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

NCT03186677 | Completed Phase 1 Results DMC

• 1 other identifier: ISU304-001/CB2679d
• Study Type: interventional
• Target: 11
• Locations: 1 country
• Sites: 3

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.

Conditions

Hemophilia B

Keywords

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

Outcome Measures

Primary Outcomes (1)

• Number of Adverse Events (AEs) After the Administration of Investigational Products (IP)

  The number of reported AEs (local/systemic/other) after IP administration was calculated by cohort.

  Through study completion, an average of 8 days

Secondary Outcomes (2)

• Maximum Plasma Concentration (Cmax)

  0 to 72 hours for Cohorts 1 to 3, 0 to 120 hours for Cohorts 4 and 5

• Factor IX Inhibitor

  At end of study visit (an average of 8 days)

Study Arms (5)

Cohort 1

EXPERIMENTAL

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

Biological: ISU304/CB2679d/Dalcinonacog alfa 75~150 IU/kg; Biological: BeneFIX

Cohort 2

EXPERIMENTAL

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

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

Cohort 3

EXPERIMENTAL

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

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

Cohort 4

EXPERIMENTAL

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

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

Cohort 5

EXPERIMENTAL

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

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

Interventions

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

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

Also known as: Dalcinonacog alfa

Cohort 1; Cohort 2; Cohort 3; Cohort 4; Cohort 5

BeneFIX BIOLOGICAL

BeneFIX 75 IU/kg, intravenous administration

Cohort 1

Eligibility Criteria

• Age: 12 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)
• Patients must be 12 to 65 years old at the time of screening
• Patients who have discontinued a previously treated FIX product at least 4 days prior to the administration of investigational product
• 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
• Voluntary consent to participate in the study

You may not qualify if:

• Patients with a history or a family history of FIX inhibitors
• Patients with FIX inhibitors (positive result for BeneFIX or ISU304 from inhibitor tests) at the time of screening
• Patients who have a history of thromboembolic events (myocardial infarction, cerebrovascular disease, venous thrombosis, etc.)
• Patients with known hypersensitivity, allergy, or anaphylaxis to any FIX product or hamster protein
• 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
• 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
• 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
• Patients with any other co-existing bleeding disorder (Von Willebrand disease, etc.)
• Patients with positive D-dimer results (≥ 0.5 μg/mL) at the time of screening
• Patients with platelet counts less than 100,000/μL at the time of screening
• 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
• Active hepatitis patients who are HBs Ag positive or anti-HCV Ab positive at the time of screening
• Patients scheduled for surgery during the study period
• Patients participated in another study within 30 days before screening or scheduled to participate in any other study during the study period

Sponsors & Collaborators

• ISU Abxis Co., Ltd.: lead
• Catalyst Biosciences: collaborator

Study Sites (3)

Eulji University Hospital

Daejeon, South Korea

Location

Pusan National Univesity Hospital

Pusan, South Korea

Location

Yonsei University Medical Center

Seoul, South Korea

Location

Related Publications (1)

• 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.

  PMID: 37341915 DERIVED

MeSH Terms

Conditions

Hemophilia B

Interventions

Factor IX

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

Intervention Hierarchy (Ancestors)

Enzyme Precursors; Enzymes and Coenzymes; Blood Coagulation Factors; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Protein Precursors; Biological Factors

Limitations and Caveats

Two subjects who were cousins developed neutralizing antibodies to dalcinonacog alfa in Cohort 5 that did not cross react with wild-type FIX. Both resumed their prior FIX therapy. Five subjects participated in 2 cohorts each.

Results Point of Contact

• Title: Howard Levy, Chief Medical Officer
• Organization: Catalyst Biosciences

hlevy@catbio.com

+1.650.266.6871

Study Officials

• ChurWoo You, PhD

  Eulji University Hospital Seo-gu

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 30, 2017
• First Posted: June 14, 2017
• Study Start: June 3, 2017
• Primary Completion: October 10, 2018
• Study Completion: February 22, 2019
• Last Updated: November 10, 2020
• Results First Posted: November 10, 2020

Record last verified: 2020-10

Data Sharing

• IPD Sharing: Will not share

Locations

KR (3)