A Study to Investigate the Efficacy, Safety, and Pharmacokinetics of Oral Rilzabrutinib Compared With Placebo in Participants 18 Years of Age and Older With Warm Autoimmune Hemolytic Anemia

Официальное название

A Phase 3, Multicenter, Randomized, Double-blind, Placebo-controlled, Parallel-group Study With an Open-label Period and Long-term Extension to Assess the Efficacy and Safety of Rilzabrutinib in Participants With Warm Autoimmune Hemolytic Anemia (wAIHA)

Обзор

This is a parallel-group, Phase 3, double-blind, 2-arm study to investigate the efficacy, safety, PK and PD of oral rilzabrutinib in achieving durable Hb response (DHR) compared with placebo in approximately 90 male and female participants ≥ 18 years of age with a confirmed diagnosis of primary wAIHA. Following a 4-week screening period, eligible participants will be randomized in a 2:1 ratio to receive rilzabrutinib or placebo in primary analysis period (PAP) for a duration of up to 24 weeks. All participants who completed PAP will then continue in open-label period (OLP) to receive rilzabrutinib for a duration of 28 weeks. Upon the completion of OLP, only participants who demonstrate Hb increase during the last 8 weeks of OLP per specified criteria in the protocol will be eligible to continue in long-term extension (LTE) of the study. The duration of the LTE period will be from the first-participant-in (FPI)-LTE until the last participant completes 52 weeks in LTE. The safety follow-up period of this study following treatment completion or discontinuation will be 2 weeks.

Вмешательства

• Препарат rilzabrutinib
  Pharmaceutical form:tablet-Route of administration:oral
• Препарат placebo
  Pharmaceutical form:tablet-Route of administration:oral

Первичные конечные точки

• Proportion of participants achieving DHR. DHR is defined as an increase of Hb by ≥2 g/dL from baseline on at least two thirds of evaluable scheduled visits between Week 12 and Week 24 (inclusive) in the PAP [Срок оценки: By Week 24]

Вторичные конечные точки (7)

• Proportion of participants achieving overall Hb response (response [R] or complete response [CR]) by Week 24 of treatment in the PAP [Срок оценки: By Week 24]
• Change from baseline in fatigue total score as measured by Functional Assessment of Chronic Illness Therapy (FACIT) - fatigue at Week 24 [Срок оценки: Baseline to Week 24]
• The time taken (days) to achieve the first Hb increase by ≥2 g/dL from baseline during the PAP in the previous 14 days and in the absence of rescue medication in the previous 6 weeks [Срок оценки: Until Week 24]
• Change from baseline in levels of LDH at Week 24 [Срок оценки: Baseline to Week 24]
• Proportion of participants requiring use of rescue therapy after Week 4 of treatment during the PAP [Срок оценки: Until Week 24]
• Change from baseline in dyspnea severity score as measured by FACIT-Dyspnea at Week 24 [Срок оценки: Baseline to Week 24]
• Incidence of treatment-emergent adverse events (TEAE), treatment-emergent serious adverse events (SAEs), treatment-emergent adverse events of special interest, as well as clinical laboratory evaluations, vital sign, physical exam, and electrocardiograms [Срок оценки: Until Week 104]

Критерии участия

Критерии включения

• Male and female participants with a documented (confirmed) diagnosis of primary wAIHA for at least 6 months.
• Participants who have previously failed to maintain a sustained response after treatment with CS (CS-resistance \[defined as failure to obtain hemoglobin response within 3 weeks on at least 1 mg/kg or 60 mg prednisone or equivalent per day\], CS-dependent wAIHA \[defined as need to continue on prednisone or equivalent at a dose of >10 mg/day to maintain a response\]), or are intolerant or ineligible to CS (defined as with contraindications, pre-existing medical conditions or CS-related complications that may render CS intolerant or ineligible per the best clinical judgement of the investigators).
• Participants with Eastern Cooperative Oncology Group (ECOG) performance status Grade 2 or lower.
• 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

• Participants with clinically significant medical history or ongoing chronic illness that would jeopardize the safety of the participant or compromise the quality of the data derived from his or her participation in the study as determined by the Investigator.
• Participants with medical history of lymphoma, leukemia, or any malignancy within the past 5 years except for basal cell or squamous epithelial carcinomas of the skin that have been resected with no evidence of metastatic disease for the past 3 years.
• Participants with symptomatic herpes zoster within 3 months prior to screening.
• Participants with mixed wAIHA, or secondary wAIHA from any cause including drugs, Evans Syndrome, lymphoproliferative disorders (low count monoclonal B-cell lymphocytosis is allowed), infectious or autoimmune disease, or active hematologic malignancies. Participants with positive antinuclear antibodies but without a definitive diagnosis of an autoimmune disease are allowed.
• Participants with history of myelodysplastic syndrome.
• Participants with uncontrolled or active HBV infection or Active HCV infection.
• HIV infection.
• Participants with history of solid organ transplant.
• Participants with a history of active or latent tuberculosis (TB).
• Splenectomy within 12 weeks before screening and planned surgery during the PAP.
• Concurrent treatment with other experimental/investigational drugs within 30 days or 5 half-lives, whichever is longer, prior to treatment start. Participants who previously received treatment with BTK inhibitors for wAIHA before Day 1 (randomization) are not eligible.
• Sensitivity to any of the study interventions, or components thereof, or drug or other allergy that, in the opinion of the Investigator, contraindicates participation in the study.

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 · 23 центра

• Mayo Clinic in Arizona - Phoenix- Site Number : 8400032 — Phoenix
• Noble Clinical Research- Site Number : 8400003 — Tucson
• City of Hope National Medical Center- Site Number : 8400023 — Duarte
• USC Norris Comprehensive Cancer Center- Site Number : 8400007 — Los Angeles
• Stanford University Medical Center- Site Number : 8400026 — Stanford
• Lundquist Institute for Biomedical Innovation at Harbor - UCLA Medical Center- Site Number — Torrance
• Yale University School of Medicine- Site Number : 8400027 — New Haven
• MedStar Georgetown University Hospital- Site Number : 8400004 — Washington D.C.
• … и ещё 15 центров

Япония · 13 центров

• Investigational Site Number : 3920007 — Nagoya
• Investigational Site Number : 3920013 — Tsuchiura
• Investigational Site Number : 3920006 — Kanazawa
• Investigational Site Number : 3920012 — Fujisawa
• Investigational Site Number : 3920003 — Suita
• Investigational Site Number : 3920001 — Iruma
• Investigational Site Number : 3920010 — Kofu
• Investigational Site Number : 3920015 — Fukuoka
• … и ещё 5 центров

Китай · 12 центров

• Investigational Site Number : 1560001 — Пекин
• Investigational Site Number : 1560007 — Chengde
• Investigational Site Number : 1560011 — Гуанчжоу
• Investigational Site Number : 1560005 — Гуанчжоу
• Investigational Site Number : 1560009 — Hohhot
• Investigational Site Number : 1560003 — Nanchang
• Investigational Site Number : 1560012 — Nanchang
• Investigational Site Number : 1560004 — Сучжоу
• … и ещё 4 центра

Италия · 10 центров

• Investigational Site Number : 3800004 — Florence
• Investigational Site Number : 3800010 — Genoa
• Investigational Site Number : 3800001 — Milan
• Investigational Site Number : 3800005 — Naples
• Investigational Site Number : 3800002 — Meldola
• Investigational Site Number : 3800009 — Novara
• Investigational Site Number : 3800006 — Palermo
• Investigational Site Number : 3800007 — Trieste
• … и ещё 2 центра

Греция · 5 центров

• Investigational Site Number : 3000002 — Athens
• Investigational Site Number : 3000005 — Larissa
• Investigational Site Number : 3000004 — Pátrai
• Investigational Site Number : 3000003 — Pátrai
• Investigational Site Number : 3000001 — Thessaloniki

Испания · 5 центров

Список центров уточняется — проверьте первичный протокол.

Израиль · 4 центра

• Investigational Site Number : 3760001 — Afula
• Investigational Site Number : 3760007 — Haifa
• Investigational Site Number : 3760005 — Kefar Sava
• Investigational Site Number : 3760002 — Tel Aviv

Аргентина · 3 центра

• Investigational Site Number : 0320001 — Rosario
• Investigational Site Number : 0320003 — Buenos Aires
• Investigational Site Number : 0320002 — Buenos Aires

Бразилия · 3 центра

• Hemoes - Centro Estadual de Hemoterapia e Hematologia Marcos Daniel Santos- Site Number : — Vitória
• Universidade Federal de Goias- Site Number : 0760001 — Goiânia
• Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo- Site Number : — São Paulo

Дания · 3 центра

• Investigational Site Number : 2080003 — Aarhus
• Investigational Site Number : 2080002 — Copenhagen
• Investigational Site Number : 2080001 — Odense

Австрия · 2 центра

• Investigational Site Number : 0400001 — Vienna
• Investigational Site Number : 0400002 — Vienna

Чехия · 2 центра

• Investigational Site Number : 2030002 — Prague
• Investigational Site Number : 2030001 — Brno

Германия · 2 центра

• Investigational Site Number : 2760003 — Berlin
• Investigational Site Number : 2760001 — Essen

Венгрия · 2 центра

• Investigational Site Number : 3480004 — Budapest
• Investigational Site Number : 3480002 — Debrecen

Нидерланды · 2 центра

Список центров уточняется — проверьте первичный протокол.

Польша · 2 центра

Список центров уточняется — проверьте первичный протокол.

Швеция · 2 центра

Список центров уточняется — проверьте первичный протокол.

Идентификаторы

NCT: NCT07086976 · EFC17360 · U1111-1314-5112 · 2024-517972-39

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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