Oral HS-10542 for paroxysmal nocturnal hemoglobinuria

A Phase IB/II,Open Label Study to Assess Efficacy, and Safety, of HS-10542 in Adult Patients With Paroxysmal Nocturnal Hemoglobinuria (PNH) With Signs of Active Hemolysis

This study will test whether the oral drug HS-10542 can reduce hemolysis and raise hemoglobin in adults with PNH, including those not fully helped by C5 inhibitor therapy.

Quick facts

• Phase: Phase1; Phase2
• Study type: Interventional
• Enrollment: 50 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: Jiangsu Hansoh Pharmaceutical Co., Ltd. (Industry-sponsored)
• Drugs / interventions: ikuzumab, covalimab, ecucizumab, covalizumab, Prednisone
• Locations: 1 site (Hangzhou, Zhejiang)
• Trial ID: NCT07470762 on ClinicalTrials.gov

What this trial studies

This is a Phase 1b/2 open-label, multicenter trial of HS-10542, an oral small-molecule inhibitor of factor B in the alternative complement pathway, in adults with PNH and active hemolysis. Phase 1b randomizes participants 1:1 to low or high dose (stratified by current C5 inhibitor use) to determine the recommended Phase 2 dose based on safety, efficacy, and PK/PD data. Phase 2 treats participants who have an inadequate response to C5 inhibitors with the selected dose to measure effects on hemoglobin, transfusion needs, LDH, and overall safety. Vaccination against Neisseria meningitidis and Streptococcus pneumoniae (or prophylactic antibiotics when vaccination timing is insufficient) is required before starting treatment.

Who should consider this trial

Good fit: Adults aged 18–75 with confirmed PNH (clone size ≥10%), evidence of active hemolysis (LDH >1.5×ULN), and anemia or recent transfusions—including those on but inadequately helped by C5 inhibitors—are the intended participants.

Not a fit: Patients without active hemolysis, with very small PNH clones, those fully controlled on current C5 inhibitor therapy, or those unable to receive required vaccinations are unlikely to benefit from this treatment.

Why it matters

Potential benefit: If successful, HS-10542 could prevent intra- and extravascular hemolysis, raise hemoglobin, and reduce transfusion needs for people with PNH.

How similar studies have performed: Similar oral factor B inhibitors (for example, iptacopan) have shown promising results in PNH, so this mechanism has supporting evidence from other trials.

Eligibility criteria

Inclusion Criteria:

1. Men or women aged more than or equal to (≥) 18 years, and less than (≤) 75 years.
2. It was confirmed to be PNH during screening, and the clone size of red blood cells or/and granulocytes or/and monocytes was detected by flow cytopy ≥10%
3. Stable use of C5 complement inhibitor ikuzumab/covalimab for the first 6 months of random treatment
4. Have at least one blood transfusion record within the last 4 months, or sustain a hemoglobin level below 100g/L the last 4 months prior to screening.
5. The average hemoglobin level from two tests conducted by the laboratory at the time of screening is less than 100 g/L, or hemoglobin level \<100g/L before transfusion.
6. LDH \> 1.5 x Upper Limit of Normal (ULN) at the time of screening
7. Inoccution of Neisseris meningitis and Streptococcus pneumoniae vaccine at least 2 weeks before the first administration of HS-10542;
8. if HS-10542 treatment must begin less than 2 weeks after vaccination, preventive antibiotic treatment must begin at least 2 weeks after vaccination.
9. Male and female subjects with fertility must agree to adopt efficient contraceptive measures with their partners within 60/120 days from the signing of the informed consent form to the last administration,
10. Male subjects who are infertile (such as those who have undergone effective sterilization surgery) must take additional efficient contraceptive measures when it is uncertain whether they have sperm，

Exclusion Criteria:

1. Known or suspected hereditary or acquired complement deficiency
2. Currently active primary or secondary immunodeficiency
3. History of infection with pod bacteria (such as Neisseris meningitis, Streptococcus pneumoniae, etc.)
4. Patients with laboratory evidence of bone marrow failure (reticulocytes \<100x109/L; platelets \<30x109/L; neutrophils \<0.5x109/L);
5. Presence of a bone marrow failure disorder (e.g., aplastic anemia, myelodysplastic syndrome, myelofibrosis)
6. Presence of active anemia unrelated to PNH, such as renal anemia or anemia due to blood loss.
7. There is or is suspected of systemic active bacteria, virus or fungal infection 2 weeks before the first administration of HS-10542 (according to the researcher's judgment)
8. During screening, there are advanced heart disease (such as NYHA level IV),
9. unstable thrombosis events that may exist for other causes,
10. Abnormal ECG: The absolute value of QTcF (QT interval corrected by Fridericia 's formula \> 450 msec for males and \> 470 msec for females; or other clinically significant abnormalities as judged by the investigator.
11. Major surgery within 3 months prior to the first dose. \*Note: See Appendix for definitions of Grade 3/4 surgeries.
12. Known active infection requiring systemic therapy
13. Diagnosed malignant tumors in the past 5 years
14. Those who have a history of splenectomy or History of bone marrow/hematopoietic stem cells or solid organ transplantation
15. Severe or poorly controlled hypertension
16. poorly controlled diabetes
17. Those who are suspected of being allergic to experimental drugs or any ingredient in experimental drugs
18. Use any of the following drugs, unless there is a stable treatment plan before screening: a) erythropoietin (ESA), hypoxic-inducing factor proaminoyl hydroxylase inhibitor (HIF-PHI) or immunosuppressant for at least 8 weeks b) Systemic use of glucocorticoids (≤15 mg/day Prednisone or equivalent doses of glucocorticoids) at least 4 weeks c) Vitamin K antagonists (such as warfarin) have a stable international standardized ratio (INR) at least 4 weeks d) Low molecular weight heparin, oral anticoagulants such as aspirin, rvaroxaban, apifloxaban, etc. at least 4 weeks e) Iron supplements , vitamin B12, folic acid or androgen for at least 4 weeks
19. Except for C5 complement inhibitors (including but not limited to ecucizumab and covalizumab), the situation of participating in other clinical trials or using other study drugs or approved therapies for experimental use before screening, and the trial drug is still within 5 half-lives or 2 weeks
20. Participants who have previously received B-factor inhibitor treatment, with a treatment duration of no more than one week and having stopped taking the drug for more than five half-lives before screening, may not be excluded
21. During screening, there are serious concurrent diseases, such as severe kidney disease (such as eGFR\<30 mL/min/1.73 m2, dialysis),
22. ALT/ALP\>3×ULN,
23. Screening positive blood pregnancy test and breastfeeding women at the time of the visit,

Where this trial is running

Hangzhou, Zhejiang

• The First Affiliated Hospital，Zhejiang University School of Medicine — Hangzhou, Zhejiang, China (Recruiting)

Study contacts

• Study coordinator: Yan Hong Tong

Conditions Paroxysmal Nocturnal Hemoglobinuria; HS-10542; paroxysmal nocturnal hemoglobinuria（PNH）; CFB