Dose-escalation Study to Investigate the Safety, PK, and PD of ISU304/CB2679d in Hemophilia B Patients
Condition: Hemophilia B
MeSH terms: Hemophilia A; Hemophilia B
Intervention: ISU304/CB2679d/Dalcinonacog alfa 75~150 IU/kg; BeneFIX
Intervention description: ISU304/CB2679d/Dalcinonacog alfa 75~150 IU/kg by intravenous or subcutaneous; BeneFIX 75 IU/kg, intravenous administration
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Sequential Assignment
Masking: None (Open Label)
Enrollment: 11.0
Sex: All
Minimum age: 12 Years
Maximum age: 65 Years
Healthy volunteers: No
Keywords: ISU304; previously treated Hemophilia B patients; FIX; Factor IX; CB2679d; Dalcinonacog alfa

Summary:

      This study is a phase 1, open-label, multi-center, dose-escalation study to investigate the
      safety, pharmacokinetics and pharmacodynamics of ISU304/CB2679d in previously treated
      hemophilia B patients.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Previously treated male patients with moderate or severe hemophilia B (documented FIX
             activity ≤ 2% and exposed to any FIX product for ≥ 150 exposure days (estimated) at
             the time of screening)

          2. Patients must be 12 to 65 years old at the time of screening

          3. Patients who have discontinued a previously treated FIX product at least 4 days prior
             to the administration of investigational product

          4. HIV negative, or if HIV positive with a CD4 count > 200/μL (documented < 200
             particles/μL or ≤ 400,000 copies/mL) at the time of screening

          5. Voluntary consent to participate in the study

        Exclusion Criteria:

          1. Patients with a history or a family history of FIX inhibitors

          2. Patients with FIX inhibitors (positive result for BeneFIX or ISU304 from inhibitor
             tests) at the time of screening

          3. Patients who have a history of thromboembolic events (myocardial infarction,
             cerebrovascular disease, venous thrombosis, etc.)

          4. Patients with known hypersensitivity, allergy, or anaphylaxis to any FIX product or
             hamster protein

          5. Patients receiving treatment with a FIX product or a bypass agent within 4 half-lives
             for the agent used (at least 96 hours) prior to the administration of the
             investigational product

          6. Patients who have been exposed to long-term administration of immunomodulating agents
             or immunosuppressants such as α-INF or adrenocortical hormones over the past 3 months
             or who are currently receiving or planning to receive such treatment during the study
             period

          7. Patients who have been administered vaccines during the period of 6 months prior to
             the administration of the investigational product or plan to receive vaccines during
             the study period

          8. Patients with any other co-existing bleeding disorder (Von Willebrand disease, etc.)

          9. Patients with positive D-dimer results (≥ 0.5 μg/mL) at the time of screening

         10. Patients with platelet counts less than 100,000/μL at the time of screening

         11. Patients with ALT, AST levels 5 times greater than upper normal limit or total
             bilirubin, serum creatinine levels 2 times greater than upper normal limit at the time
             of screening

         12. Active hepatitis patients who are HBs Ag positive or anti-HCV Ab positive at the time
             of screening

         13. Patients scheduled for surgery during the study period

         14. Patients participated in another study within 30 days before screening or scheduled to
             participate in any other study during the study period