Hemophilia BPhase 1NCT03186677

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

A Phase 1 study testing ISU304/CB2679d/Dalcinonacog alfa 75~150 IU/kg and BeneFIX in people with Hemophilia B, run by ISU Abxis Co., Ltd. at 3 sites in South Korea.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

Search all trials

Trial 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. Read more about this study

Who is it for?: Ages 12 to 65 years
Conditions the study is for: Hemophilia B
What is being tested?: ISU304/CB2679d/Dalcinonacog alfa 75~150 IU/kg and BeneFIX
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 11 participants
Where: 3 sitesSouth Korea
Study dates: 3 Jun 2017to 22 Feb 2019
Phase: Phase 1
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 12 to 65 years
All sexes
No healthy volunteers
Child, Adult, Older adult

Who may be able to join

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

Who cannot join

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

Show all 14Show fewer

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

Trial locations and contacts

3 sites in 1 country.

South Korea3 sites

Eulji University Hospital
Daejeon
Pusan National Univesity Hospital
Pusan
Yonsei University Medical Center
Seoul

Other trials in South Korea

About this study

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

Read the 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
Being tested: ISU304/CB2679d/Dalcinonacog alfa 75~150 IU/kg, BeneFIX
Keywords: ISU304, previously treated Hemophilia B patients, FIX, Factor IX, CB2679d, Dalcinonacog alfa
Medical subject headings: Hemophilia B

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

ISU304/CB2679d/Dalcinonacog alfa 75~150 IU/kgBiological
Also called Dalcinonacog alfa
ISU304/CB2679d/Dalcinonacog alfa 75~150 IU/kg by intravenous or subcutaneous
BeneFIXBiological
BeneFIX 75 IU/kg, intravenous administration

Study groups in NCT03186677
Study group	Role	What they receive
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 Receives: 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 Receives: 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 Receives: 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 Receives: 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 Receives: Biological: ISU304/CB2679d/Dalcinonacog alfa 75~150 IU/kg

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: Through study completion, an average of 8 days

Secondary outcomes (2)

Maximum Plasma Concentration (Cmax)
Cmax analysis was conducted by cohort as a Factor IX (FIX) potency percent
Measured: 0 to 72 hours for Cohorts 1 to 3, 0 to 120 hours for Cohorts 4 and 5
Factor IX Inhibitor
The presence/absence of Factor IX (FIX) neutralizing antibodies was assessed by ELISA anti-drug assay [Dalcinonacog alfa and BeneFIX) and if positive, a modified Nijmegen assay for each subject by cohort at end of study visit.
Measure description: count of participants with neutralizing antibodies. Bethesda Units >0.6 indicates presence of neutralizing antibodies. 1 BU is defined as a 50% reduction in FIX activity when adding participant plasma to a standard with known FIX activity.
Measured: At end of study visit (an average of 8 days)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

3 Jun 201722 Feb 2019

First posted14 Jun 2017
Study start3 Jun 2017
Primary completion10 Oct 2018
Study completion22 Feb 2019

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Hemophilia BStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1
Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Sequential
Masking: None (open label)
Enrolment: 11 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03186677
Sponsor's protocol ID: ISU304-001/CB2679d
Status last verified: Oct 2020
First submitted: 30 May 2017
Last updated: 10 Nov 2020
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes
FDA-regulated drug: No
FDA-regulated device: No
Individual data sharing: No

Publications

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.
PubMed 37341915

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

Not yet recruiting
Safety of Intraosseous Anaesthesia in Children With Haemophilia
Haemophilia A, Haemophilia B
Active, not recruitingPhase 3
A Study to Evaluate the Efficacy and Safety of Factor IX Gene Therapy With PF-06838435 in Adult Males With Moderately Severe to Severe Hemophilia B
Hemophilia B
Not yet recruitingPhase 1
Lentiviral FIX Gene Therapy
Hemophilia B
RecruitingPhase 3
A Study to Investigate the Efficacy and Safety of Fitusiran Prophylaxis in Male Participants Aged 1 to Less Than 12 Years With Hemophilia A or B
Hemophilia
Not yet recruitingObservational study
A Study to Describe Patient REal-world FitusiRan ExpeRience
Hemophilia A or B

All Hemophilia B trials

Study at a glance

From the registry record, last updated by the sponsor on 10 Nov 2020. Recruitment status is as the sponsor reported it: confirm with the study team.

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
ClinicalTrials.gov ID: NCT03186677
Acronym / sponsor ID: ISU304-001/CB2679d
Conditions: Hemophilia B
Keywords: ISU304, previously treated Hemophilia B patients, FIX, Factor IX, CB2679d, Dalcinonacog alfa
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 11 participants (actual)
Lead sponsor: ISU Abxis Co., Ltd.Industry (pharma, biotech, devices)
Collaborators: Catalyst Biosciences
Study start: 3 Jun 2017 (actual)
Primary completion: 10 Oct 2018 (actual)
Study completion: 22 Feb 2019 (actual)
First posted: 14 Jun 2017 (actual)
Results: Posted 10 Nov 2020

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

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.

Study design

Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Sequential
Masking: None (open label)
Number of arms: 5

Arm	Type	Receives
Cohort 1	Experimental	Biological: ISU304/CB2679d/Dalcinonacog alfa 75~150 IU/kg, Biological: BeneFIXSingle 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
Cohort 2	Experimental	Biological: ISU304/CB2679d/Dalcinonacog alfa 75~150 IU/kgSingle 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
Cohort 3	Experimental	Biological: ISU304/CB2679d/Dalcinonacog alfa 75~150 IU/kgSingle 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
Cohort 4	Experimental	Biological: ISU304/CB2679d/Dalcinonacog alfa 75~150 IU/kgOne subcutaneous administration of ISU304/CB2679d/Dalcinonacog alfa (150 IU/kg) per day for 6 days with 240 hours of observation
Cohort 5	Experimental	Biological: ISU304/CB2679d/Dalcinonacog alfa 75~150 IU/kgOne 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

Who may qualify

Ages: 12 to 65 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Child, Adult, Older adult

Key inclusion criteria (5 listed)

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

Key exclusion criteria (14 listed)

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

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
ISU304/CB2679d/Dalcinonacog alfa 75~150 IU/kgAlso: Dalcinonacog alfaISU304/CB2679d/Dalcinonacog alfa 75~150 IU/kg by intravenous or subcutaneous	Biological	Cohort 1, Cohort 2, Cohort 3, Cohort 4, Cohort 5
BeneFIXBeneFIX 75 IU/kg, intravenous administration	Biological	Cohort 1

Primary outcome

Number of Adverse Events (AEs) After the Administration of Investigational Products (IP)
Time frame: Through study completion, an average of 8 days
The number of reported AEs (local/systemic/other) after IP administration was calculated by cohort.

2 secondary outcomes

Maximum Plasma Concentration (Cmax)
Time frame: 0 to 72 hours for Cohorts 1 to 3, 0 to 120 hours for Cohorts 4 and 5
Factor IX Inhibitor
Time frame: At end of study visit (an average of 8 days)

Results and safety

Results posted to the registry on 10 Nov 2020, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Period 1, Cohort 1	3	3
Period 1, Cohort 2	3	3
Period 1, Cohort 3	3	3
Period 2, Cohort 4	0	0
Period 2, Cohort 5	0	0

Primary outcome: Number of Adverse Events (AEs) After the Administration of Investigational Products (IP)

Time frame: Through study completion, an average of 8 days. Number. Unit: adverse events

Measure	Cohort 1 n = 3	Cohort 2 n = 3	Cohort 3 n = 3	Cohort 4 n = 5	Cohort 5 n = 2
Value	0	10	10	69	47

Population analysed: There were 13 unique subjects in the study: 11 completed study and 2 failed screening. Of the 11 individuals who completed the study, 5 were in multiple cohorts. 16 subjects were included in the Safety Analysis Set across 5 cohorts.

2 secondary outcomes are reported in the full results.

Adverse events

Time frame: For 7 to 15 days depending on the cohort: Cohort 1 (7 days), Cohort 2 (7 days), Cohort 3 (9 days), Cohort 4 (10 days), Cohort 5 (15 days). Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Cohort 1	0 of 3 (0%)	0 of 3 (0%)	0 of 3
Cohort 2	0 of 3 (0%)	3 of 3 (100%)	0 of 3
Cohort 3	0 of 3 (0%)	3 of 3 (100%)	0 of 3
Cohort 4	0 of 5 (0%)	5 of 5 (100%)	0 of 5
Cohort 5	0 of 2 (0%)	2 of 2 (100%)	0 of 2

Limitations and caveats (from the sponsor): 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.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 10 Nov 2020.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 37341915Faraj 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.
Individual participant dataSharing planned: No

Related trials for Hemophilia B

Not yet recruiting
Safety of Intraosseous Anaesthesia in Children With Haemophilia
Haemophilia A, Haemophilia B
Active, not recruitingPhase 3
A Study to Evaluate the Efficacy and Safety of Factor IX Gene Therapy With PF-06838435 in Adult Males With Moderately Severe to Severe Hemophilia B
Hemophilia B
Not yet recruitingPhase 1
Lentiviral FIX Gene Therapy
Hemophilia B
RecruitingPhase 3
A Study to Investigate the Efficacy and Safety of Fitusiran Prophylaxis in Male Participants Aged 1 to Less Than 12 Years With Hemophilia A or B
Hemophilia
Not yet recruitingObservational study
A Study to Describe Patient REal-world FitusiRan ExpeRience
Hemophilia A or B

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

ChurWoo You, PhD principal investigator

Eulji University Hospital Seo-gu

3 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing ISU304/CB2679d/Dalcinonacog alfa 75~150 IU/kg and BeneFIX in people with Hemophilia B, run by ISU Abxis Co., Ltd. at 3 sites in South Korea.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 10 Nov 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites in South Korea. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 10 Nov 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Adverse Events (AEs) After the Administration of Investigational Products (IP) (time frame: Through study completion, an average of 8 days). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03186677, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Nov 2020.