A 52-week Study of Rilzabrutinib Efficacy and Safety Compared to Placebo in Adults Diagnosed With IgG4-related Disease

Официальное название

A Randomized, Phase 3, Double-blind, 52-week Study to Evaluate the Efficacy and Safety of Rilzabrutinib (SAR444671) Compared to Placebo in Adult Participants With Active IgG4-related Disease

Обзор

This is a Phase 3, parallel group, 2-arm, randomized, double blind, placebo-controlled, 52-week treatment study to assess the efficacy and safety of rilzabrutinib as a treatment for adult patients with active IgG4-RD. The purpose of this study is to measure time to adjudicated IgG4-RD clinical disease flare, and other relevant efficacy endpoints including flare-free rate, control of IgG4-RD disease activity, use of GC rescue and safety parameters such as treatment-emergent adverse events, clinical laboratory values and electrocardiograms (ECG) in participants aged 18 years and above, diagnosed with IgG4-RD and treated with rilzabrutinib tablets over a 52-week placebo-controlled period. Study details include: The study duration will be up to 60 weeks, including a Screening period of 4 to 6 weeks, a 52-week double blind treatment period, and 2 weeks of follow up (plus an optional OLE of 108 weeks). The number of visits will be 16 (plus an optional 9 visits during the OLE).

Вмешательства

• Препарат Rilzabrutinib
  Pharmaceutical form:Tablet-Route of administration:Oral
• Препарат Placebo
  Pharmaceutical form:Tablet-Route of administration:Oral
• Препарат Glucocorticoid
  Pharmaceutical form:Tablet, solution, suspension formulations according to local standard practices-Route of administration:Oral

Первичные конечные точки

• Time to first adjudicated clinical disease flare treated by the investigator during the Blinded Treatment period [Срок оценки: Until Week 52]

Вторичные конечные точки (12)

• Proportion of participants without IgG4-RD adjudicated clinical disease flare and off glucocorticoids and immunomodulators [Срок оценки: At Week 52]
• Proportion of participants without IgG4-RD adjudicated clinical disease flare and off glucocorticoids [Срок оценки: At Week 52]
• Annualized rate of clinical disease flares [Срок оценки: At Week 52]
• Change in IgG4-RD RI total activity scores from baseline to Week 52 [Срок оценки: From baseline to Week 52]
• Proportion of participants in complete remission at Week 52 [Срок оценки: At Week 52]
• Percent change in IgG4-RD RI total activity scores from baseline to Week 52 [Срок оценки: From baseline to Week 52]
• Change in IgG4-RD RI total activity scores from baseline to Week 12 [Срок оценки: From baseline to Week 12]
• Percent change in IgG4-RD RI total activity scores from baseline at Week 12 [Срок оценки: From baseline to Week 12]
• Proportion of participants with reduction of ≥2 points from the baseline IgG4-RD RI total activity score [Срок оценки: At Week 12, Week 24, and Week 52]
• Cumulative glucocorticoid dose for treatment of IgG4-RD [Срок оценки: At Week 52]
• Proportion of participants with potentially clinically significant abnormalities in laboratory tests, vital signs, and electrocardiograms in the Safety Population [Срок оценки: Until Week 160]
• Proportion of participants with TEAEs, AESIs, SAEs in the Safety Population [Срок оценки: Until Week 160]

Критерии участия

Критерии включения

• Participants must have a clinical diagnosis of IgG4-RD confirmed by the Adjudication Committee.
• Participants meeting Step 1 Entry criteria of 2019 ACR/EULAR classification criteria for IgG4-RD and Total inclusion points are ≥20
• Participants with active disease in at least 1 organ system, excluding lymph nodes, with active disease defined by an IgG4-RD Responder Index organ/site activity score ≥2 based on the manifestations of disease activity in the last 28 days.
• Participants with history or current involvement of at least 1 organ/site (excluding lymph nodes) affected with IgG4-RD.
• Participants with active IgG4-RD controlled for at least 2 weeks while on a stable dose of GC.
• Participants willing to taper off GC after starting IMP.
• Participants willing and able to participate in repeated study protocol mandated or clinically indicated imaging procedures to assess IgG4-RD such as computed tomography (CT), magnetic resonance imaging (MRI), positron emission tomography (PET), or ultrasound.
• Participants who have an up-to-date vaccination status as per local guidelines. The last dose of live vaccines should be received at least 30 days before Day 1.
• Contraceptive use by men and women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.

Критерии исключения

• Meet any Step 2 Exclusion criteria from the 2019 ACR/EULAR classification criteria for IgG4-RD.
• History of retroperitoneal fibrosis, sclerosing mesenteritis, fibrosing mediastinitis, or other overwhelmingly fibrotic expression of IgG4-RD that is the sole disease manifestation.
• Active malignancy or history of malignancy within 5 years before Day 1, except completely treated in situ carcinoma of the cervix, completely treated, and resolved nonmetastatic squamous or basal cell carcinoma of the skin.
• Known or suspected immunodeficiency, including history of invasive opportunistic infections (eg, histoplasmosis, listeriosis, coccidioidomycosis, pneumocystosis, and aspergillosis) despite infection resolution, or otherwise recurrent infections of abnormal frequency or prolonged duration suggesting an immune compromised status, as judged by the Investigator.
• History of serious infections with the potential for recurrence (as judged by the Investigator), with less than 4 weeks interval between resolution of serious infection and first dose of study drug, or currently active moderate to severe infection at Screening (Grade 2 or higher).
• Current or chronic history of liver disease unrelated to IgG4-RD.
• Refractory nausea and vomiting, malabsorption, external biliary shunt, bariatric surgery, or significant bowel resection that would preclude adequate rilzabrutinib/placebo absorption.
• History of solid organ transplant.
• Planned major surgical procedure during the participation in this study.
• History of drug abuse within the previous 12 months.
• Alcoholism or excessive alcohol use, defined as regular consumption of more than approximately 3 standard drinks per day.
• Prior participation in any rilzabrutinib studies or other BTK inhibitor studies.
• History of treatment with an investigational drug within 6 months or 5 half-lives of the investigational drug, whichever is longer.
• Laboratory abnormalities at the screening visit identified by the central laboratory The above information is not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.

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 · 17 центров

• Kaiser Permanente - Fontana Medical Center- Site Number : 8400015 — Fontana
• San Jose Clinical Trials- Site Number : 8400016 — San Jose
• Solace Clinical Research - Tustin- Site Number : 8400020 — Tustin
• Life Clinical Trials - Margate - Colonial Drive- Site Number : 8400002 — Margate
• Schiff Center for Liver Diseases- Site Number : 8400010 — Miami
• Vitalia Medical Research - Margate- Site Number : 8400025 — Palm Beach Gardens
• Emory University School of Medicine - Atlanta- Site Number : 8400013 — Atlanta
• Primeway Clinical Research- Site Number : 8400019 — Fayetteville
• … и ещё 9 центров

Япония · 11 центров

• Investigational Site Number : 3920004 — Kitakyushu
• Hiroshima University Hospital-Site Number : 3920007 — Hiroshima
• Investigational Site Number : 3920011 — Sapporo
• Kobe University Hospital-Site Number : 3920010 — Kobe
• Kanazawa Medical University Hospital-Site Number : 3920002 — Kahoku, Uchinada
• Investigational Site Number : 3920001 — Kanazawa
• Investigational Site Number : 3920005 — Nagaoka
• Investigational Site Number : 3920003 — Hirakata
• … и ещё 3 центра

Китай · 10 центров

• Investigational Site Number : 1560008 — Пекин
• Investigational Site Number : 1560004 — Пекин
• Investigational Site Number : 1560001 — Пекин
• Investigational Site Number : 1560012 — Чэнду
• Investigational Site Number : 1560010 — Ханчжоу
• Investigational Site Number : 1560003 — Jiazhuang
• Investigational Site Number : 1560013 — Taiyuan
• Investigational Site Number : 1560005 — Taiyuan
• … и ещё 2 центра

Чили · 5 центров

• Investigational Site Number : 1520005 — Concepción
• Centro de estudios G y C-Site Number : 1520003 — Santiago
• Investigational Site Number : 1520006 — Santiago
• Investigational Site Number : 1520001 — Santiago
• Investigational Site Number : 1520002 — Santiago

Аргентина · 4 центра

• Investigational Site Number : 0320005 — Berazategui
• Investigational Site Number : 0320003 — San Isidro
• Investigational Site Number : 0320002 — Resistencia
• Investigational Site Number : 0320004 — Buenos Aires

Германия · 4 центра

• Investigational Site Number : 2760001 — Berlin
• Investigational Site Number : 2760003 — Erlangen
• Investigational Site Number : 2760004 — Minden
• Investigational Site Number : 2760006 — Ulm

Франция · 3 центра

• AP-HP - Hôpital Beaujon-Site Number : 2500002 — Clichy
• Investigational Site Number : 2500001 — Marseille
• CHU Bordeaux - Hôpital Haut Leveque-Site Number : 2500003 — Pessac

Италия · 3 центра

• AOU Meyer IRCCS-Site Number : 3800003 — Florence
• IRCCS Ospedale San Raffaele-Site Number : 3800001 — Milan
• Centro Ricerche Cliniche di Verona s.r.l. c/o Policlinico G.B.Rossi-Site Number : 3800002 — Verona

Польша · 3 центра

• Malopolskie Badania Kliniczne sp. z. o.o.-Site Number : 6160001 — Krakow
• Investigational Site Number : 6160002 — Wroclaw
• Uniwersyteckie Centrum Kliniczne, Centrum Wsparcia Badan Klinicznych UCK Osrodek Badan Wcz — Gdansk

Испания · 3 центра

• Investigational Site Number : 7240001 — Barcelona
• Investigational Site Number : 7240002 — Barcelona
• Investigational Site Number : 7240004 — Madrid

Тайвань · 3 центра

• Investigational Site Number : 1580004 — Kaohsiung City
• Investigational Site Number : 1580001 — Taipei
• Investigational Site Number : 1580002 — Taoyuan City

Израиль · 2 центра

• Rabin MC, Outpatient Clinics Building-Site Number : 3760001 — Petah Tikva
• Sourasky Rheumatology Dept, Rishonim Building-Site Number : 3760005 — Tel Aviv

Нидерланды · 2 центра

• Erasmus Medisch Centrum-Site Number : 5280001 — Rotterdam
• UMCG-Site Number : 5280002 — Groningen

Саудовская Аравия · 2 центра

• Investigational Site Number : 6820002 — Riyadh
• Investigational Site Number : 6820001 — Riyadh

South Korea · 2 центра

• Investigational Site Number : 4100002 — Suwon
• Investigational Site Number : 4100001 — Seoul

Швеция · 2 центра

• Investigational Site Number : 7520001 — Huddinge
• Investigational Site Number : 7520002 — Uppsala

Бельгия · 1 центр

• Investigational Site Number : 0560001 — Leuven

Канада · 1 центр

• Investigational Site Number : 1240001 — Sherbrooke

Великобритания · 1 центр

• Investigational Site Number : 8260004 — Norwich

Идентификаторы

NCT: NCT07190196 · EFC17359 · U1111-1316-0266 · 2025-521398-15

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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