Brief Title
Dose-escalation Study to Investigate the Safety, PK, and PD of ISU304/CB2679d in Hemophilia B Patients
Official Title
A Phase 1, Open-label, Multi-center, Dose-escalation Study to Investigate the Safety, Pharmacokinetics and Pharmacodynamics of ISU304 in Previously Treated Hemophilia B Patients
Brief 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.
Detailed Description
This study is a phase 1, open-label, multi-center, dose-escalation study to investigate the
safety, pharmacokinetics, and pharmacodynamics of ISU304/CB2679d/Dalcinonacog alfa in
previously treated Hemophilia B patients.
This study is comprised of 5 cohorts. Each cohort may receive an intravenous administration
of 75 IU/kg, with subcutaneous administrations from 75 IU/kg to 150 IU/kg.
During the study period, a subject may be hospitalized to facilitate the collection of blood
samples for pharmacokinetic (PK)/pharmacodynamic (PD) analysis. The Data Safety Monitoring
Board (DSMB) and Data Monitoring Committee (DMC) will be operated after the end of Cohorts 1
to 4. These committees will monitor the PK/PD and safety data from each cohort to determine
the continuation of next cohort (Cohorts 2 to 5), target dose, and blood sampling period for
PK/PD (including timing of collection). Additional subjects may be enrolled in all cohorts or
cohorts may be canceled depending on the results of PK/PD analysis. A cohort of subcutaneous
dosing at 300 IU/kg was cancelled as single-dose PK is uninformative.
Study Phase
Phase 1
Study Type
Interventional
Primary Outcome
Number of Adverse Events (AEs) After the Administration of Investigational Products (IP)
Secondary Outcome
Maximum Plasma Concentration (Cmax)
Condition
Hemophilia B
Intervention
ISU304/CB2679d/Dalcinonacog alfa 75~150 IU/kg
Study Arms / Comparison Groups
Cohort 1
Description: Single intravenous administration of BeneFIX (75 IU/kg) with 72 hours of observation, followed by single intravenous administration of ISU304/CB2679d/Dalcinonacog alfa (75 IU/kg) with 72 hours of observation
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Biological
Estimated Enrollment
11
Start Date
June 3, 2017
Completion Date
February 22, 2019
Primary Completion Date
October 10, 2018
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
Gender
All
Ages
12 Years - 65 Years
Accepts Healthy Volunteers
No
Contacts
ChurWoo You, PhD, ,
Location Countries
Korea, Republic of
Location Countries
Korea, Republic of
Administrative Informations
NCT ID
NCT03186677
Organization ID
ISU304-001/CB2679d
Responsible Party
Sponsor
Study Sponsor
ISU Abxis Co., Ltd.
Collaborators
Catalyst Biosciences
Study Sponsor
ChurWoo You, PhD, Principal Investigator, Eulji University Hospital Seo-gu
Verification Date
October 2020