Clinical trial NCT06443502: A Study to Learn About the Safety of Vedolizumab and How Well it Works in Children and Teenagers With Active Chronic Pouchitis
Official title: An Open-label Single-Arm Phase 3 Study to Evaluate the Efficacy, Safety, Tolerability, Pharmacokinetics, and Immunogenicity of Vedolizumab Intravenous in the Treatment of Pediatric Subjects With Active Chronic Pouchitis
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Pouchitis
Keywords: Drug Therapy
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2024-06-05
Enrollment: 30
Sex: ALL
Minimum age (years): 2
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: When some people have their large bowel removed, a surgeon can make a "pouch" from part of the small bowel to connect it to the back passage (anus). Pouchitis is when the pouch becomes inflamed (swollen) or infected. The main aim of this study is to find out if vedolizumab improves pouchitis symptoms and pouch inflammation. Other aims include to find out if vedolizumab is well tolerated and if it causes any medical problems (adverse events or side effects) and to look for any changes in the well-being of participants during their treatment with vedolizumab.

This study consists of two parts: Part 1 includes the induction and maintenance periods, and Part 2 includes the continued maintenance period. Participants will receive up to 12 infusions of vedolizumab. In Part 1 of the study, first 3 infusions are in first 6 weeks (Day 1, Week 2 and Week 6). Participants who are getting benefit may continue with the treatment for up to 7.5 months (30 weeks) in the maintenance period for Part 1. After completing treatment with vedolizumab in Part 1, participants will visit their clinic for a health check at Week 34.

Participants who show clinical response at Week 34 will continue to Part 2, receiving vedolizumab every 8 weeks for an additional 40 weeks, starting at Week 38 and ending with the last dose being at Week 78. Final efficacy assessments, including a pouchoscopy will be performed at Week 82.

Detailed description: The drug being tested in this study is called vedolizumab. This study will look at the efficacy, safety, tolerability, pharmacokinetics (PK), and immunogenicity of vedolizumab in pediatric participants with active chronic pouchitis.

The study will enroll approximately 30 participants. All the participants will be enrolled in a single treatment group to receive treatment with vedolizumab based on participant's weight mentioned as follows:

* Participants with body weight greater than or equal to (\>=) 30 kilogram (kg) will receive vedolizumab, high dose
* Participants with body weight greater than (\>) 15 to less than (\<) 30 kg will receive vedolizumab, medium dose
* Participants with body weight 10 to 15 kg will receive vedolizumab, low dose

All participants will receive vedolizumab intravenous infusion at Day 1, and at Weeks 2, 6, 14, 22, and 30. Participants will also receive concomitant antibiotic treatment (ciprofloxacin, metronidazole, or other antibiotics) from Day 1 through Week 2. Participants with clinical response at the end of Part 1 maintenance at Week 34 will continue to Part 2 of the study and will receive vedolizumab intravenous infusion every 8 weeks from Week 38 through Week 78.

This multi-center trial will be conducted globally. The maximum overall duration of the study is up to approximately 2 years. Participants will be followed up for 18 weeks after the last dose of the study drug for safety.

Eligibility criteria: Inclusion Criteria:

1. The participant weighs \>=10 kg at the time of screening and first dose.
2. Has active chronic pouchitis, defined by a mPDAI score \>=5 assessed using the 3-day average of participant-reported clinical symptoms prior to the screening endoscopy (that is \[ie\] video pouchoscopy with biopsy) or bowel preparation for the endoscopy and a minimum mPDAI endoscopic subscore of 2 (outside the staple or suture line) and either:

   * \>=1 previous episodes of pouchitis within 1 year before the screening visit, with symptoms lasting for at least a total of 4 weeks, treated with \>=2 weeks of antibiotic or other prescription therapy (ie, other antibiotics, probiotics, immunomodulators, or anti-tumor necrosis factor \[TNFs\] within 1 year before screening). Or
   * Have had an inadequate response with, or lost response to, or be intolerant to antibiotic therapy (ie, requiring maintenance antibiotic therapy taken for \>=4 weeks immediately before the baseline endoscopy visit or not able to receive or continue antibiotic treatment due to intolerance or other contraindication).
3. The participant is aged 2 to 17 years, inclusive, at the time of screening and first dose.
4. The participant has a history of proctocolectomy and ileal pouch-anal anastomosis (IPAA) as treatment for ulcerative colitis (UC), Crohn's disease (CD), familial adenomatous polyposis (FAP), or other underlying conditions, such as Hirschsprung's disease, for which construction of a pouch was medically indicated, completed at least 1 year before the screening visit.

Exclusion Criteria:

The exclusion criteria are divided into 3 categories: active chronic pouchitis exclusion criteria, infectious disease exclusion criteria, and general exclusion criteria.

Active Pouchitis Exclusion Criteria:

1. Has symptoms believed to be predominantly due to irritable pouch syndrome.
2. Has isolated cuffitis.
3. Is found to have dysplasia at the screening endoscopy.
4. Has mechanical complications of the pouch (for example \[e.g.\] pouch stricture or pouch fistula).
5. Currently requires or has a planned surgical intervention during the study.
6. Has a diverting stoma.

   Infectious Disease Exclusion Criteria:
7. Has evidence of an active infection (e.g. sepsis, cytomegalovirus \[CMV\], or listeriosis) during screening.
8. Had a clinically significant infection (e.g. pneumonia, pyelonephritis, coronavirus disease 2019 \[COVID-19\]) within 35 days before first dose of study drug.
9. Has active or latent tuberculosis (TB), as evidenced by a diagnostic TB test performed within 3 months of screening or during the screening period that is positive, as defined by:

   * A positive QuantiFERON test or 2 successive indeterminate QuantiFERON tests, or
   * A TB skin test reaction \>=5 millimeter (mm). NOTE: If participant have received Bacillus Calmette-Guérin vaccine, then a QuantiFERON TB Gold test should be performed instead of the TB skin test.

   NOTE: Participants with documented previously treated TB with a negative QuantiFERON test can be included in the study.
10. Has evidence of positive hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb). Hepatitis B virus (HBV) immune participants (e.g. 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.
11. Has chronic hepatitis C virus (HCV) (ie, positive HCV antibody \[HCVAb\] and HCV Ribonucleic Acid \[RNA\]).

    NOTE: Participants who are HCVAb-positive without evidence of HCV RNA may be considered eligible (spontaneous viral clearance or previously treated and cured \[defined as no evidence of HCV RNA at least 12 weeks before baseline\]).
12. Has any identified congenital or acquired immunodeficiency (e.g. common variable immunodeficiency, HIV infection, organ transplantation).
13. Has positive stool studies for ova and/or parasites or stool culture at screening visit.
14. Has positive Clostridium difficile stool test at screening visit.

    General Exclusion Criteria:
15. Is taking, has taken, or is required to take any excluded medications.
16. 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.
17. 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.
18. Has any unstable or uncontrolled cardiovascular, pulmonary, hepatic, renal, GI, genitourinary, hematologic, coagulation, immunological, endocrine/metabolic, neurologic, or other medical disorder that, in the opinion of the investigator, would confound the study results or compromise participant safety.

Primary outcomes:
measure: Percentage of Participants Achieving Clinical Modified Pouchitis Disease Activity Index (mPDAI) Remission at Week 14
timeFrame: At Week 14
Secondary outcomes:
measure: Percentage of Participants Achieving Clinical (mPDAI) Remission at Week 34
timeFrame: At Week 34
measure: Percentage of Participants Achieving Pouchitis Disease Activity Index (PDAI) Remission at Week 14
timeFrame: At Week 14
measure: Percentage of Participants Achieving PDAI Remission at Week 34
timeFrame: At Week 34
measure: Percentage of Participants Achieving Clinical (mPDAI) Response at Week 14
timeFrame: At Week 14
measure: Percentage of Participants Achieving Clinical (mPDAI) Response at Week 34
timeFrame: At Week 34
measure: Change From Baseline in (mPDAI) Total Score at Week 14
timeFrame: Baseline, Week 14
measure: Change From Baseline in (mPDAI) Total Score at Week 34
timeFrame: Baseline, Week 34
measure: Change From Baseline in PDAI Total Score at Week 14
timeFrame: Baseline, Week 14
measure: Change From Baseline in PDAI Total Score at Week 34
timeFrame: Baseline, Week 34
measure: Change From Baseline in PDAI Clinical Symptoms Subscore at Week 14
timeFrame: Baseline, Week 14
measure: Change From Baseline in PDAI Clinical Symptoms Subscore at Week 34
timeFrame: Baseline, Week 34
measure: Change From Baseline in PDAI Endoscopic Subscore at Week 14
timeFrame: Baseline, Week 14
measure: Change From Baseline in PDAI Endoscopic Subscore at Week 34
timeFrame: Baseline, Week 34
measure: Change From Baseline in PDAI Acute Histologic Inflammation Subscore at Week 14
timeFrame: Baseline, Week 14
measure: Change From Baseline in PDAI Acute Histologic Inflammation Subscore at Week 34
timeFrame: Baseline, Week 34
measure: EuroQol- 5 Dimension for Youth (EQ-5D-Y) Index Scores and Visual Analogue Scale (VAS) at Week 14
timeFrame: At Week 14
measure: EQ-5D-Y Index Scores and VAS at Week 34
timeFrame: At Week 34
measure: Change From Baseline in the EQ-5D-Y Index Scores and VAS at Week 14
timeFrame: Baseline, Week 14
measure: Change From Baseline in the EQ-5D-Y Index Scores and VAS at Week 34
timeFrame: Baseline, Week 34
Other outcomes:
Locations:
city: Leuven
country: Belgium
facility: UZ Leuven
state: Vlaams Brabant
city: Zagreb
country: Croatia
facility: Klinika Za Djecje Bolesti Zagreb
state: Grad Zagreb
city: Praha
country: Czechia
facility: Fakultni nemocnice v Motole
city: Athens
country: Greece
facility: General Hospital of Diseases Thoracos of Athens "Sotiria"
state: Attiki
city: Jerusalem
country: Israel
facility: Shaare Zedek Medical Center
state: Yerushalayim
city: Petach Tikvah
country: Israel
facility: Schneider Childrens Medical Center of Israel Petah Tikvah PIN
city: Napoli
country: Italy
facility: AOU dell'Universita degli Studi della Campania Luigi Vanvitelli - Piazza Luigi Miraglia, 2
state: Campania
city: Trieste
country: Italy
facility: IRCCS Materno Infantile Burlo Garofolo - INCIPIT - PIN
state: Friuli-Venezia Giulia
city: Roma
country: Italy
facility: AOU Policlinico Umberto I-Viale Regina Elena, 324
state: Lazio
city: Roma
country: Italy
facility: IRCCS Ospedale Pediatrico Bambino Gesu - INCIPIT - PIN
state: Lazio
city: Genova
country: Italy
facility: Istituto G Gaslini Ospedale Pediatrico IRCCS - INCIPIT - PIN
state: Liguria
city: Messina
country: Italy
facility: Az Ospedaliera Universitaria Policlinico G Martino
state: Sicilia
city: Warszawa
country: Poland
facility: Instytut Pomnik Centrum Zdrowia Dziecka
state: Mazowieckie
city: Krakow
country: Poland
facility: Collegium Medicum Uniwersytetu Jagiellonskiego
city: Esplugues de Llobregat
country: Spain
facility: Hospital Sant Joan de Deu - PIN
state: Barcelona
city: Valencia
country: Spain
facility: Hospital Universitari i Politecnic La Fe de Valencia
Study officials:
affiliation: Takeda
name: Study Director
role: STUDY_DIRECTOR
References: