Clinical trial NCT05630651: 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
Overall status: RECRUITING
Phase: NA
Conditions: Hemophilia B
Lead sponsor: Institute of Hematology & Blood Diseases Hospital, China
Sponsor class: OTHER
First posted: 2022-11-30
Enrollment: 6
Sex: MALE
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Hemophilia B subjects
Primary purpose: TREATMENT

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

Eligibility criteria: 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.

Primary outcomes:
measure: Incidence of adverse events
timeFrame: Baseline up to Week 52
measure: Number of participants with clinically significant change from baseline in vital signs
timeFrame: Baseline up to Week 52
measure: Number of participants with clinically significant change from baseline in physical examination findings
timeFrame: Time Frame: Baseline up to Week 52
measure: Number of participants with clinical laboratory abnormalities
timeFrame: Baseline up to Week 52
measure: Antibody against AAV capsid protein
timeFrame: Baseline up to Week 52
Secondary outcomes:
measure: Vector-derived FIX:C activity levels
timeFrame: Baseline up to Week 52
measure: Vector-derived FIX antigen levels
timeFrame: Baseline up to Week 52
measure: Vector shedding of ZS801
timeFrame: Baseline up to Week 52
Other outcomes:
measure: Annualized bleeding rate changes from baseline
timeFrame: Baseline up to Week 52
measure: Annualized FIX consumption changes from baseline
timeFrame: Baseline up to Week 52
measure: Number of target joints
timeFrame: Baseline up to Week 52
measure: Long term factor IX activity up to 10 years after vector infusion
timeFrame: up to 10 years after vector infusion
Locations:
city: Tianjin
country: China
facility: Institute of Hematology & Blood Diseases Hospital
state: Tianjin
Study officials:
affiliation: Institute of Hematology & Blood Diseases Hospital, China
name: Lei Zhang, MD
role: PRINCIPAL_INVESTIGATOR
References: