Evaluating ZS801 for treating Hemophilia B in adults

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%.

This study is testing a new treatment called ZS801 to see if it can safely help adults with hemophilia B improve their blood-clotting factor levels.

Quick facts

• Phase: Phase1; Phase2
• Study type: Interventional
• Enrollment: 21 (estimated)
• Ages: 18 Years and up
• Sex: Male
• Sponsor: Institute of Hematology & Blood Diseases Hospital, China (Academic / other)
• Locations: 1 site (Tianjin, Tianjin Municipality)
• Trial ID: NCT05641610 on ClinicalTrials.gov

What this trial studies

This is a non-randomized, open-label, dose-escalation study assessing the safety, tolerability, kinetics, and efficacy of a single intravenous infusion of ZS801 in adult patients with hemophilia B. The trial will enroll 16 patients in a dose-escalation phase, followed by a dose-expansion phase involving 5 additional patients. Participants will undergo screening assessments and will be monitored for 52 weeks post-infusion to evaluate the treatment's effects on blood-clotting factor IX levels and overall safety.

Who should consider this trial

Good fit: Ideal candidates are adult males aged 18 and older with a confirmed diagnosis of hemophilia B and endogenous FIX levels of 2% or less.

Not a fit: Patients who are hypersensitive to any components of the study drug or unable to tolerate immunosuppressants may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could significantly improve the management of hemophilia B by increasing endogenous factor IX levels and reducing bleeding episodes.

How similar studies have performed: While gene therapy approaches for hemophilia have shown promise in other studies, this specific treatment with ZS801 is novel and has not been previously tested.

Eligibility criteria

Inclusion Criteria:

1. Male ≥18 years 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;
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 active hepatitis B infection (HBsAg positive) or active hepatitis C infection (HCVAb 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. AST, ALT, 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 \>1:5;
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.

Where this trial is running

Tianjin, Tianjin Municipality

• Institute of Hematology & Blood Diseases Hospital — Tianjin, Tianjin Municipality, China (Recruiting)

Study contacts

• Principal investigator: Lei Zhang, MD — Institute of Hematology & Blood Diseases Hospital, China
• Study coordinator: Zhang Lei, MD

Conditions Hemophilia B; Gene therapy