Paroxysmal Nocturnal Hemoglobinuria, PNH
Conditions
Brief summary
This study aimed to evaluate the efficacy and safety of Lanoracopan Hydrochloride in the treatment of Paroxysmal Nocturnal Hemoglobinuria (PNH)
Detailed description
In Chinese multicenter phase 3 trials, lanoracopan 400 mg BID was evaluated over 24 weeks. In the active-controlled study (N=66, complement-naïve), the proportion achieving Hb ≥120 g/L was 50.0% (lanoracopan) versus 9.09% (eculizumab). In the single-arm study (N=20, C5 inhibitor-inadequate responders), 70% reached Hb ≥120 g/L, and 100% had Hb increase ≥20 g/L from baseline. No treatment-discontinuation due to AEs, no severe breakthrough hemolysis, no major vascular events, no encapsulated bacterial infections, and no deaths were reported across both studies. These data demonstrate superior hemoglobin correction and favorable short-term safety. However, long-term real-world effectiveness and safety profiles stratified by prior treatment (C5 inhibitors vs. other factor B inhibitors) remain uncharacterized. This observational study will enroll a diverse cohort to capture durability of Hb response, transfusion independence rate, incidence of breakthrough hemolysis and thrombosis, and adverse event patterns over extended follow-up, providing evidence to guide therapy switching and sequencing in clinical practice.
Interventions
DRUGLanoracopan Hydrochloride
400mg bid
Sponsors
Peking Union Medical College Hospital
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. Age 18-75 years. 2. Diagnosis of paroxysmal nocturnal hemoglobinuria (PNH) meeting any of the following conditions: * Newly diagnosed PNH with active hemolysis (hemoglobin \[Hb\] \<100 g/L, lactate dehydrogenase \[LDH\] \>1.5×upper limit of normal \[ULN\]); * Receiving a stable regimen of complement C5 monoclonal antibody (eculizumab) at standard dose and interval for ≥3 months, with Hb still \<120 g/L despite treatment; * Intolerant to eculizumab therapy; * Receiving standard iptacopan therapy for ≥3 months, with Hb still \<120 g/L; * Intolerant to iptacopan therapy. * Currently receiving standard lanoracopan therapy (patients who have completed lanoracopan clinical trials). 3. Vaccination against meningococcal infection (quadrivalent conjugate vaccine, MenACWY) is required prior to the first dose of study drug (Day 1). If not vaccinated within 3 years prior to Day 1, vaccination must be administered at least 14 days before Day 1; if administered within 14 days before Day 1, antibiotic prophylaxis against meningococcal infection is required until 14 days post-vaccination. 4. Vaccination against pneumococcal infection is required prior to Day 1. If not vaccinated within 5 years prior to Day 1, vaccination must be administered at least 14 days before Day 1; if administered within 14 days before Day 1, antibiotic prophylaxis against pneumococcal infection is required until 14 days post-vaccination. 5. Willing and able to provide written informed consent and comply with study procedures.
Exclusion criteria
1. Previous bone marrow or hematopoietic stem cell transplantation. 2. Previous splenectomy. 3. Known or suspected hereditary complement deficiency. 4. History of recurrent invasive infections caused by encapsulated organisms, e.g. meningococcus or pneumococcus. 5. A history of malignancy within 5 years before screening, except cured local basal cell carcinoma of the skin and carcinoma in situ of the cervix. 6. Severe concurrent illness, including severe renal disease (e.g., dialysis), advanced cardiac disease (NYHA class IV), severe pulmonary hypertension (WHO class IV), or unstable thrombotic events, judged unsuitable for participation by the investigator. 7. Any other condition that, in the investigator's opinion, may interfere with study conduct, increase subject risk, or preclude safe participation and completion, including concomitant disease, treatment, procedure, surgery, or clinically significant laboratory abnormality. 8. Pregnant or breastfeeding women.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| rate of adverse events (AEs) | During treatment, an average of 24 weeks | According to CTCAE V5.0 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of subjects maintaining Hb ≥120 g/L | 12 weeks, 24 weeks | During the treatment observation period, assess the proportion of subjects maintaining Hb ≥120 g/L every 12 weeks without red blood cell transfusion |
| changes in hemoglobin (Hb) levels | 12 weeks, 24 weeks | During the treatment observation period, evaluate changes in Hb levels every 12 weeks without red blood cell transfusion. |
| incidence of clinically significant hemolysis | 12 weeks, 24 weeks | During the treatment observation period, assess the incidence of clinically significant hemolysis every 12 weeks. |
| proportion of subjects experiencing a major adverse vascular event (MAVE) | 12 weeks, 24 weeks | During the treatment observation period, assess the proportion of subjects experiencing a MAVE every 12 weeks. |
Contacts
CONTACTBing Han
Outcome results
None listed