A Study to Evaluate the Safety and Efficacy of ZS801 in Adult Hemophilia B Patients
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|ClinicalTrials.gov Identifier: NCT05641610|
Recruitment Status : Not yet recruiting
First Posted : December 7, 2022
Last Update Posted : December 7, 2022
|Condition or disease||Intervention/treatment||Phase|
|Hemophilia B||Genetic: ZS801||Phase 1 Phase 2|
This study will seek to determine the safety, tolerability, kinetics and efficacy of a single IV infusion of ZS801.
Hemophilia B is a genetic bleeding disorder resulting in the lack of ability to produce blood-clotting factor IX (FIX). Individuals with hemophilia B suffer repeated bleeding events, which can cause chronic joint disease and sometimes leads to death due to the inability for blood to clot efficiently. The current treatment is intravenous infusion of FIX protein products, either prophylactically or in response to bleeding.
ZS801 is an adeno-associated viral (AAV) vector designed to drive expression of the human factor IX (hFIX) transgene and raise circulating levels of endogenous FIX.
Dose-escalation phase: 16 patients will be enrolled sequentially every 3 weeks or more between cohorts and administered with single infusion of ZS801. Dose escalation may occur based on the safety and FIX activity on steady state. The dose levels are as follows: 2.0×10^12vg/kg, 5.0×10^12vg/kg, 1.0×10^13vg/kg.
Dose-expansion phase: 5 patients will be enrolled and be administrated of ZS801.
Subjects will provide informed consent and then undergo screening assessments up to 6-8 weeks prior administration of ZS801. All subjects will undergo 52 weeks safety and efficacy observation.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||21 participants|
|Intervention Model:||Single Group Assignment|
|Intervention Model Description:||Hemophilia B patients|
|Masking:||None (Open Label)|
|Official Title:||A Non-randomized, Open-label, Dose-escalation, Phase I/II Study to Evaluate the Safety, Tolerability, Kinetics and Efficacy of a Single Intravenous Infusion of ZS801 in Hemophilia B Subjects With Endogenous FIX ≤2%.|
|Estimated Study Start Date :||December 2022|
|Estimated Primary Completion Date :||December 2024|
|Estimated Study Completion Date :||December 2028|
Single intravenous (i.v.) infusion of ZS801 Intervention: Gene Therapy / Gene Transfer
A novel, bioengineered adeno-associated viral (AAV) vector carrying human factor IX variant. The dose levels are as follows: 2.0×10^12vg/kg, 5.0×10^12vg/kg, 1.0×10^13vg/kg.
- Incidence of adverse events [ Time Frame: Baseline up to Week 52 ]An adverse event (AE) is any medical occurrence, the event will not relate to the treatment.
- Number of participants with clinically significant change from baseline in vital signs [ Time Frame: Baseline up to Week 52 ]Vital signs will be obtained with participants in the seated position, after having sat calmly for at least 5 minutes. The clinical significance of vital signs will be determined at the investigator's discretion.
- Number of participants with clinically significant change from baseline in physical examination findings [ Time Frame: Time Frame: Baseline up to Week 52 ]Findings will be considered to be clinically significant based on the investigator's decision.
- Number of participants with clinical laboratory abnormalities [ Time Frame: Baseline up to Week 52 ]Findings were considered to be clinically significant based on the investigator's decision.
- Antibody against AAV capsid protein [ Time Frame: Baseline up to Week 52 ]Immune response against AAV capsid will be evaluated by measurement of the binding antibody and neutralizing antibody against AAV capsid protein in plasma samples.
- Vector-derived FIX activity levels [ Time Frame: Baseline up to Week 52 ]The vector-derived endogenous FIX activity levels will be measured by One-Stage clot (OS) assay, and characterized by post-treatment population mean and its change from baseline during each visit.
- Vector-derived FIX antigen levels [ Time Frame: Baseline up to Week 52 ]The vector-derived endogenous FIX antigen levels will be characterized by post-treatment population mean, and its change from baseline during each visit.
- Vector shedding of ZS801 [ Time Frame: Baseline up to Week 52 ]Blood, saliva, urine and semen will be collected to assess clearance of vector genomes.
- Annualized bleeding rate changes from baseline [ Time Frame: Baseline up to Week 52 ]The number of bleeding episodes per participant will be recorded, and the annualized number of bleeding episodes was calculated.
- Annualized FIX consumption changes from baseline [ Time Frame: Baseline up to Week 52 ]The use of FIX replacement therapy will be recorded by dose (IU/kg) administered, and the annualized use of FIX replacement therapy will be calculated.
- Number of target joints [ Time Frame: Baseline up to Week 52 ]The target joint is a minimum of three bleeds into a single joint within a consecutive 3-month period.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05641610
|Contact: Zhang Lei, MD||+86 firstname.lastname@example.org|
|Institute of Hematology & Blood Diseases Hospital|
|Tianjin, Tianjin, China, 300020|
|Principal Investigator:||Lei Zhang, MD||Institute of Hematology & Blood Diseases Hospital|