A Phase II Study Evaluating the Efficacy and Safety of XH-S003 Capsules in Patients With Paroxysmal Nocturnal Hemoglobinuria (PNH)

Официальное название

A Multicenter, Randomized, Single-blind Phase II Study Evaluating the Efficacy and Safety of XH-S003 Capsules in Patients With Paroxysmal Nocturnal Hemoglobinuria (PNH)

Обзор

This is a multicenter, randomized, single-blind Phase II trial to evaluate the efficacy and safety of XH-S003 capsules in PNH patients. About 24 PNH patients will be enrolled and randomized to three dose levels and take XH-S003 capsules orally

Вмешательства

• Препарат XH-S003 Capsule
  25mg \& 100mg

Первичные конечные точки

• Changes of hemoglobin compared with baseline [Срок оценки: 8 weeks]

Вторичные конечные точки (5)

• Proportion of subjects with an increase in Hb ≥20g/L compared with baseline (without RBC transfusion); [Срок оценки: 8 weeks]
• Changes in Indirect Bilirubin compared to baseline; [Срок оценки: 8 weeks]
• Changes in reticulocyte counts compared to baseline; [Срок оценки: 8 weeks]
• Proportion of subjects without RBC transfusion [Срок оценки: 8 weeks]
• Changes in LDH compared with baseline [Срок оценки: 8 weeks]

Критерии участия

Критерии включения

• Male or female with aged ≥18 years old;
• Weight ≥40 kg and BMI≥18 kg/m2 ;
• Diagnosed with PNH: with red blood cell or granulocyte clone levels >10% detected by flow cytopy within 6 months prior to screening or during screening;
• Patients who have not previously received any complement inhibitor therayp;
• LDH > 1.5×ULN detected two times during the screening period (interval of 2 to 8 weeks);
• Hb meets one of the following conditions: (1) Hb <100 g/L at the first screening visit, and subjects receive RBC transfusion because of PNH-related anemia during the screening period; (2) The average Hb of two tests during the screening period <100 g/L (interval of 2\~8 weeks);
• Vaccination against Neisseria meningitidis and Streptococcus pneumoniae before the first administration. If the subject has not been vaccinated previously or requires booster vaccination (according to local vaccination policies), vaccination must be administered at least 2 weeks before the first administration. If the first administration must begin less than 2 weeks after vaccination, preventive antibiotic treatment must begin at least 2 weeks after vaccination;

Критерии исключения

• Subjects with laboratory evidence of bone marrow failure during the screening period (reticulocyte count <100×109/L, platelet count <30×109/L, or neutrophil count <0.5×109/L);
• Subjects receiving other therapies prior to screening who have not achieved the following treatment durations:

• Erythropoietin or immunosuppressants for at least 8 weeks; • Systemic corticosteroids for at least 4 weeks; • Iron supplements, vitamin B12, or folic acid for at least 4 weeks; • Anticoagulants: Vitamin K antagonists for at least 4 weeks with stable international normalized ratio (INR) (as determined by the investigator), low molecular weight heparin for at least 4 weeks; • Hypoxic-inducing factor prolyl hydroxylase inhibitors (HIF-PHI) for at least 8 weeks; • Androgens for at least 4 weeks;
• A history of bone marrow/hematopoietic stem cell or solid organ transplantation;
• Alanine aminotransferase (ALT), γ-glutamyl transpeptidase (GGT), or alkaline phosphatase (ALP) >3×ULN at screening; - Positive HIV antibody, active syphilis infection, positive HBsAg, active HCV infection, or active tuberculosis infection at screening;
• Known or suspected immunodeficiency diseases or hereditary complement deficiency at screening;
• A history of Neisseria meningitidis infection;
• Subjects with chronic active or recurrent infections within 1 year prior to screening;
• Subjects with systemic active bacterial, viral (including COVID-19), or fungal infections within 2 weeks prior to the first administration; subjects with body temperature >38°C within 7 days prior to the first administration;

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

Простое слепое

Основная цель

Лечение

Центры проведения

Китай · 1 центр

• TianJin Medical University General Hospital — Тяньцзинь

Идентификаторы

NCT: NCT06978699 · XH-S003-II-101

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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