticosteroids to control symptoms and who are experiencing worsening of disease in the moderate-to-severe range when attempting to wean off corticosteroids.
5.Has evidence of UC extending proximal to the rectum (i.e., not limited to proctitis), at a minimum.
6.Has extensive colitis or pancolitis of >8 years' duration or left-sided colitis of >12 years' duration must have documented evidence of a negative surveillance colonoscopy within 12 months before screening.
7.Participants with vaccinations that are up-to-date based on the countrywide, accepted schedule of childhood vaccines.

Exclude criteria

1.Has previous exposure to approved or investigational anti-integrins including, but not limited to natalizumab, efalizumab, etrolizumab, or Abrilumab (AMG 181), or mucosal addressin cell adhesion molecule-1 (MAdCAM-1) antagonists or rituximab.
2.Has received an investigational biologic within 60 days or 5 half-lives before screening (whichever is longer); or an approved biologic or biosimilar agent within 2 weeks before the first dose of study drug or at any time during the screening period.
3.Has active cerebral/meningeal disease, signs/symptoms or history of progressive multifocal leukoencephalopathy (PML) or any other major neurological disorders including stroke, multiple sclerosis, brain tumor or neurodegenerative disease.
4.Has had clinically significant infection (eg, pneumonia, pyelonephritis, coronavirus disease 2019 [COVID-19]) within 30 days prior to first dose of study drug.
5.Has received any live vaccinations within 30 days prior to first dose of study drug.
6.Participants who currently require surgical intervention or are anticipated to require surgical intervention for UC during this study.
7.Has had subtotal or total colectomy or have a jejunostomy, ileostomy, colostomy, ileo-anal pouch, or known fixed stenosis of the intestine.
8.Participants with a current diagnosis of indeterminate colitis.
9.Participants with clinical features suggesting monogenic very early onset inflammatory bowel disease.
10.Participant with active or latent tuberculosis (TB), as evidenced by a diagnostic TB test performed within 30 days of screening or during the screening period that is positive, defined as:
-Positive QuantiFERON test or 2 successive indeterminate QuantiFERON tests, OR
-A TB skin test reaction >=5 mm.
NOTE: If participants have received Bacillus Calmette-Guerin vaccine then a QuantiFERON TB Gold test should be performed instead of the TB skin test.
11.Participants with evidence of positive hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb). Hepatitis B virus (HBV) immune participants (ie, hepatitis B surface antigen [HBsAg]-negative and hepatitis B antibody-positive) may, however, be included. Note: If a participant tests negative for HBsAg, but positive for HBcAb, the participant would be considered eligible if the absence of HBV DNA is confirmed by HBV DNA polymerase chain reaction reflex testing performed in the central laboratory.
12.Participants with chronic hepatitis C virus (HCV) (ie, positive HCV antibody [HCVAb] and HCV RNA). Note: Subjects who are HCVAb-positive without evidence of HCV RNA may be considered eligible (spontaneous viral clearance or previously treated and cured [defined as no evidence of HCV RNA at least 12 weeks before baseline]).
13.The participant has evidence of dysplasia or history of malignancy other than a successfully treated nonmetastatic cutaneous squamous cell or basal cell carcinoma or localized carcinoma in situ of the cervix.
14.Has positive stool studies for ova and/or parasites or stool culture at screening visit.
15.Has positive Clostridioides difficile (C difficile) stool test at screening visit.

Other inclusion/exclusion criteria may apply.

Related Information

• Primary Sponsor: Shikamura Mitsuhiro
• Secondary ID(s): NCT04779307,2020-004300-34