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

Primary Purpose

Hemophilia B

Status
Not yet recruiting
Phase
Not Applicable
Locations
China
Study Type
Interventional
Intervention
ZS801
Sponsored by
Institute of Hematology & Blood Diseases Hospital, China
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Hemophilia B

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)MaleDoes not accept healthy volunteers

Inclusion Criteria: Male ≥18 years and ≤65years of age; Confirmed diagnosis of hemophilia B, and endogenous FIX ≤2%: Have had ≥100 prior exposure days (EDs) to any recombinant and/or plasma-derived FIX protein products; 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; Agree to use reliable barrier contraception and prohibition of sperm donation until 52 weeks after the administration of ZS801. 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: Hypersensitivity to any component of the study drug (including immunosuppressants) or a condition that can not use; Inability to tolerate immunosuppressants or steroid drugs; Have FIX inhibitor as assessed by laboratory; or documented history of FIX inhibitor; Who have a history or are currently suffering from any of the following serious clinical diseases: History of malignancy or current presence of any malignancy; Have active autoimmune disease; Severe heart disease, including angina pectoris, myocardial infarction, heart failure, clinically significant congenital heart disease, heart valve disease, arrhythmia and atrioventricular block, etc.; Have underlying liver disease or history of liver disease (such as portal hypertension, ascites, splenomegaly, esophageal varices, hepatic encephalopathy or hepatic fibrosis); Have HBsAg positive or HCV-Ab positive, or are currently receiving hepatitis B or hepatitis C antiviral therapy; Diabetes mellitus that is poorly controlled after drug treatment; Uncontrolled hypertension or hypotension; laboratory values: Hemoglobin<110g/L; Platelets<100×10^9/L; aspartate aminotransferase, Alanine transaminase, alkaline phosphatase>2×ULN; Total bilirubin>1.5×ULN; Creatinine>ULN; Albumin<LLN; HIV antibody positive or Treponema pallidum antibody positive. Have AAV5 capsid neutralizing antibody titers >1:640; 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; Those who have planned surgery within 52 weeks after the infusion; Those who lost more than 400 mL of blood within 3 months before screening; Those with epilepsy, history of mental illness (such as schizophrenia, depression, mania or anxiety) or obvious mental disorder, incapacitated or incapacitated by other reasons; Patients with a history of drug abuse or alcoholism; Investigators believe that subjects have poor compliance or are expected to be less likely to complete follow-up; There are clinically significant diseases or other reasons that the researcher and/or collaborators consider unsuitable to participate in this researcher.

Sites / Locations

  • Institute of Hematology & Blood Diseases Hospital

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

ZS801

Arm Description

Single intravenous (i.v.) infusion of ZS801 Intervention: Gene Therapy / Gene Transfer

Outcomes

Primary Outcome Measures

Incidence of adverse events
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
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
Findings will be considered to be clinically significant based on the investigator's decision.
Number of participants with clinical laboratory abnormalities
Findings were considered to be clinically significant based on the investigator's decision.
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.

Secondary Outcome Measures

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.
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.
Vector shedding of ZS801
Blood, saliva, urine and semen will be collected to assess clearance of vector genomes.

Full Information

First Posted
November 9, 2022
Last Updated
November 24, 2022
Sponsor
Institute of Hematology & Blood Diseases Hospital, China
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1. Study Identification

Unique Protocol Identification Number
NCT05630651
Brief Title
The Efficacy and Safety of ZS801 in Chinese Hemophilia B Patients.
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%.
Study Type
Interventional

2. Study Status

Record Verification Date
November 2022
Overall Recruitment Status
Not yet recruiting
Study Start Date
December 2022 (Anticipated)
Primary Completion Date
December 2024 (Anticipated)
Study Completion Date
December 2028 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Institute of Hematology & Blood Diseases Hospital, China

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hemophilia B

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Model Description
Hemophilia B subjects
Masking
None (Open Label)
Allocation
N/A
Enrollment
6 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
ZS801
Arm Type
Experimental
Arm Description
Single intravenous (i.v.) infusion of ZS801 Intervention: Gene Therapy / Gene Transfer
Intervention Type
Genetic
Intervention Name(s)
ZS801
Intervention Description
A novel, bioengineered adeno-associated viral (AAV) vector carrying human factor IX variant. The dose level is 5.0×10^12vg/kg.
Primary Outcome Measure Information:
Title
Incidence of adverse events
Description
An adverse event (AE) is any medical occurrence, the event will not relate to the treatment.
Time Frame
Baseline up to Week 52
Title
Number of participants with clinically significant change from baseline in vital signs
Description
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.
Time Frame
Baseline up to Week 52
Title
Number of participants with clinically significant change from baseline in physical examination findings
Description
Findings will be considered to be clinically significant based on the investigator's decision.
Time Frame
Time Frame: Baseline up to Week 52
Title
Number of participants with clinical laboratory abnormalities
Description
Findings were considered to be clinically significant based on the investigator's decision.
Time Frame
Baseline up to Week 52
Title
Antibody against AAV capsid protein
Description
Immune response against AAV capsid will be evaluated by measurement of the binding antibody and neutralizing antibody against AAV capsid protein in plasma samples.
Time Frame
Baseline up to Week 52
Secondary Outcome Measure Information:
Title
Vector-derived FIX:C activity levels
Description
The vector-derived endogenous FIX:C activity levels will be characterized by post-treatment population mean, and its change from baseline during each visit.
Time Frame
Baseline up to Week 52
Title
Vector-derived FIX antigen levels
Description
The vector-derived endogenous FIX antigen levels will be characterized by post-treatment population mean, and its change from baseline during each visit.
Time Frame
Baseline up to Week 52
Title
Vector shedding of ZS801
Description
Blood, saliva, urine and semen will be collected to assess clearance of vector genomes.
Time Frame
Baseline up to Week 52
Other Pre-specified Outcome Measures:
Title
Annualized bleeding rate changes from baseline
Description
The number of bleeding episodes per participant will be recorded, and the annualized number of bleeding episodes was calculated.
Time Frame
Baseline up to Week 52
Title
Annualized FIX consumption changes from baseline
Description
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.
Time Frame
Baseline up to Week 52
Title
Number of target joints
Description
The target joint is a minimum of three bleeds into a single joint within a consecutive 3-month period.
Time Frame
Baseline up to Week 52
Title
Long term factor IX activity up to 10 years after vector infusion
Description
Factor IX activity measured with one- stage method
Time Frame
up to 10 years after vector infusion

10. Eligibility

Sex
Male
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Male ≥18 years and ≤65years of age; Confirmed diagnosis of hemophilia B, and endogenous FIX ≤2%: Have had ≥100 prior exposure days (EDs) to any recombinant and/or plasma-derived FIX protein products; 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; Agree to use reliable barrier contraception and prohibition of sperm donation until 52 weeks after the administration of ZS801. 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: Hypersensitivity to any component of the study drug (including immunosuppressants) or a condition that can not use; Inability to tolerate immunosuppressants or steroid drugs; Have FIX inhibitor as assessed by laboratory; or documented history of FIX inhibitor; Who have a history or are currently suffering from any of the following serious clinical diseases: History of malignancy or current presence of any malignancy; Have active autoimmune disease; Severe heart disease, including angina pectoris, myocardial infarction, heart failure, clinically significant congenital heart disease, heart valve disease, arrhythmia and atrioventricular block, etc.; Have underlying liver disease or history of liver disease (such as portal hypertension, ascites, splenomegaly, esophageal varices, hepatic encephalopathy or hepatic fibrosis); Have HBsAg positive or HCV-Ab positive, or are currently receiving hepatitis B or hepatitis C antiviral therapy; Diabetes mellitus that is poorly controlled after drug treatment; Uncontrolled hypertension or hypotension; laboratory values: Hemoglobin<110g/L; Platelets<100×10^9/L; aspartate aminotransferase, Alanine transaminase, alkaline phosphatase>2×ULN; Total bilirubin>1.5×ULN; Creatinine>ULN; Albumin<LLN; HIV antibody positive or Treponema pallidum antibody positive. Have AAV5 capsid neutralizing antibody titers >1:640; 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; Those who have planned surgery within 52 weeks after the infusion; Those who lost more than 400 mL of blood within 3 months before screening; Those with epilepsy, history of mental illness (such as schizophrenia, depression, mania or anxiety) or obvious mental disorder, incapacitated or incapacitated by other reasons; Patients with a history of drug abuse or alcoholism; Investigators believe that subjects have poor compliance or are expected to be less likely to complete follow-up; There are clinically significant diseases or other reasons that the researcher and/or collaborators consider unsuitable to participate in this researcher.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Lei Zhang, MD
Phone
+86 022-23909240
Email
zhanglei1@ihcams.ac.cn
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Lei Zhang, MD
Organizational Affiliation
Institute of Hematology & Blood Diseases Hospital, China
Official's Role
Principal Investigator
Facility Information:
Facility Name
Institute of Hematology & Blood Diseases Hospital
City
Tianjin
State/Province
Tianjin
ZIP/Postal Code
300020
Country
China

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
Individual participant data will be shared with other researchers when ZS801 is fully approved.
IPD Sharing Time Frame
Individual participant data will be shared with other researchers when ZS801 is fully approved.
IPD Sharing Access Criteria
Individual participant data will be shared with other researchers when ZS801 is fully approved and through the contact with PI.

Learn more about this trial

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

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