Clinical trial NCT06978699: A Phase II Study Evaluating the Efficacy and Safety of XH-S003 Capsules in Patients With Paroxysmal Nocturnal Hemoglobinuria (PNH)
Official title: A Multicenter, Randomized, Single-blind Phase II Study Evaluating the Efficacy and Safety of XH-S003 Capsules in Patients With Paroxysmal Nocturnal Hemoglobinuria (PNH)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: PNH - Paroxysmal Nocturnal Hemoglobinuria
Keywords: Paroxysmal Nocturnal Hemoglobinuria
Lead sponsor: S-INFINITY Pharmaceuticals Co., Ltd
Sponsor class: INDUSTRY
First posted: 2025-05-18
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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


Eligibility criteria: Inclusion Criteria:

* 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;

Exclusion Criteria:

* 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;

Primary outcomes:
measure: Changes of hemoglobin compared with baseline
timeFrame: 8 weeks
Secondary outcomes:
measure: Proportion of subjects with an increase in Hb ≥20g/L compared with baseline (without RBC transfusion);
timeFrame: 8 weeks
measure: Changes in Indirect Bilirubin compared to baseline;
timeFrame: 8 weeks
measure: Changes in reticulocyte counts compared to baseline;
timeFrame: 8 weeks
measure: Proportion of subjects without RBC transfusion
timeFrame: 8 weeks
measure: Changes in LDH compared with baseline
timeFrame: 8 weeks
Other outcomes:
Locations:
city: Tianjin
country: China
facility: TianJin Medical University General Hospital
Study officials:
References: