Hemophilia B
Conditions
Brief summary
A non-randomized, open-label study to evaluate the safety, kinetics and efficacy of a single intravenous infusion of ZS801 in hemophilia B subjects with endogenous FIX ≤2%.
Detailed description
This study will seek to determine the safety, kinetics and efficacy of a single IV infusion of ZS801. The dose level is 5.0×10\^12vg/kg; Dose addition may occur based on the safety and FIX activity on steady state. Subjects will provide informed consent and then undergo screening assessments up to 6 weeks prior administration of ZS801. All subjects will undergo 52 weeks safety and efficacy observation. Then subjects
Interventions
GENETICZS801
A novel, bioengineered adeno-associated viral (AAV) vector carrying human factor IX variant. The dose level is 5.0×10\^12vg/kg.
Sponsors
Institute of Hematology & Blood Diseases Hospital, China
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Hemophilia B subjects
Eligibility
Sex/Gender
MALE
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
1. Male ≥18 years and ≤65years of age; 2. Confirmed diagnosis of hemophilia B, and endogenous FIX ≤2%: 3. Have had ≥100 prior exposure days (EDs) to any recombinant and/or plasma-derived FIX protein products; 4. The subject had at least 3 or more bleeding events and/or chronic hemophilia arthritis in one or more joints in the previous 1 year requiring treatment with FIX agents; 5. Agree to use reliable barrier contraception and prohibition of sperm donation until 52 weeks after the administration of ZS801. 6. Subjects voluntarily participate and are fully informed, fully understand the research and can comply with the requirements of the research protocol, are willing to complete the research as planned, and voluntarily cooperate with the provision of biological samples for testing.
Exclusion criteria
1. Hypersensitivity to any component of the study drug (including immunosuppressants) or a condition that can not use; 2. Inability to tolerate immunosuppressants or steroid drugs; 3. Have FIX inhibitor as assessed by laboratory; or documented history of FIX inhibitor; 4. Who have a history or are currently suffering from any of the following serious clinical diseases: 1. History of malignancy or current presence of any malignancy; 2. Have active autoimmune disease; 3. Severe heart disease, including angina pectoris, myocardial infarction, heart failure, clinically significant congenital heart disease, heart valve disease, arrhythmia and atrioventricular block, etc.; 4. Have underlying liver disease or history of liver disease (such as portal hypertension, ascites, splenomegaly, esophageal varices, hepatic encephalopathy or hepatic fibrosis); 5. Have HBsAg positive or HCV-Ab positive, or are currently receiving hepatitis B or hepatitis C antiviral therapy; 6. Diabetes mellitus that is poorly controlled after drug treatment; 7. Uncontrolled hypertension or hypotension; 5. laboratory values: 1. Hemoglobin\<110g/L; 2. Platelets\<100×10\^9/L; 3. aspartate aminotransferase, Alanine transaminase, alkaline phosphatase\>2×ULN; 4. Total bilirubin\>1.5×ULN; 5. Creatinine\>ULN; 6. Albumin\<LLN; 7. HIV antibody positive or Treponema pallidum antibody positive. 6. Have AAV5 capsid neutralizing antibody titers \>1:640; 7. Those who have received clinical trials of gene therapy before screening, or have used FIX clinical trial drugs within 1 month, or participated in other drug/device clinical trials within 3 months, or plan to participate in other clinical trials during this study; 8. Those who have planned surgery within 52 weeks after the infusion; 9. Those who lost more than 400 mL of blood within 3 months before screening; 10. Those with epilepsy, history of mental illness (such as schizophrenia, depression, mania or anxiety) or obvious mental disorder, incapacitated or incapacitated by other reasons; 11. Patients with a history of drug abuse or alcoholism; 12. Investigators believe that subjects have poor compliance or are expected to be less likely to complete follow-up; 13. There are clinically significant diseases or other reasons that the researcher and/or collaborators consider unsuitable to participate in this researcher.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of participants with clinical laboratory abnormalities | Baseline up to Week 52 | Findings were considered to be clinically significant based on the investigator's decision. |
| Number of participants with clinically significant change from baseline in vital signs | 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. |
| Incidence of adverse events | 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 physical examination findings | Time Frame: Baseline up to Week 52 | Findings will be considered to be clinically significant based on the investigator's decision. |
| Antibody against AAV capsid protein | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Vector shedding of ZS801 | Baseline up to Week 52 | Blood, saliva, urine and semen will be collected to assess clearance of vector genomes. |
| Vector-derived FIX:C activity levels | Baseline up to Week 52 | The vector-derived endogenous FIX:C activity levels will be characterized by post-treatment population mean, and its change from baseline during each visit. |
| Vector-derived FIX antigen levels | 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. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Annualized bleeding rate changes from baseline | Baseline up to Week 52 | The number of bleeding episodes per participant will be recorded, and the annualized number of bleeding episodes was calculated. |
| Long term factor IX activity up to 10 years after vector infusion | up to 10 years after vector infusion | Factor IX activity measured with one- stage method |
| Number of target joints | Baseline up to Week 52 | The target joint is a minimum of three bleeds into a single joint within a consecutive 3-month period. |
| Annualized FIX consumption changes from baseline | 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. |
Countries
China
Contacts
Primary ContactLei Zhang, MD
Outcome results
None listed