The Efficacy and Safety of ZS801 in Chinese Hemophilia B Patients.

Hemophilia B Clinical Trial

Official title:

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%.

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05630651
• Other study ID #: ZS801-02
• Status: Not yet recruiting
• Phase: N/A
• Start date: December 2022
• Est. completion date: December 2028

Study information

• Verified date: November 2022
• Source: Institute of Hematology & Blood Diseases Hospital
• Contact: Lei Zhang, MD
• Phone: +86 022-23909240
• Email: zhanglei1[@]ihcams.ac.cn
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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%.

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

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 6
• Est. completion date: December 2028
• Est. primary completion date: December 2024
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years to 65 Years

Eligibility

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.

Related Conditions & MeSH terms

• Hemophilia A
• Hemophilia B

Intervention

Genetic:
• ZS801
A novel, bioengineered adeno-associated viral (AAV) vector carrying human factor IX variant. The dose level is 5.0×10^12vg/kg.

Locations

Country	Name	City	State
China	Institute of Hematology & Blood Diseases Hospital	Tianjin	Tianjin

Sponsors (1)

Lead Sponsor	Collaborator
Institute of Hematology & Blood Diseases Hospital

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Annualized bleeding rate changes from baseline	The number of bleeding episodes per participant will be recorded, and the annualized number of bleeding episodes was calculated.	Baseline up to Week 52
Other	Annualized FIX consumption changes from baseline	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.	Baseline up to Week 52
Other	Number of target joints	The target joint is a minimum of three bleeds into a single joint within a consecutive 3-month period.	Baseline up to Week 52
Other	Long term factor IX activity up to 10 years after vector infusion	Factor IX activity measured with one- stage method	up to 10 years after vector infusion
Primary	Incidence of adverse events	An adverse event (AE) is any medical occurrence, the event will not relate to the treatment.	Baseline up to Week 52
Primary	Number of participants with clinically significant change from baseline in vital signs	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.	Baseline up to Week 52
Primary	Number of participants with clinically significant change from baseline in physical examination findings	Findings will be considered to be clinically significant based on the investigator's decision.	Time Frame: Baseline up to Week 52
Primary	Number of participants with clinical laboratory abnormalities	Findings were considered to be clinically significant based on the investigator's decision.	Baseline up to Week 52
Primary	Antibody against AAV capsid protein	Immune response against AAV capsid will be evaluated by measurement of the binding antibody and neutralizing antibody against AAV capsid protein in plasma samples.	Baseline up to Week 52
Secondary	Vector-derived FIX:C activity levels	The vector-derived endogenous FIX:C activity levels will be characterized by post-treatment population mean, and its change from baseline during each visit.	Baseline up to Week 52
Secondary	Vector-derived FIX antigen levels	The vector-derived endogenous FIX antigen levels will be characterized by post-treatment population mean, and its change from baseline during each visit.	Baseline up to Week 52
Secondary	Vector shedding of ZS801	Blood, saliva, urine and semen will be collected to assess clearance of vector genomes.	Baseline up to Week 52