Efficacy and Safety of Vedolizumab Intravenous in Pediatric Chronic Pouchitis

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

1 Aug 2024 → ongoing

Decision date (initial)

2024-06-27

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Takeda Development Center Americas, Inc.

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy, Pharmacokinetic, Therapy

To assess the efficacy of vedolizumab IV in pediatric subjects with active chronic pouchitis in terms of the proportion of subjects who achieve clinical remission at Week 14.

Secondary objectives 1

1. "To evaluate the efficacy of vedolizumab IV in pediatric subjects with active chronic pouchitis by: The proportion of subjects achieving clinical (mPDAI) remission evaluated at Week 34. The proportion of subjects achieving PDAI remission evaluated separately at Week 14 and Week 34. The proportion of subjects achieving clincal response evaluated seperately at Week 14 and Week 34. Change from baseline in mPDAI score total at Week 14 and Week 34. Change from baseline in PDAI total score and PDAI clinical symptoms, endoscopic and histology subscores at Week 14 and Week 34. Change from baseline in age-appropriate health related quality of life measured by EQ-5D-Y Proxy Version 1.0 at Week 14 and Week 34. "

Conditions and MedDRA coding

Active Chronic Pouchitis

Study design 2 periods

Regulatory references

EMA paediatric investigation plan (PIP)

EMEA-000645-PIP04-20, 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 8

1. In the opinion of the investigator, the subject, parent, or legal guardian is capable of understanding and complying with protocol requirements.
2. The subject, parent or legal guardian has signed and dated a written, informed consent form and subject assent form and any required privacy authorization before the initiation of any study procedures.
3. The subject is aged 2 to 17 years, inclusive, at the time of screening and first dose.
4. The subject weighs ≥10 kg at the time of screening and first dose.
5. The subject has a history of proctocolectomy and IPAA as treatment for ulcerative colitis (UC), Crohn’s disease (CD), familial adenomatous polyposis, or other underlying conditions, such as Hirschsprung's disease, for which construction of a puch was medically indicated, completed at least 1 year before the screening visit.
6. "The subject has active chronic pouchitis, defined by an mPDAI score ≥5 assessed using the average of subject-reported clinical symptoms from 3 days during a 5-day period immediately before screening endoscopy (ie, video pouchoscopy with biopsy) or bowel preparation for endoscopy, and a minimum mPDAI endoscopic subscore of 2 (outside the staple or suture line) and either: a) Has had ≥1 previous episodes of pouchitis within 1 year before the screening visit, with symptoms lasting at least 4 weeks, treated with ≥2 weeks of antibiotic or otherprescription therapy (ie, other antibiotics, probiotics, immunomodulators, or anti-TNFs within 1 year before screening). or b) Has had an inadequate response with, or lost response to, or is intolerant to antibiotic therapy (ie, requiring maintenance antibiotic therapy taken continuously for ≥4 weeks immediately before the baseline endoscopy visit or not able to receive or continue antibiotic treatment due to intolerance or other contraindication)."
7. "A male subject who is sexually active with a female partner of childbearing potential agrees to use a barrier method of contraception (ie, condom with spermicide)* from signing of parental informed consent/subject assent throughout the duration of the study and for 18 weeks after last dose. The female partner of a male subject should also be advised to use a highly effective method of contraception."
8. A female subject of childbearing potential who is sexually active with a male partner agrees to use a highly effective method of contraception* from signing of parental informed consent/subject assent throughout the duration of the study and for 18 weeks after last dose.

Exclusion criteria 8

1. The subject has symptoms believed to be predominantly due to irritable pouch syndrome.
2. The subject has isolated cuffitis.
3. The subject is found to have dysplasia at the screening endoscopy.
4. The subject has any prior exposure to approved or investigational anti-integrins including, but not limited to natalizumab, efalizumab, etrolizumab, or AMG 181, or mucosal addressin cell adhesion molecule-1 (MAdCAM-1) antagonists, or rituximab as a treatment for pouchitis.
5. The subject has received either (1) an investigational biologic agent (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 for inflammatory bowel disease within 2 weeks before the first dose of study drug or at any time during the screening period
6. The subject has mechanical complications of the pouch (ie, pouch stricture or pouch fistula).
7. The subject has a diverting stoma.
8. The subject currently requires or has a planned surgical intervention during the study.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. 01. The primary efficacy endpoint is clinical (mPDAI) remission (defined as an mPDAI score <5 and a reduction of overall mPDAI score by ≥2 points from baseline) assessed at W14.

Secondary endpoints 10

1. 01.Clinical (mPDAI) remission (defined as an mPDAI score <5 and a reduction of overall mPDAI score by ≥2 points from baseline) assessed at W34.
2. 02. PDAI remission (defined as PDAI score <7 and a decrease in PDAI score by ≥3 points from baseline) at W14.
3. 03. PDAI remisssion (defined as PDAI score <7 and a decrease in PDAI score by >3 points from baseline) at W34
4. 04. Clinical (mPDAI) response (defined as a decrease in mPDAI score by ≥2 points from baseline) at W14
5. 05. Clinical (mPDAI) response (defined as a decrease in mPDAI score by >2 points fom baseline) at W34.
6. 06. Change from baseline in mPDAI clinical symptom subscore at W14.
7. 07. Change from baseline in mPDAI total score at W34
8. 08. Change from baseline in PDAI total score and PDAI clinical symptoms, endoscopic, and histologic subscores at W14
9. 09. Change from baseline in PDAI total score and PDAI clinical symptoms, endoscopic and histologic subscores at W34.
10. 10. Index scores, visual analogue scale (VAS), and changes from baseline for each in the EQ-5D-Y Proxy Version 1.0 at W14 and W34.

Investigational products

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

Test 1

Auxiliary 5

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Takeda Development Center Americas Inc.

Sponsor organisation

Takeda Development Center Americas Inc.

Address

500 Kendall Street

City

Cambridge

Postcode

02142-1108

Country

United States

Scientific contact point

Organisation

Takeda Development Center Americas Inc.

Contact name

Nerissa K. Velazco

Public contact point

Organisation

Takeda Development Center Americas Inc.

Contact name

Takeda

Third parties 9

Locations

8 EU/EEA countries · 14 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

Documents 169 files

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

Application history

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