A Study to Evaluate the Safety and Efficacy of ZS801 in Adult Hemophilia B Patients

NCT05641610 | Recruiting Phase 1

• 1 other identifier: IIT2021057（ZS801-01）
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 1

Brief Summary

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%.

Conditions

Hemophilia B

Keywords

Hemophilia B; Gene therapy

Outcome Measures

Primary Outcomes (5)

• 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

• 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

• 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

• 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

• 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 Outcomes (3)

• Vector-derived FIX activity levels

  Baseline up to Week 52

• Vector-derived FIX antigen levels

  Baseline up to Week 52

• Vector shedding of ZS801

  Baseline up to Week 52

Other Outcomes (3)

• Annualized bleeding rate changes from baseline

  Baseline up to Week 52

• Annualized FIX consumption changes from baseline

  Baseline up to Week 52

• Number of target joints

  Baseline up to Week 52

Study Arms (1)

ZS801

EXPERIMENTAL

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

Genetic: ZS801

Interventions

ZS801 GENETIC

A novel, bioengineered adeno-associated viral (AAV) vector carrying human factor IX variant. The dose levels are as follows: 2.0×10\^12vg/kg, 5.0×10\^12vg/kg, 1.0×10\^13vg/kg.

ZS801

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male ≥18 years 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;
• 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.

You may not qualify if:

• 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 active hepatitis B infection (HBsAg positive) or active hepatitis C infection (HCVAb 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;
• AST, ALT, alkaline phosphatase\>2×ULN;

Sponsors & Collaborators

• Institute of Hematology & Blood Diseases Hospital, China: lead

Study Sites (1)

Institute of Hematology & Blood Diseases Hospital

Tianjin, Tianjin Municipality, 300020, China

RECRUITING

MeSH Terms

Conditions

Hemophilia B

Condition Hierarchy (Ancestors)

Blood Coagulation Disorders, Inherited; Blood Coagulation Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Coagulation Protein Disorders; Hemorrhagic Disorders; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Genetic Diseases, X-Linked

Study Officials

• Lei Zhang, MD

  Institute of Hematology & Blood Diseases Hospital, China

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Zhang Lei, MD

CONTACT

+86 022-23909240; zhanglei1@ihcams.ac.cn

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Hemophilia B patients

Study Record Dates

• First Submitted: November 25, 2022
• First Posted: December 7, 2022
• Study Start: February 16, 2022
• Primary Completion: December 1, 2025
• Study Completion (Estimated): December 1, 2028
• Last Updated: February 24, 2025

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL
• Time Frame: IPD will be shared with other researchers when ZS801 is fully approved
• Access Criteria: IPD will be shared with other researchers when ZS801 is fully approved

Locations

CN (1)