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Dose-escalation Study to Investigate the Safety, PK, and PD of ISU304/CB2679d in Hemophilia B Patients

This study is currently recruiting participants.
Verified June 2017 by ISU Abxis Co., Ltd.
Sponsor:
ClinicalTrials.gov Identifier:
NCT03186677
First Posted: June 14, 2017
Last Update Posted: July 28, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Collaborator:
Catalyst Biosciences
Information provided by (Responsible Party):
ISU Abxis Co., Ltd.
  Purpose
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.

Condition Intervention Phase
Hemophilia B Biological: ISU304/CB2679d Biological: BeneFix Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by ISU Abxis Co., Ltd.:

Primary Outcome Measures:
  • incidence of Adverse events (AE) after the administration of investigational products (IP) [ Time Frame: through study completion, an average of 8 days ]
    The incidence of reported AEs (local/systemic/other) after investigational product administration shall be calculated by cohort


Secondary Outcome Measures:
  • Maximum Plasma Concentration (Cmax) [ Time Frame: before the IP administration, 0, up to 120 hours ]
    Cmax analysis by cohort shall be conducted

  • Factor IX inhibitor [ Time Frame: before the IP administration, end of study visit (an average of 8 days) ]
    The analysis of FIX inhibitors (neutralizing antibodies) shall be conducted for each subject by cohort


Estimated Enrollment: 12
Actual Study Start Date: June 3, 2017
Estimated Study Completion Date: May 31, 2018
Estimated Primary Completion Date: March 2, 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Cohort 1
Single intravenous administration of BeneFIX (75 IU/kg) with 72 hours of observation, followed by single intravenous administration of ISU304/CB2679d (75 IU/kg) with 72 hours of observation
Biological: ISU304/CB2679d
ISU304/CB2679d 75~300IU/kg by intravenous or subcutaneous
Biological: BeneFix
BeneFIX 75 IU/kg, intravenous administration
Experimental: Cohort 2
Single intravenous administration of ISU304/CB2679d (75 IU/kg) with 72 hours of observation, followed by single subcutaneous administration of ISU304/CB2679d (75 IU/kg) with 72 hours of observation
Biological: ISU304/CB2679d
ISU304/CB2679d 75~300IU/kg by intravenous or subcutaneous
Experimental: Cohort 3
Single intravenous administration of ISU304/CB2679d (75 IU/kg) with 72 hours of observation, followed by single subcutaneous administration of ISU304/CB2679d (150 IU/kg) with 120 hours of observation
Biological: ISU304/CB2679d
ISU304/CB2679d 75~300IU/kg by intravenous or subcutaneous
Experimental: Cohort 4
Single intravenous administration of ISU304/CB2679d (75 IU/kg) with 72 hours of observation, followed by single subcutaneous administration of ISU304/CB2679d (300 IU/kg) with 120 hours of observation
Biological: ISU304/CB2679d
ISU304/CB2679d 75~300IU/kg by intravenous or subcutaneous
Experimental: Cohort 5
One subcutaneous administration of ISU304/CB2679d (300 IU/kg) per day for 6 days with 144 hours of observation
Biological: ISU304/CB2679d
ISU304/CB2679d 75~300IU/kg by intravenous or subcutaneous

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 in previously treated hemophilia B patients.

This study is comprised of 5 cohorts. Each cohort will receive an identical intravenous administration of 75 IU/kg, with subcutaneous administrations doubling from 75 IU/kg until 300 IU/kg.

During the study period, a subject may be hospitalized to facilitate the collection of blood samples for pharmacokinetic (PK)/pharmacodynamic (PD) analysis. Hospitalization itself will not be considered as a serious adverse event if no adverse event occurs. PK/PD analysis and safety assessments will be conducted for each cohort. 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.

  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   12 Years to 65 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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 mg/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
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03186677


Contacts
Contact: Suyeong Kim, MPharm +82 31 696 4621 andante4me@isu.co.kr

Locations
Korea, Republic of
Eulji University Hospital Recruiting
Daejeon, Korea, Republic of
Contact: Chur Woo You, Dr.         
Pusan National Univesity Hospital Recruiting
Pusan, Korea, Republic of
Contact: Ho-Jin Shin, Dr.         
Yonsei University Medical Center Recruiting
Seoul, Korea, Republic of
Contact: Jin Seok Kim, Dr.         
Sponsors and Collaborators
ISU Abxis Co., Ltd.
Catalyst Biosciences
Investigators
Study Director: June Park, Dr. ISU Abxis Co., Ltd.
  More Information

Responsible Party: ISU Abxis Co., Ltd.
ClinicalTrials.gov Identifier: NCT03186677     History of Changes
Other Study ID Numbers: ISU304-001/CB2679d
First Submitted: May 30, 2017
First Posted: June 14, 2017
Last Update Posted: July 28, 2017
Last Verified: June 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by ISU Abxis Co., Ltd.:
ISU304
previously treated hemophilia B patients
FIX
Factor IX
CB2679d

Additional relevant MeSH terms:
Hemophilia A
Hemophilia B
Blood Coagulation Disorders, Inherited
Blood Coagulation Disorders
Hematologic Diseases
Coagulation Protein Disorders
Hemorrhagic Disorders
Genetic Diseases, Inborn
Genetic Diseases, X-Linked