A Study of Vedolizumab in Children and Teenagers With Moderate to Severe Crohn's Disease (CD)

Официальное название

A Randomized, Double-Blind, Phase 3 Study to Evaluate the Efficacy and Safety of Vedolizumab Intravenous as Maintenance Therapy in Pediatric Subjects With Moderately to Severely Active Crohn's Disease Who Achieved Clinical Response Following Open-Label Vedolizumab Intravenous Therapy

Обзор

Vedolizumab is a medicine that helps to reduce inflammation and pain in the digestive system. In this study, children and teenagers with moderate to severe Crohn's disease will be treated with vedolizumab. The main aim of the study is to check if participants achieve remission after treatment with the vedolizumab. Remission means symptoms improve or disappear and an endoscopy shows no signs of inflammation. Participants will receive 3 infusions of vedolizumab over 6 weeks. Then, those who have a clinical response will receive either a high dose or low dose of vedolizumab once every 8 weeks. They will receive the same dose every time.

Подробное описание

The drug being tested in this study is called vedolizumab. Vedolizumab is being tested to treat pediatric participants who have moderately to severely active CD. The drug is tested and approved in adults in approximately 70 countries. Participants to be enrolled must have failed response to, lost response to, or been intolerant to at least 1 of the current standard of care (SOC) induction and maintenance therapies for CD including exclusive and/or partial enteral nutrition therapy, immunomodulators (e.g., azathioprine \[AZA\], 6-mercaptopurine \[6-MP\], methotrexate \[MTX\]), and tumor necrosis factor-alpha (TNF-α) antagonists.

The study will enroll approximately 120 patients.

During the Induction Period participants will receive 3 doses of vedolizumab IV infusion at Day 1, Week 2, and Week 6 based on their weight at Baseline as:

* Participants 10 to 15 kg, Vedolizumab 150 mg * Participants \>15 to \<30 kg, Vedolizumab 200 mg * Participants ≥30 kg, Vedolizumab 300 mg

At Week 14, participants who achieve clinical response will be randomly assigned (by chance, like flipping a coin) in a 1:1 ratio to one of the 2 double-blind dose groups (high dose and low dose), stratified by previous exposure/failure to TNF-α antagonists therapy or naive to TNF-α antagonists therapy, and by weight groups. Participants will receive vedolizumab IV infusions every 8 weeks (Q8W) up to Week 46 during the Maintenance Period as follows:

* Participants ≥30 kg, Vedolizumab 300 mg (High dose) or 150 mg (Low dose) * Participants \>15 to \<30 kg, Vedolizumab 200 mg (High dose) 100 mg (Low dose) * Participants 10 to 15 kg, Vedolizumab 150 mg (High dose) or 100 mg (Low dose)

The dose will remain blinded to the participant and study doctor during the study (unless there is an urgent medical need). All participants will be administered vedolizumab via IV infusion. In participants who demonstrate lack of maintenance of clinical response during the Maintenance Period the dose will be escalated in a blinded fashion to the high dose in their weight group based on the weight at the time of the worsening of disease. In addition one-time rescue therapy with corticosteroids is allowed during Maintenance Period.

This multi-center trial will be conducted worldwide. After the Week 54, participants may be eligible to continue receiving vedolizumab in extension study MLN0002-3029. Participants who do not maintain corticosteroid-free clinical response at week 54 will undergo an end-of-study (EOS) or ET visit, and a safety visit 18 weeks after the last dose of vedolizumab followed by 2 years of long term follow-up (up to 104 weeks), in addition these participants will then be eligible to enter study MLN0002-3029 for an observational LTFU period of 2 years after the last dose of study drug.

Вмешательства

• Препарат Vedolizumab IV
  Vedolizumab IV

Первичные конечные точки

• Percentage of Participants With Clinical Remission at Week 54 Based on Pediatric Crohn's Disease Activity Index (PCDAI) Score ≤10 [Срок оценки: Week 54]
• Percentage of Participants With Endoscopic Response at Week 54 Based on Simple Endoscopic Score for Crohn's Disease [SES-CD] Score [Срок оценки: Week 54]

Вторичные конечные точки (12)

• Percentage of Participants with Clinical and Endoscopic Remission at Week 14 Based on Both PCDAI Score and SES-CD Score [Срок оценки: Week 14]
• Percentage of Participants with Clinical and Endoscopic Remission at Week 54 Based on Both PCDAI Score and SES-CD Score [Срок оценки: Week 54]
• Percentage of Participants with Sustained Clinical and Endoscopic Remission at Week 54 [Срок оценки: Week 54]
• Percentage of Participants with Corticosteroid-free Remission at Week 54 Based on PCDAI Score [Срок оценки: Week 54]
• Percentage of Participants with Sustained Endoscopic Remission Based on SES-CD Score [Срок оценки: Week 14]
• Percentage of Participants with Sustained Endoscopic Remission Based on SES-CD Score [Срок оценки: Week 54]
• Percentage of Participants with Sustained Clinical Remission at Week 14 Based on PCDAI Score [Срок оценки: Week 14]
• Percentage of Participants with Sustained Clinical Remission at Week 54 Based on PCDAI Score [Срок оценки: Week 54]
• Serum Trough Concentrations of Vedolizumab Over Time [Срок оценки: Predose and postdose at multiple time points (up to 54 weeks)]
• Percentage of Participants With Positive Antivedolizumab Antibodies [Срок оценки: Pre-dose (up to 54 weeks)]
• Percentage of Participants With Positive Neutralizing Antivedolizumab Antibody Titers [Срок оценки: Pre-dose (up to 54 weeks)]
• Sustained Clinical Response at Week 14 Based on PCDAI Score [Срок оценки: Week 14]

Критерии участия

Main Inclusion Criteria:

• The participants has moderately to severely active CD, unresponsive or intolerant to their current standard of care (SOC).
• The participants weigh ≥10 kg at the time of screening and enrollment into the study.
• Participants with Crohn's disease (CD) diagnosed at least 1 month before screening. Participants with moderately to severely active CD defined by a Pediatric Crohn's Disease Activity Index (PCDAI) >30 and an simple endoscopic score for Crohn's Disease (SES-CD) >6 (or an SES-CD ≥4 if disease is confined to terminal ileum) at screening endoscopy.
• Participants who have failed, lost response to, or been intolerant to treatment with at least 1 of the following agents: corticosteroids, immunomodulators (eg, azathioprine (AZA), 6-mercaptopurine (6-MP), methotrexate \[MTX\]), and/or tumor necrosis factor (TNF)-α antagonist therapy (eg, infliximab, adalimumab). This includes participants who are dependent on corticosteroids or exclusive or partial enteral nutrition to control symptoms and who are experiencing worsening of disease in the moderate-to-severe range when attempting to wean off corticosteroids or discontinue exclusive enteral nutrition.
• Participants 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.
• Participants with vaccinations that are up-to-date based on the countrywide accepted schedule of childhood vaccines.

Main Exclusion Criteria:

• Participants 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.
• Participants with 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.
• The participants had a clinically significant infection (eg, pneumonia, pyelonephritis, coronavirus disease 2019 \[COVID-19\]) within 30 days prior to first dose of study drug.
• The participants has received any live vaccinations within 30 days prior to first dose.
• Participants who currently require surgical intervention or are anticipated to require surgical intervention for CD during this study.
• Participants who have had subtotal or total colectomy or have a jejunostomy, ileostomy, colostomy, ileo-anal pouch, known fixed stenosis of the intestine, short bowel syndrome, or >3 small intestine resections.
• Participants with a current diagnosis of indeterminate colitis.
• Participants with clinical features suggesting monogenic very early-onset inflammatory bowel disease.
• 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.
• Participants with evidence of positive hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb). Hepatitis B virus (HBV) immune participants(i.e., 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.

• Participants with chronic hepatitis C virus (HCV) (ie, positive HCV antibody \[HCVAb\] and HCV RNA).

Note: Participants who are HCVAb-positive without evidence of HCV RNA may be considered eligible (spontaneous viral clearance or previously treated and cured \[defined as no evidence of HCV RNA at least 12 weeks before baseline\]).

• The participants has any identified congenital or acquired immunodeficiency (eg, common variable immunodeficiency, human immunodeficiency virus \[HIV\] infection, organ transplantation).
• The participant has evidence of dysplasia or history of malignancy other than a successfully treated non-metastatic cutaneous squamous cell or basal cell carcinoma or localized carcinoma in situ of the cervix.
• Participants with positive stool studies for ova and/or parasites or stool culture at screening visit.
• Participants with positive Clostridioides difficile (C difficile) stool test at screening visit.

Other inclusion/exclusion criteria may apply.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Четверное слепое

Основная цель

Лечение

Центры проведения

США · 22 центра

• Phoenix Childrens Hospital — Phoenix
• Cedars Sinai Medical Center — Los Angeles
• Rady Childrens Hospital San Diego - PIN — San Diego
• University of California San Francisco — San Francisco
• I.H.S Health LLC — Kissimmee
• Childrens Center For Digestive Healthcare — Atlanta
• Advocate Children's Hospital Park Ridge — Park Ridge
• Riley Hospital For Children — Indianapolis
• … и ещё 14 центров

Польша · 10 центров

• Uniwersytecki Szpital Dzieciecy — Krakow
• Uniwersytecki Szpital Kliniczny im. Jana Mikulicza Radeckiego we Wroclawiu — Wroclaw
• WIP Warsaw IBD Point Profesor Kierkus — Warsaw
• Instytut Pomnik Centrum Zdrowia Dziecka — Warsaw
• Korczowski Bartosz, Gabinet Lekarski — Rzeszów
• Copernicus Podmiot Leczniczy Sp. z o.o. — Gdansk
• Gornoslaskie Centrum Zdrowia Dziecka Im. Sw. Jana Pawla II Spsk Nr 6 Sum W Katowicach — Katowice
• Twoja Przychodnia SCM — Szczecin
• … и ещё 2 центра

Израиль · 7 центров

• Schneider Childrens Medical Center of Israel Petah Tikvah PIN — Petah Tikva
• Tel Aviv Sourasky Medical Center PPDS — Jerusalem
• Soroka University Medical Centre — Beersheba
• Rambam Medical Center - PPDS — Haifa
• Carmel Medical Center — Haifa
• Shaare Zedek Medical Center — Jerusalem
• Hadassah Medical Center - PPDS — Jerusalem

Италия · 6 центров

• AOU dell'Universita degli Studi della Campania Luigi Vanvitelli — Naples
• Azienda Ospedaliera Universitaria Federico II — Naples
• Azienda USL di Bologna — Bologna
• Sapienza University of Rome — Rome
• ASST di Monza - Azienda Ospedaliera San Gerardo — Monza
• Universita degli Studi di Padova — Padova

Великобритания · 6 центров

Список центров уточняется — проверьте первичный протокол.

Испания · 5 центров

Список центров уточняется — проверьте первичный протокол.

Австралия · 4 центра

• Children's Hospital at Westmead — Westmead
• Queensland Childrens Hospital — South Brisbane
• Monash Health, Monash Medical Centre — Clayton
• Royal Children's Hospital Melbourne - PIN — Parkville

Канада · 4 центра

• University of Alberta Hospital — Edmonton
• British Columbia Children's Hospital — Vancouver
• London Health Sciences Centre — London
• Centre Hospitalier Universitaire Sainte-Justine — Montreal

Китай · 4 центра

• Beijing Children Hospital,Capital Medical University — Пекин
• Henan Children's Hospital(Zhengzhou Children's Hospital) — Чжэнчжоу
• Children's Hospital of Fudan University — Шанхай
• The Children's Hospital Zhejiang UniversitySchool of Medicine — Ханчжоу

Греция · 4 центра

• Attikon University General Hospital — Athens
• Children's Hospital "Agia Sofia" — Athens
• Ippokratio General Hospital of Thessaloniki — Thessaloniki
• Ippokratio General Hospital of Thessaloniki — Thessaloniki

Япония · 4 центра

• Kurume University Hospital — Kurume-Shi
• Japanese Red Cross Kumamoto Hospital — Kumamoto
• Juntendo University Hospital — Bunkyo-Ku
• National Center for Child Health and Development — Setagaya-Ku

South Korea · 4 центра

Список центров уточняется — проверьте первичный протокол.

Бельгия · 3 центра

• UZ Antwerpen — Edegem
• Universitair Ziekenhuis Brussel - PIN — Jette
• UZ Leuven — Leuven

Хорватия · 3 центра

• Klinika Za Djecje Bolesti Zagreb — Zagreb
• University Hospital Center Zagreb — Zagreb
• University Hospital Centre Split — Split

Чехия · 3 центра

• Fakultni nemocnice Kralovske Vinohrady — Prague
• Fakultni Thomayerova Nemocnice — Prague
• Fakultni nemocnice Ostrava — Ostrava

Венгрия · 3 центра

• Borsod-Abauj-Zemplen Megyei Kozponti Korhaz es Egyetemi Oktato Korhaz — Miskolc
• Szegedi Tudomanyegyetem Szent-Gyorgyi Albert Klinikai Kozpont — Szeged
• Semmelweis Egyetem — Budapest

Литва · 2 центра

• Hospital of Lithuanian University of Health Sciences Kaunas Clinics — Kaunas
• Vilnius University Hospital Santaros Klinikos — Vilnius

Словакия · 2 центра

• Detska fakultna nemocnica s poliklinikou Banska Bystrica — Banská Bystrica
• … и ещё 1 центр

Идентификаторы

NCT: NCT04779320 · MLN0002-3025 · 2020-004301-31 · jRCT2071210031 · 2023-509045-13-00

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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