Paroxysmal Nocturnal Hemoglobinuria (PNH)
Conditions
Interventions
Test group:CG001 injection
Sponsors
Peking Union Medical College Hospital
Eligibility
Sex/Gender
All
Age
18 Years to 80 Years
Inclusion criteria
Inclusion criteria: 1. The participant fully understands the purpose, nature, methods and possible adverse reactions of this trial, volunteers to participate as a participant, and voluntarily signs the informed consent form before any research procedure begins; 2. Able to communicate well with the investigator, and understand and comply with various requirements of this study; 3. Male and female participants aged 18 = 50 kg for males and body weight >= 45 kg for females; 4. Participants who have been definitively diagnosed with PNH by the investigator in accordance with the PNH diagnostic criteria in the Chinese Guidelines for the Diagnosis and Treatment of Paroxysmal Nocturnal Hemoglobinuria (2024 Edition), and have a PNH granulocyte clone level > 10% (detected by flow cytometry) within 6 months before screening or during the screening period; 5. Participants have not received any complement inhibitor therapy previously; 6. At least two tests (interval >= 7 days) during screening show that the serum LDH value is > 1.5 × ULN; 7. Hb concentration must meet the following conditions: the average hemoglobin level of two tests is = 7 days; if red blood cell (RBC) transfusion is received after the first test in the screening period, only the Hb test value of the first test in the screening period needs to meet the requirement of < 10 g/dL); 8. Participants have been vaccinated with Neisseria meningitidis vaccine and Streptococcus pneumoniae vaccine within < 3 years before the start of study treatment, or plan to receive these two vaccines, and the vaccination of both vaccines should be completed at least 14 days before the start of treatment; if vaccination is performed within < 14 days before the start of treatment or after the start of treatment, appropriate prophylactic antibiotic therapy must be given at the time of the first dose of study drug, and the therapy should continue for at least 2 weeks after completion of vaccination; 9. For female participants of childbearing potential, the pregnancy test during the screening period must be negative. They must agree not to attempt pregnancy or donate eggs from the signing of informed consent to at least 3 months after the end of study drug treatment, and use effective contraceptive measures; for male participants of childbearing potential, they must agree not to donate sperm from the signing of informed consent to at least 3 months after the end of study drug treatment, and ensure that their female partners use effective contraceptive measures.
Exclusion criteria
Exclusion criteria: 1. History of hypersensitivity, allergy or immediate-type hypersensitivity reaction (defined per Sampson criteria) to any component of the investigational product, including hypersensitivity to human, humanized or murine monoclonal antibodies or any excipient of the study drug. 2. Participation in another interventional clinical trial within 1 month prior to screening, or remaining within 5 half-lives of any investigational product from another clinical trial at screening. 3. Receipt of the following medications at a stable dose for insufficient duration prior to screening: (1) Erythropoietin for less than 8 weeks; (2) Immunosuppressants (including but not limited to cyclosporine, tacrolimus, mycophenolic acid/mycophenolate mofetil, cyclophosphamide, methotrexate, etc.) for less than 8 weeks; (3) Hypoxia-inducible factor prolyl hydroxylase inhibitors for less than 8 weeks; (4) Physiological-dose glucocorticoids (prednisone or equivalent dose <20 mg/day) for less than 4 weeks; (5) Vitamin K antagonists (e.g., warfarin) with unstable international normalized ratio (INR) maintained for less than 4 weeks; (6) Low-molecular-weight heparin or oral anticoagulants (e.g., rivaroxaban) for less than 4 weeks; (7) Iron supplements, vitamin B12 or folic acid for less than 4 weeks; (8) Androgens for less than 4 weeks. 4. Laboratory evidence of bone marrow failure at screening defined as any of the following: reticulocyte count <100×10?/L; platelet count <30×10?/L (no platelet transfusion within prior 7 days or no thrombopoietic agents such as recombinant human thrombopoietin and thrombopoietin receptor agonists within prior 14 days before lab testing); absolute neutrophil count <0.5×10?/L (no short-acting granulocyte colony-stimulating factor within prior 14 days or long-acting granulocyte colony-stimulating factor within prior 28 days before lab testing). 5. Serologic/viral testing positive for any of the following: Positive hepatitis B surface antigen (HBsAg) plus detectable HBV-DNA; Positive anti-hepatitis C virus (anti-HCV) antibody; Positive treponemal antibody (TPAb); Positive anti-human immunodeficiency virus (anti-HIV) antibody. 6. Active systemic bacterial, viral or fungal infection occurring within 14 days prior to the first study drug administration. 7. Unexplained fever =38°C within 7 days prior to the first study drug administration. 8. Receipt of any live attenuated vaccine within 1 month before first dosing, or planned administration of any live attenuated vaccine throughout the study period. 9. Documented history of substance abuse within 12 months before screening, as assessed by the Investigator. 10. History of any malignancy within 5 years prior to screening, except for cured basal cell carcinoma of the skin or in-situ cervical carcinoma. 11. Prior splenectomy or planned splenectomy during the study period. 12. Previous allogeneic hematopoietic stem cell transplantation. 13. Recurrent invasive infection caused by encapsulated bacteria (e.g., Neisseria meningitidis, Streptococcus pneumoniae) or Mycobacterium tuberculosis. 14. Active primary or secondary immunodeficiency, confirmed or suspected inherited complement deficiency disorder. 15. Presence of severe concomitant diseases deemed ineligible for trial participation by the Investigator, including but not limited to severe hepatic impairment, advanced renal disease (eGFR <30 mL/min/1.73 m²), unstable angina, or chronic anemia unrelated to paroxysmal nocturnal hemoglobinuria (PNH)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The proportion of participants who had an Hb increase of >=20 g/L compared with baseline in at least 3 of the 4 tests during the treatment period from week 18 to week 24, without red blood cell transfusion after 2 weeks of treatment.; | — |
Secondary
| Measure | Time frame |
|---|---|
| The primary efficacy endpoint was the proportion of participants achieving at least 3 out of 4 hemoglobin (Hb) measurements = 120 g/L during the treatment period from Week 18 to Week 24, in the absence of red blood cell transfusions after the first 2 weeks of treatment.;Change from baseline in mean hemoglobin (Hb) levels and percentage change between Weeks 18 and 24 of treatment; | — |
Countries
China
Contacts
Public ContactBing Han
Peking Union Medical College Hospital
Outcome results
None listed