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

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Takeda Development Center Americas Inc.

Participant type

Pediatric, Patients

Age range

0-17 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Digestive System Diseases [C06]

Trial duration

17 Dec 2021 → 1 Jul 2025

Decision date (initial)

2024-06-18

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Takeda Development Center Americas, Inc.

External identifiers

EU CT number

2023-509018-12-00

EudraCT number

2020-004300-34

WHO UTN

U1111-1146-5451

ClinicalTrials.gov

NCT04779307

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Others, Efficacy, Pharmacokinetic

The primary objective of this study is to evaluate the efficacy of 2 different dose regimens of vedolizumab IV in pediatric subjects with moderately to severely active UC during maintenance therapy, based on clinical remission at Week 54.

Secondary objectives 12

1. • The efficacy of high and low doses of vedolizumab IV in pediatric subjects with moderately to severely active UC, based on clinical remission at Week 14.
2. • The efficacy of high and low doses of vedolizumab IV as measured by sustained clinical remission at Weeks 14 and 54."
3. • The efficacy of high and low doses of vedolizumab IV as measured by sustained clinical response at Weeks 14 and 54.
4. • The efficacy of high and low doses of vedolizumab IV as measured by sustained endoscopic remission at Weeks 14 and 54.
5. • The efficacy of high and low doses of vedolizumab IV as measured by endoscopic response at Weeks 14 and 54.
6. • The effect of high and low doses of vedolizumab IV on achieving corticosteroid-free remission at Week 54.
7. • The effect of high and low doses of vedolizumab IV on clinical response over time up to Week 54."
8. • The efficacy of high and low doses of vedolizumab IV as measured by clinical remission over time up to Week 54.
9. • Vedolizumab PK in pediatric subjects with moderately to severely active UC after IV administration.
10. • Safety in pediatric subjects on maintenance therapy up to Week 54.
11. • The immunogenicity of vedolizumab in pediatric subjects with moderately to severely active UC treated with vedolizumab IV.
12. • The effect of vedolizumab on patterns of growth and pubertal development in pediatric subjects with moderately to severely active UC during their participation in the study."" "

Conditions and MedDRA coding

Moderately to severely active Ulcerative Colitis (UC)

Study design 2 periods

Regulatory references

EMA paediatric investigation plan (PIP)

EMEA-000645-PIP01-09

Plan to share IPD

Yes

IPD 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.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

1. The subject is aged 2 to 17 years, inclusive, at the time of screening and enrollment into the maintenance phase of the study.
2. The subject weighs ≥10 kg at the time of screening and enrollment into the study.
3. Subjects with UC diagnosed at least 1 month before screening. Subjects 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. Subjects who have failed, lost response to, or been intolerant to treatment with at least 1 of the following agents: corticosteroids, immunomodulators (eg, AZA, 6-MP, MTX), and/or TNF-α antagonist therapy (eg, infliximab, adalimumab). This includes subjects 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. Subjects with evidence of UC extending proximal to the rectum (ie, not limited to proctitis), at a minimum.
6. Subjects with 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. Subjects with vaccinations that are up-to-date based on the countrywide, accepted schedule of childhood vaccines.

Exclusion criteria 10

1. 1.     Subjects who have had previous exposure to approved or investigational anti-integrins including, but not limited to natalizumab, efalizumab, etrolizumab, or AMG 181, or MAdCAM-1 antagonists or rituximab.
2. 2.     Subjects who have had prior exposure to vedolizumab.
3. 3.     Subjects with hypersensitivity or allergies to vedolizumab or any of its excipients.
4. 4.     Subjects who have received either (1) an investigational biologic (other than those listed in Exclusion Criterion #1) within 60 days or 5 half-lives before screening (whichever is longer); or (2) an approved biologic or biosimilar agent within 2 weeks before the first dose of study drug or at any time during the screening period.
5. 5.     Subjects with active cerebral/meningeal disease, signs/symptoms or history of PML or any other major neurological disorders including stroke, multiple sclerosis, brain tumor or neurodegenerative disease.
6. 8.     Subjects who currently require surgical intervention or are anticipated to require surgical intervention for UC during this study.
7. 9.     Subjects who have had subtotal or total colectomy or have a jejunostomy, ileostomy, colostomy, ileo-anal pouch, or known fixed stenosis of the intestine.
8. 11.  Subjects with a current diagnosis of indeterminate colitis.
9. 12.  Subjects with clinical features suggesting monogenic very early onset inflammatory bowel disease.
10. 10. The subject has other serious comorbidities that will limit his or her ability to complete the study.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The primary endpoint is clinical remission at Week 54, where 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. • Endoscopy subscore 0 to 1 (modified so that a score of 1 does not include friability)."

Secondary endpoints 15

1. ·       Clinical remission at Week 14, where a subject achieves clinical remission if he or she meets the definition described in the primary endpoint.
2. ·       Sustained clinical remission at Week 54, where a subject achieves sustained clinical remission if he or she achieved clinical remission (as defined by primary endpoint) at Week 14 and at Week 54.
3. ·       Sustained endoscopic remission, defined as MES of ≤1 point, at Week 14 and at Week 54
4. ·       Endoscopic response, defined as a decrease in MES ≥1 point at Week 14.
5. ·       Endoscopic response, defined as a decrease in MES ≥1 point at Week 54.
6. ·       Corticosteroid-free clinical remission at Week 54, where a subject achieves corticosteroid-free clinical remission at Week 54 if he or she meets the definition described in the primary endpoint and was off corticosteroids at least 12 weeks prior to and at Week 54.
7. ·       Clinical remission based on complete Mayo score at Week 54, where a subject achieves clinical remission if he or she achieved a complete Mayo score ≤2 points with no individual subscore >1 at Week 54.
8. ·       Serum trough concentrations of vedolizumab over time.
9. ·       Positive AVA and positive neutralizing AVA during the study.
10. ·       Sustained clinical response of subjects at Weeks 14 and 54, where a subject meets clinical response if he or she has a reduction in complete Mayo score (see Appendix G) 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.
11. ·       Clinical response at Weeks 2, 6, 10, 14, 22, 30, 38, 46, and 54 where a subject achieves clinical response if he or she meets the following definition: –      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.
12. ·       Clinical remission at Weeks 2, 6, 10, 14, 22, 30, 38, 46, and 54 where a subject achieves clinical remission based on partial Mayo score (a partial Mayo score of ≤2 points and no individual subscore >1 point).
13. ·       Safety assessments: descriptions of AEs; SAEs; and adverse events of special interest (AESIs), including evaluation of opportunistic infection, such as PML, liver injury, malignancies, infusion-related reactions, and hypersensitivity.
14. ·       Change from baseline in weight gain and linear growth z-score during the course of dosing with vedolizumab.
15. ·       Change in Tanner stage at Week 54 compared with baseline, each domain separately.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Auxiliary 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Takeda Development Center Americas Inc.

Sponsor organisation

Takeda Development Center Americas Inc.

Address

95 Hayden Avenue

City

Lexington

Postcode

02421-7942

Country

United States

Scientific contact point

Organisation

Takeda Development Center Americas Inc.

Contact name

Kellie Giles

Public contact point

Organisation

Takeda Development Center Americas Inc.

Contact name

Takeda

Third parties 9

Locations

6 EU/EEA countries · 25 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Summary of results Art. 37(4) CTR

Layperson summary Annex V

Documents 23 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications