A Study to Learn About the Safety of Vedolizumab and How Well it Works in Children and Teenagers With Active Chronic Pouchitis

Pouchitis Clinical Trial

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06443502
• Other study ID #: Vedolizumab-3041
• Secondary ID: 2023-504773-20
• Status: Not yet recruiting
• Phase: Phase 3
• Start date: June 25, 2024
• Est. completion date: December 31, 2029

Study information

• Verified date: May 2024
• Source: Takeda
• Contact: Takeda Contact
• Phone: +1-877-825-3327
• Email: medinfoUS[@]takeda.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Participants will receive up to 6 infusions of vedolizumab. 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 total. After completing treatment with vedolizumab, participants will visit their clinic for a health check at Week 34. One final health check will be scheduled 4.5 months (18 weeks) after the last vedolizumab infusion.

Participants who continue to benefit from their treatment at the end of this study will be invited to continue treatment with vedolizumab in another clinical study (Vedolizumab-3042).

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 along with ciprofloxacin, metronidazole, or other antibiotics 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, Weeks 2, 6, 14, 22, and 30 along with concomitant antibiotic treatment from Day 1 through Week 2.

This multi-center trial will be conducted globally. The overall duration of the study is up to 57 weeks. Participants will be followed up for 18 weeks after the last dose of the study drug for safety.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 30
• Est. completion date: December 31, 2029
• Est. primary completion date: December 31, 2029
• Accepts healthy volunteers: No
• Gender: All
• Age group: 2 Years to 17 Years

Eligibility

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:

• 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 other prescription therapy (ie, other antibiotics, probiotics, immunomodulators, or anti-tumor necrosis factor [TNFs] within 1 year before screening). Or

• Has had an inadequate response with, or lost response to, or are 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).

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.

Related Conditions & MeSH terms

• Pouchitis

Intervention

Drug:
• Vedolizumab
Vedolizumab intravenous infusion.
• Concomitant Antibiotic Therapy
Ciprofloxacin, metronidazole, vancomycin, amoxicillin clavulanate or rifaximin.

Locations

Country	Name	City	State
Belgium	UZ Leuven	Leuven	Vlaams Brabant
Croatia	Klinika Za Djecje Bolesti Zagreb	Zagreb	Grad Zagreb
Czechia	Fakultni nemocnice v Motole	Praha
Greece	General Hospital of Diseases Thoracos of Athens "Sotiria"	Athens	Attiki
Israel	Shaare Zedek Medical Center	Jerusalem	Yerushalayim
Israel	Schneider Childrens Medical Center of Israel Petah Tikvah PIN	Petach Tikvah
Italy	Istituto G Gaslini Ospedale Pediatrico IRCCS - INCIPIT - PIN	Genova	Liguria
Italy	Az Ospedaliera Universitaria Policlinico G Martino	Messina	Sicilia
Italy	AOU dell'Universita degli Studi della Campania Luigi Vanvitelli - Piazza Luigi Miraglia, 2	Napoli	Campania
Italy	AOU Policlinico Umberto I-Viale Regina Elena, 324	Roma	Lazio
Italy	IRCCS Ospedale Pediatrico Bambino Gesu - INCIPIT - PIN	Roma	Lazio
Italy	IRCCS Materno Infantile Burlo Garofolo - INCIPIT - PIN	Trieste	Friuli-Venezia Giulia
Poland	Collegium Medicum Uniwersytetu Jagiellonskiego	Krakow
Poland	Instytut Pomnik Centrum Zdrowia Dziecka	Warszawa	Mazowieckie
Spain	Hospital Sant Joan de Deu - PIN	Esplugues de Llobregat	Barcelona
Spain	Hospital Universitari i Politecnic La Fe de Valencia	Valencia

Sponsors (1)

Lead Sponsor	Collaborator
Takeda

Countries where clinical trial is conducted

Belgium,  Croatia,  Czechia,  Greece,  Israel,  Italy,  Poland,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants Achieving Clinical Modified Pouchitis Disease Activity Index (mPDAI) Remission at Week 14	Clinical (mPDAI) remission is defined as mPDAI score <5 and a reduction of mPDAI score by >=2 points from Baseline. The mPDAI score is calculated as a sum of two subscales based on clinical symptoms (0 to 6) and endoscopic findings (0 to 6): 1) Clinical Symptoms: Stool Frequency (0=usual postoperative stool frequency to 2=three or more stools/day>postoperative usual); Rectal bleeding (0=None or rare to 1=Present daily); Fecal urgency or abdominal cramps (0=None to 2=Usual), Fever (temperature >37.8 degrees celsius [C]) (0=Absent and 1=Present); 2) Endoscopic Inflammation Findings: Edema (0=not present to 1=present); Granularity (0=not present to 1=present); Friability (0=not present to 1=present); Loss of vascular pattern (0=not present to 1=present); Mucous exudates (0=not present to 1=present); Ulcerations (0=not present to 1=present). The total mPDAI score can range from 0 to 12. A higher mPDAI score is indicative of worse disease.	At Week 14
Secondary	Percentage of Participants Achieving Clinical (mPDAI) Remission at Week 34	Clinical (mPDAI) remission is defined as mPDAI score <5 and a reduction of mPDAI score by >=2 points from Baseline. The mPDAI score is calculated as a sum of two subscales based on clinical symptoms (0 to 6) and endoscopic findings (0 to 6): 1) Clinical Symptoms: Stool Frequency (0=usual postoperative stool frequency to 2=three or more stools/day>postoperative usual); Rectal bleeding (0=None or rare to 1=Present daily); Fecal urgency or abdominal cramps (0=None to 2=Usual), Fever (temperature >37.8 degrees C) (0=Absent and 1=Present); 2) Endoscopic Inflammation Findings: Edema (0=not present to 1=present); Granularity (0=not present to 1=present); Friability (0=not present to 1=present); Loss of vascular pattern (0=not present to 1=present); Mucous exudates (0=not present to 1=present); Ulcerations (0=not present to 1=present). The total mPDAI score can range from 0 to 12. A higher mPDAI score is indicative of worse disease.	At Week 34
Secondary	Percentage of Participants Achieving Pouchitis Disease Activity Index (PDAI) Remission at Weeks 14 and 34	PDAI remission is PDAI score <7 and reduction of score by >=3 points from Baseline. PDAI score calculated as sum of 3 subscales based on clinical symptoms (0-6), endoscopic findings (EF) (0-6), and histologic changes (0-6): 1)Clinical Symptoms: Stool Frequency (0=usual to postoperative stool frequency to 2=3 or more stools/day>postoperative usual); Rectal bleeding (0=None or rare,1=Present daily); Fecal urgency or abdominal cramps (0=None, 2=Usual),Fever (temperature>37.8 degree C) (0=Absent,1=Present);2) EF Findings: Edema (0=not present, 1=present);Granularity (0=not present, 1=present); Friability (0=not present,1=present);Loss of vascular pattern (0=not present, 1=present); Mucous exudates (0=not present, 1=present);Ulcerations (0=not present,1=present);3) Acute Histologic Inflammation: Polymorphic nuclear leukocyte infiltration (0=None, 3=Severe+crypt abscess); Ulceration per low power field (mean) (0=0% to 3=>50%). Total PDAI score ranges 0-18. Higher score means worse disease.	At Weeks 14 and 34
Secondary	Percentage of Participants Achieving Clinical (mPDAI) Response at Weeks 14 and 34	Clinical (mPDAI) response is defined as a reduction in mPDAI score by >=2 points from baseline. The mPDAI score is calculated as a sum of two subscales based on clinical symptoms (0 to 6) and endoscopic findings (0 to 6): 1) Clinical Symptoms: Stool Frequency (0=usual postoperative stool frequency to 2=three or more stools/day>postoperative usual); Rectal bleeding (0=None or rare to 1=Present daily); Fecal urgency or abdominal cramps (0=None to 2=Usual), Fever (temperature >37.8 degrees C) (0=Absent and 1=Present); 2) Endoscopic Inflammation Findings: Edema (0=not present to 1=present); Granularity (0=not present to 1=present); Friability (0=not present to 1=present); Loss of vascular pattern (0=not present to 1=present); Mucous exudates (0=not present to 1=present); Ulcerations (0=not present to 1=present). The total mPDAI score can range from 0 to 12. A higher mPDAI score is indicative of worse disease.	At Weeks 14 and 34
Secondary	Change From Baseline in Total (mPDAI) Score at Weeks 14 and 34	The mPDAI score is calculated as a sum of two subscales based on clinical symptoms (0 to 6) and endoscopic findings (0 to 6): 1) Clinical Symptoms: Stool Frequency (0=usual postoperative stool frequency to 2=three or more stools/day>postoperative usual); Rectal bleeding (0=None or rare to 1=Present daily); Fecal urgency or abdominal cramps (0=None to 2=Usual), Fever (temperature >37.8 degrees C) (0=Absent and 1=Present); 2) Endoscopic Inflammation Findings: Edema (0=not present to 1=present); Granularity (0=not present to 1=present); Friability (0=not present to 1=present); Loss of vascular pattern (0=not present to 1=present); Mucous exudates (0=not present to 1=present); Ulcerations (0=not present to 1=present). The total mPDAI score can range from 0 to 12. A higher mPDAI score is indicative of worse disease.	Baseline, Weeks 14 and 34
Secondary	Change From Baseline in Total PDAI Score at Weeks 14 and 34	The PDAI score calculated as sum of 3 subscales based on clinical symptoms (0-6), endoscopic findings (0-6), and histologic changes (0-6): 1)Clinical Symptoms: Stool Frequency (0=usual to postoperative stool frequency to 2=3 or more stools/day>postoperative usual); Rectal bleeding (0=None or rare,1=Present daily); Fecal urgency or abdominal cramps (0=None, 2=Usual),Fever (temperature>37.8 degree C) (0=Absent,1=Present); 2) Endoscopic Findings: Edema (0=not present, 1=present);Granularity (0=not present, 1=present); Friability (0=not present,1=present);Loss of vascular pattern (0=not present, 1=present); Mucous exudates (0=not present, 1=present);Ulcerations (0=not present,1=present);3) Acute Histologic Inflammation: Polymorphic nuclear leukocyte infiltration (0=None, 3=Severe + crypt abscess); Ulceration per low power field (mean) (0=0 percentage [%] to 3=>50%). Total PDAI score ranges 0-18. Higher score means worse disease.	Baseline, Weeks 14 and 34
Secondary	Change From Baseline in PDAI Clinical Symptoms Subscore at Weeks 14 and 34	The PDAI Clinical Symptoms subscore is a sum of scores (0 to 6) from findings for stool frequency (0=usual to postoperative stool frequency to 2=3 or more stools/day>postoperative usual); Rectal bleeding (0=None or rare to 1=Present daily); Fecal urgency or abdominal cramps (0=None to 2=Usual), Fever (temperature>37.8 degree C) (0=Absent to 1=Present). Higher scores are indicative of worse disease.	Baseline, Weeks 14 and 34
Secondary	Change From Baseline in PDAI Endoscopic Subscore at Weeks 14 and 34	The PDAI Endoscopic Inflammation subscore is a sum of scores (0 to 6) from findings for Edema (0=not present to 1=present); Granularity (0=not present to 1=present); Friability (0=not present to 1=present); Loss of vascular pattern (0=not present to 1=present); Mucous exudates (0=not present to 1=present); Ulcerations (0=not present to 1=present). Higher scores are indicative of worse disease.	Baseline, Weeks 14 and 34
Secondary	Change From Baseline in PDAI Acute Histologic Inflammation Subscore at Weeks 14 and 34	The PDAI Acute Histologic Inflammation subscore is a sum score (0 to 6) from findings for Polymorphic nuclear leukocyte infiltration (0=None to 3=Severe + crypt abscess); Ulceration per low power field (mean) (0=0% to 3=>50%). Higher scores are indicative of worse disease.	Baseline, Weeks 14 and 34
Secondary	EuroQol- 5 Dimension for Youth (EQ-5D-Y) Total Scores at Weeks 14 and 34	The EQ-5D-Y (Proxy Version 1.1) is composed of two sections. The first section contains one question for each of the five dimensions: mobility, looking after myself, doing usual activities, having pain or discomfort, and feeling worried, sad, or unhappy. Participants select from three response levels (no problems, some problems, a lot of problems) for each dimension. A health state profile score can be calculated from the responses on these five dimensions. The index score ranges from 0 (0 indicating a health state equivalent to death) to 1 (indicating full health). Higher scores demonstrate higher health utility. The second section includes a visual analogue scale (EuroQol [EQ] visual analogue scale). The scale is scored from 0 (the worst) to 100 (the best imaginable health). The reference to a high score indicates a better outcome of quality of life.	At Weeks 14 and 34
Secondary	Change From Baseline in the EQ-5D-Y Scores at Weeks 14 and 34	The EQ-5D-Y (Proxy Version 1.1) is composed of two sections. The first section contains one question for each of the five dimensions: mobility, looking after myself, doing usual activities, having pain or discomfort, and feeling worried, sad, or unhappy. Participants select from three response levels (no problems, some problems, a lot of problems) for each dimension. A health state profile score can be calculated from the responses on these five dimensions. The index score ranges from 0 (0 indicating a health state equivalent to death) to 1 (indicating full health). Higher scores demonstrate higher health utility. The second section includes a visual analogue scale (EQ visual analogue scale). The scale is scored from 0 (the worst) to 100 (the best imaginable health). The reference to a high score indicates a better outcome of quality of life.	Baseline, Weeks 14 and 34