This was a phase 1b/2,open label, multi-center study to assess efficacy and safety of HS-10542 in adulte patients with paroxysmal nocturnal hemoglobinuria (PNH) with signs of active hemolysis.
HS-10542 is a novel oral small molecular weight compound that inhibits factor B (FB) of the alternative pathway (AP). Blockade of the AP with oral HS-10542 has the potential to prevent both intra - and extravascular hemolysis. This study consists of a dose exporation(Ph1b) and a dose expansion(Ph 2): Phase Ib:In participants with paroxysmal nocturnal hemoglobinuria (PNH), two dose levels of HS-10542 will be explored (low dose; high dose randomized 1:1), stratified by whether the patient is currently receiving C5 complement inhibitor therapy. Based on an integrated assessment of interim data on the safety, efficacy, and PK/PD profile of HS-10542 in the target population, the recommended Phase II dose (RP2D) will be determined. Phase II:Based on the safe and effective dose identified in Phase Ib, the efficacy and safety of HS-10542 will be evaluated in participants with PNH who have an inadequate response to C5 complement inhibitor therapy.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
50
The First Affiliated Hospital,Zhejiang University School of Medicine
Hangzhou, Zhejiang, China
RECRUITINGPhase 1b: Incidence and severity of adverse events
Time frame: 12 weeks
Phase 2: In the absence of red blood cell infusion the proportion of subjects with at least 3 times of ≥120 g/L of hemoglobin level measured 4 times between weeks 18 and 24
Time frame: From the 18th to the 24th week
Phase 1b: In the absence of red blood cell infusion the proportion of subjects of ≥120 g/L of hemoglobin level between weeks 3 and 12
Time frame: From the 3th to the 12th week
Phase 1b: the Proportion of Participants With Sustained Increase in Hemoglobin Levels From Baseline of ≥ 20g/L in the Absence of Red Blood Cell Transfusions
Time frame: hemoglobin between Day 15 and Day 84 and absence of transfusions
Phase 1b: The proportion of subjects who did not receive red blood cell infusion from week 3 to week 12
Time frame: From the 3th to the 12th week
Phase 1b: Change in LDH level from baseline
Time frame: 12 weeks
Ph1b:change from baseline in hemoglobin concentration
Time frame: 12 weeks
Phase 1b: Change From Baseline in Hgb.LDH.free-Hgb. haptoglobin and ferritin
Time frame: by week 2 and week 4
Phase 1b: The number of red blood cell units transfused by the participants who received blood transfusions
Time frame: 12 weeks
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Phase 1b: The average change of the score of Chronic Disease Treatment Function Assessment (FACIT) compared to the baseline
The FACIT-F is a 13 -item, self-reported PRO measure assessing an individual's level of fatigue during their usual daily activities over the past week. This questionnaire is part of the FACIT measurement system, a compilation of questions measuring health-related QoL in patients with cancer and other chronic illnesses. The FACIT-fatigue assesses the level of fatigue using a 4-point Likert scale ranging from 0 (not at all) to 4 (very much). Scores range from 0 to 52, with higher scores indicating greater fatigue.
Time frame: Baseline and week 2, week 4, week 8, week 12
Phase 1b: The incidence of breakthrough hemolysis(BTH)from Week 1 to week 12
Time frame: From the 1th to the 12th week
Phase 1b: The incidence of Major Adverse Vascular Events(MAVEs) from Week 1 to week 12
MAVEs are recorded on the AE page/. MAVEs include but are not limited to the following conditions:Acute peripheral vascular occlusion; Gangrene, amputation (non-traumatic, non-diabetic participants); Transient ischemic attack; Cerebral artery/vein occlusion/cerebrovascular accident; Hepatic/portal vein thrombosis (Budd-Chiari syndrome); Mesenteric/visceral artery or vein thrombosis; Unstable angina; Myocardial infarction; Pulmonary embolism; Renal artery/vein thrombosis; Thrombophlebitis/deep vein thrombosis.
Time frame: From the 1th to the 12th week
Phase 2: the Proportion of Participants With Sustained Increase in Hemoglobin Levels From Baseline of ≥ 20 g/L in the Absence of Red Blood Cell Transfusions
Time frame: From the 18th to the 24th week
Phase 2: The proportion of subjects who did not receive red blood cell infusion from week 3 to week 24
Time frame: From the 3th to the 24th week
Phase 2: the average change of Hemoglobin compared to the baseline
Time frame: From the 18th to the 24th week
Phase 2: the average change of Ret compared to the baseline
Time frame: From the 18th to the 24th week
Phase 2: the average change of LDH compared to the baseline
Time frame: From the 18th to the 24th week
Phase 2: Chronic Disease Treatment Function Assessment (FACIT) from weeks 18 to 24- the average change of the score compared to the baseline
The FACIT-F is a 13 -item, self-reported PRO measure assessing an individual's level of fatigue during their usual daily activities over the past week. This questionnaire is part of the FACIT measurement system, a compilation of questions measuring health-related QoL in patients with cancer and other chronic illnesses. The FACIT-fatigue assesses the level of fatigue using a 4-point Likert scale ranging from 0 (not at all) to 4 (very much). Scores range from 0 to 52, with higher scores indicating greater fatigue.
Time frame: From the 18h to the 24th week
Phase 2: Incidence and severity of adverse events
Time frame: From the 1th to the 24th week