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

NCT ID: NCT03186677

Last Updated: 2020-11-10

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 11 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-06-03
• Study Completion Date: 2019-02-22

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.

Conditions

Hemophilia B

Keywords

ISU304; previously treated Hemophilia B patients; FIX; Factor IX; CB2679d; Dalcinonacog alfa

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Cohort 1

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

Group Type: EXPERIMENTAL

ISU304/CB2679d/Dalcinonacog alfa 75~150 IU/kg

Intervention Type: BIOLOGICAL

ISU304/CB2679d/Dalcinonacog alfa 75\~150 IU/kg by intravenous or subcutaneous

BeneFIX

Intervention Type: BIOLOGICAL

BeneFIX 75 IU/kg, intravenous administration

Cohort 2

Single intravenous administration of ISU304/CB2679d/Dalcinonacog alfa (75 IU/kg) with 72 hours of observation, followed by single subcutaneous administration of ISU304/CB2679d/Dalcinonacog alfa (75 IU/kg) with 72 hours of observation

Group Type: EXPERIMENTAL

ISU304/CB2679d/Dalcinonacog alfa 75~150 IU/kg

Intervention Type: BIOLOGICAL

ISU304/CB2679d/Dalcinonacog alfa 75\~150 IU/kg by intravenous or subcutaneous

Cohort 3

Single intravenous administration of ISU304/CB2679d/Dalcinonacog alfa (75 IU/kg) with 72 hours of observation, followed by single subcutaneous administration of ISU304/CB2679d/Dalcinonacog alfa (150 IU/kg) with 120 hours of observation

Group Type: EXPERIMENTAL

ISU304/CB2679d/Dalcinonacog alfa 75~150 IU/kg

Intervention Type: BIOLOGICAL

ISU304/CB2679d/Dalcinonacog alfa 75\~150 IU/kg by intravenous or subcutaneous

Cohort 4

One subcutaneous administration of ISU304/CB2679d/Dalcinonacog alfa (150 IU/kg) per day for 6 days with 240 hours of observation

Group Type: EXPERIMENTAL

ISU304/CB2679d/Dalcinonacog alfa 75~150 IU/kg

Intervention Type: BIOLOGICAL

ISU304/CB2679d/Dalcinonacog alfa 75\~150 IU/kg by intravenous or subcutaneous

Cohort 5

One intravenous administration of ISU304/CB2679d/Dalcinonacog alfa (75 IU/kg) followed by subcutaneous administration of ISU304/CB2679d/Dalcinonacog alfa (150 IU/kg) once daily for 9 days with 312 hours of observation

Group Type: EXPERIMENTAL

ISU304/CB2679d/Dalcinonacog alfa 75~150 IU/kg

Intervention Type: BIOLOGICAL

ISU304/CB2679d/Dalcinonacog alfa 75\~150 IU/kg by intravenous or subcutaneous

Interventions

ISU304/CB2679d/Dalcinonacog alfa 75~150 IU/kg

ISU304/CB2679d/Dalcinonacog alfa 75\~150 IU/kg by intravenous or subcutaneous

Intervention Type: BIOLOGICAL

BeneFIX

BeneFIX 75 IU/kg, intravenous administration

Intervention Type: BIOLOGICAL

Other Intervention Names

Dalcinonacog alfa

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

• Minimum Eligible Age: 12 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Catalyst Biosciences

INDUSTRY

Sponsor Role: collaborator

ISU Abxis Co., Ltd.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

ChurWoo You, PhD

Role: PRINCIPAL_INVESTIGATOR

Eulji University Hospital Seo-gu

Locations

Eulji University Hospital

Daejeon, , South Korea

Pusan National Univesity Hospital

Pusan, , South Korea

Yonsei University Medical Center

Seoul, , South Korea

Countries

South Korea

References

Faraj A, Le Moan N, Gorina E, Blouse GE, Knudsen T, Simonsson USH. Model-Informed Support of Dose Selection for Prophylactic Treatment with Dalcinonacog Alfa in Adult and Paediatric Hemophilia B Patients. Adv Ther. 2023 Sep;40(9):3739-3750. doi: 10.1007/s12325-023-02570-6. Epub 2023 Jun 21.

Reference Type: DERIVED

PMID: 37341915 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

ISU304-001/CB2679d

Identifier Type: -

Identifier Source: org_study_id