Paroxysmal Nocturnal Hemoglobinuria (PNH)
Conditions
Brief summary
The complement system is an important component of the innate immune system. Abnormal activation, inadequate regulation and control of the complement system, as well as impaired and dysfunctional effector functions, underlie complement mediated diseases including PNH. VSA012 targeting complement system has the potential to treat a variety of diseases associated with abnormal activation of the complement system.The purpose of VSA012-1002 is to evaluate the safety, tolerability, pharmacokinetic, pharmacodynamics and efficacy of VSA012 Injection in subjects with PNH.
Interventions
DRUGVSA012
VSA012 injection
Sponsors
Bisirna Therapeutics Pte. Ltd.
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
Inclusion and
Exclusion criteria
for Groups 1-4 * Participants voluntarily participate in this clinical study, and voluntarily sign the ICF; * BMI ≥ 18.0 kg/m2; male or female; 18 to 75 years of age; * Confirmed diagnosis of PNH by clinical manifestation and flow cytometry; granulocyte clone size ≥ 10%; * Presence of one or more of PNH-related signs or symptoms within 3 months prior to screening; * Hb \< 100 g/L; * LDH value \> 1.5 × ULN; * One of the following criteria for prior drug therapy for PNH must be met: 1. Having never received any complement inhibitor therapy; 2. Having received C5, C3, or CFB complement inhibitors and having discontinued the complement inhibitor for more than 5 half-lives or 3 months prior to screening; * Participants are willing to receive meningococcal vaccine and pneumococcal vaccine at least 14 days prior to dosing. Inclusion and
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants with Treatment-Emergent Adverse Events (AEs) and/or Serious Adverse Events (SAEs) | up to Day 540 | — |
| preliminary efficacy | up to Day 540 | Percentage change from baseline in lactate dehydrogenase (LDH) by visit Change from baseline in hemoglobin (Hb) level by visit |
Secondary
| Measure | Time frame |
|---|---|
| Pharmacokinetics (PK) of VSA012 (First dose): Maximum Observed Plasma Concentration (Cmax) | Up to 48 hours post-dose |
| PK of VSA012(First dose): Time to Maximum Observed Plasma Concentration (Tmax) | Up to 48 hours post-dose |
| PK of VSA012(First dose)：Area under the concentration-time curve during the dosing interval (AUC 0-tau) | Up to 48 hours post-dose |
| PK of VSA012 (Multiple dose)：Trough concentration (C min) | Up to 48 hours post-dose |
| PK of VSA012 (Multiple dose)：Accumulation ratio of C max | Up to 48 hours post-dose |
| PK of VSA012 (Multiple dose)：AUC 0-tau | Up to 48 hours post-dose |
| PK of VSA012 (Multiple dose)：T max | Up to 48 hours post-dose |
| PK of VSA012 (Multiple dose)：C max (RacC max) | Up to 48 hours post-dose |
| PK of VSA012 (Multiple dose)：Accumulation ratio of AUC 0-tau (RacAUC 0-tau) | Up to 48 hours post-dose |
| Pharmacodynamic (PD) profile of VSA012:Change from baseline in complement factor B (CFB) and complement bypass pathway (CAP) activities | up to Day 540 |
| PD of VSA012:Change from baseline in PNH clones, including number of PNH clones in erythrocytes, number of PNH clones in granulocytes, and number of PNH clones in monocytes | up to Day 540 |
Countries
China
Contacts
PRINCIPAL_INVESTIGATORBing Han
Peking Union Medical College Hospital
PRINCIPAL_INVESTIGATORHongyan Tong
Zhejiang University
Outcome results
None listed