Clinical trial NCT06848296: A Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Preliminary Efficacy of of VSA012 in Subjects with Paroxysmal Nocturnal Hemoglobinuria(PNH)
Official title: Phase Ib Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Preliminary Efficacy of VSA012 Injection in Subjects with Paroxysmal Nocturnal Hemoglobinuria(PNH) Who Are Complement Inhibitor Naïve or Have Not Received Complement Inhibitor Therapy Recently
Study type: OBSERVATIONAL
Overall status: NOT_YET_RECRUITING
Conditions: Paroxysmal Nocturnal Hemoglobinuria (PNH)
Lead sponsor: Visirna Therapeutics HK Limited
Sponsor class: INDUSTRY
First posted: 2025-02-27
Enrollment: 16
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: subjects with PNH

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.

Detailed description: This is a multi-center, non-randomized, open-label Phase 1b study to evaluate the safety and tolerability, pharmacokinetic and pharmacodynamic profiles of VSA012 Injection in Chinese subjects with PNH, as well as to explore preliminary efficacy.

The VSA012 60 mg dose group and VSA012 120 mg dose group were initially proposed in this study; adjustments will be made based on data obtained in a single ascending dose study in healthy adult Chinese subjects (VSA012-1001) and stepwise data from this study, taking full account of subject safety. Enrollment in the 60 mg dose group of this study was not initiated until 15 days postdose safety assessments were completed for subjects in the 60 mg dose group of Study VSA012-1001; enrollment in the 120 mg dose group of Study VSA012-1001 was not initiated until 15 days postdose safety assessments were completed for subjects in the 120 mg dose group.

About 8 subjects with PNH will be enrolled in each group in this study and will receive VSA012 Injection 60 mg or V SA012 Injection 12 0 mg on D1 and D29, respectively; based on full consideration of the safety of subjects, the dosing regimen may be adjusted in combination with the data gradually obtained from the VSA012-1001 study and this study. Participants may receive concomitant supportive care permitted in this study throughout the study and continue to be followed for 24 weeks following completion of D29 dosing.

This study includes: Screening Period, Treatment Period, Follow-up Period.

Eligibility criteria: Inclusion Criteria:

* Voluntarily participate in this clinical study, understand and follow study procedures and voluntarily sign the ICF;
* Body mass index (BMI) ≥ 18.0 kg/m2 , male or female, ≥ 18 years of age (including the critical value) at the time of signing the ICF;
* Confirmed diagnosis of PNH by clinical presentation and flow cytometry; flow cytometry within 6 months prior to or during screening consistent with granulocyte clonal size ≥ 10%;
* Hb \< 100 g/L；
* Lactate dehydrogenase (LDH) \> 1.5 × ULN；
* Subject is willing to receive 4-valent meningococcal vaccine, Streptococcus pneumoniae vaccine at least 14 days prior to dosing. If 4-valent meningococcal vaccine is administered within 3 years before the first dose, it may not be repeated; if S. pneumoniae vaccine is administered within 5 years, it may not be repeated;
* Agreed to use a highly effective method of contraception throughout the study and for 12 months after the last study dose.

Exclusion Criteria:

* History of hypersensitivity to VSA012 or its excipients;
* Use of any complement inhibitor within 3 months before screening or within 5 half-lives (whichever is longer);
* Infections prior to first dose;
* Prior splenectomy;
* Previously suspected/confirmed hereditary complement deficiency;
* History of recurrent invasive infection with encapsulated bacteria such as meningococcus or pneumococcus;
* Severe aplastic anemia (SAA) at screening and receiving immunosuppressive therapy;
* Patients with previous autoimmune diseases requiring systemic treatment, such as human immunodeficiency virus (HIV) infection, except for corticosteroid replacement therapy for thyroid, adrenal or pituitary insufficiency;
* History of allogeneic transplantation, stem cell transplantation, organ transplantation or other transplant.

Primary outcomes:
measure: Number of Participants with Treatment-Emergent Adverse Events (AEs) and/or Serious Adverse Events (SAEs)
timeFrame: up to Day 196
measure: preliminary efficacy
timeFrame: up to Day 196
Secondary outcomes:
measure: Pharmacokinetics (PK) of VSA012 (First dose): Maximum Observed Plasma Concentration (Cmax)
timeFrame: Up to 48 hours post-dose
measure: PK of VSA012(First dose): Time to Maximum Observed Plasma Concentration (Tmax)
timeFrame: Up to 48 hours post-dose
measure: PK of VSA012(First dose)：Area under the concentration-time curve during the dosing interval (AUC 0-tau)
timeFrame: Up to 48 hours post-dose
measure: PK of VSA012 (Multiple dose)：Trough concentration (C min)
timeFrame: Up to 48 hours post-dose
measure: PK of VSA012 (Multiple dose)：Accumulation ratio of C max
timeFrame: Up to 48 hours post-dose
measure: PK of VSA012 (Multiple dose)：AUC 0-tau
timeFrame: Up to 48 hours post-dose
measure: PK of VSA012 (Multiple dose)：T max
timeFrame: Up to 48 hours post-dose
measure: PK of VSA012 (Multiple dose)：C max (RacC max)
timeFrame: Up to 48 hours post-dose
measure: PK of VSA012 (Multiple dose)：Accumulation ratio of AUC 0-tau (RacAUC 0-tau)
timeFrame: Up to 48 hours post-dose
measure: Pharmacodynamic (PD) profile of VSA012:Change from baseline in complement factor B (CFB) and complement bypass pathway (CAP) activities
timeFrame: up to Day 196
measure: 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
timeFrame: up to Day 196
Other outcomes:
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