Trial Outcomes & Findings for Dose-escalation Study to Investigate the Safety, PK, and PD of ISU304/CB2679d in Hemophilia B Patients (NCT NCT03186677)

NCT ID: NCT03186677

Last Updated: 2020-11-10

Results Overview

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

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

11 participants

Primary outcome timeframe

Through study completion, an average of 8 days

Results posted on

2020-11-10

Participant Flow

There were 11 unique subjects who completed the study; 2 failed screening. Of the 5 subjects in Cohort 4, 1 subject previously participated in Cohort 1 and 2 subjects in Cohort 2. Of the 2 subjects in Cohort 5, 2 subjects previously participated in Cohort 4. As a result, the Safety Analysis Set included 16 subjects. Cohorts were conducted in numerical order.

Participant milestones

Participant milestones
Measure	Period 1, 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	Period 1, 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	Period 1, 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	Period 2, Cohort 4 One subcutaneous administration of ISU304/CB2679d/Dalcinonacog alfa (150 IU/kg) per day for 6 days with 240 hours of observation	Period 2, 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
Period 1 STARTED	3	3	3	0	0
Period 1 COMPLETED	3	3	3	0	0
Period 1 NOT COMPLETED	0	0	0	0	0
Period 2 STARTED	0	0	0	5	2
Period 2 COMPLETED	0	0	0	5	2
Period 2 NOT COMPLETED	0	0	0	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

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.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Cohort 1 n=3 Participants 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	Cohort 2 n=3 Participants 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	Cohort 3 n=3 Participants 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	Cohort 4 n=2 Participants One subcutaneous administration of ISU304/CB2679d/Dalcinonacog alfa (150 IU/kg) per day for 6 days with 240 hours of observation	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	Total n=11 Participants Total of all reporting groups
Age, Categorical <=18 years	1 Participants n=93 Participants • 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.	0 Participants n=4 Participants • 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.	0 Participants n=27 Participants • 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.	0 Participants n=483 Participants • 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.	0 Participants n=36 Participants • 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.	1 Participants n=10 Participants • 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.
Age, Categorical Between 18 and 65 years	2 Participants n=93 Participants • 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.	3 Participants n=4 Participants • 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.	3 Participants n=27 Participants • 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 Participants n=483 Participants • 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.	0 Participants n=36 Participants • 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.	10 Participants n=10 Participants • 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.
Age, Categorical >=65 years	0 Participants n=93 Participants • 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.	0 Participants n=4 Participants • 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.	0 Participants n=27 Participants • 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.	0 Participants n=483 Participants • 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.	0 Participants n=36 Participants • 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.	0 Participants n=10 Participants • 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.
Age, Continuous	29.00 years STANDARD_DEVIATION 16.70 • n=93 Participants	46.33 years STANDARD_DEVIATION 5.69 • n=4 Participants	43.33 years STANDARD_DEVIATION 14.57 • n=27 Participants	50.50 years STANDARD_DEVIATION 3.87 • n=483 Participants	—	41.55 years STANDARD_DEVIATION 13.68 • n=10 Participants
Sex: Female, Male Female	0 Participants n=93 Participants • 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.	0 Participants n=4 Participants • 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.	0 Participants n=27 Participants • 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.	0 Participants n=483 Participants • 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.	0 Participants n=36 Participants • 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.	0 Participants n=10 Participants • 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.
Sex: Female, Male Male	3 Participants n=93 Participants • 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.	3 Participants n=4 Participants • 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.	3 Participants n=27 Participants • 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 Participants n=483 Participants • 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.	0 Participants n=36 Participants • 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.	11 Participants n=10 Participants • 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.
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants	0 Participants n=36 Participants	0 Participants n=10 Participants
Race (NIH/OMB) Asian	3 Participants n=93 Participants	3 Participants n=4 Participants	3 Participants n=27 Participants	2 Participants n=483 Participants	0 Participants n=36 Participants	11 Participants n=10 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants	0 Participants n=36 Participants	0 Participants n=10 Participants
Race (NIH/OMB) Black or African American	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants	0 Participants n=36 Participants	0 Participants n=10 Participants
Race (NIH/OMB) White	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants	0 Participants n=36 Participants	0 Participants n=10 Participants
Race (NIH/OMB) More than one race	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants	0 Participants n=36 Participants	0 Participants n=10 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants	0 Participants n=36 Participants	0 Participants n=10 Participants
Region of Enrollment South Korea	3 Participants n=93 Participants	3 Participants n=4 Participants	3 Participants n=27 Participants	2 Participants n=483 Participants	0 Participants n=36 Participants	11 Participants n=10 Participants

PRIMARY outcome

Timeframe: Through study completion, an average of 8 days

Population: 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.

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

Outcome measures

Outcome measures
Measure	Cohort 1 n=3 Participants 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	Cohort 2 n=3 Participants 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	Cohort 3 n=3 Participants 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	Cohort 4 n=5 Participants One subcutaneous administration of ISU304/CB2679d/Dalcinonacog alfa (150 IU/kg) per day for 6 days with 240 hours of observation	Cohort 5 n=2 Participants 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
Number of Adverse Events (AEs) After the Administration of Investigational Products (IP)	0 adverse events	10 adverse events	10 adverse events	69 adverse events	47 adverse events

SECONDARY outcome

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

Cmax analysis was conducted by cohort as a Factor IX (FIX) potency percent

Outcome measures

Outcome measures
Measure	Cohort 1 n=3 Participants 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	Cohort 2 n=3 Participants 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	Cohort 3 n=3 Participants 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	Cohort 4 n=5 Participants One subcutaneous administration of ISU304/CB2679d/Dalcinonacog alfa (150 IU/kg) per day for 6 days with 240 hours of observation	Cohort 5 n=2 Participants 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
Maximum Plasma Concentration (Cmax) Cmax of ISU304/CB2679d/Dalcinonacog alfa IV	71.10 FIX potency percent Standard Deviation 15.87	100.80 FIX potency percent Standard Deviation 78.00	41.70 FIX potency percent Standard Deviation 7.47	15.34 FIX potency percent Standard Deviation 2.44	23.80 FIX potency percent Standard Deviation 10.04
Maximum Plasma Concentration (Cmax) Cmax of ISU304/CB2679d/Dalcinonacog alfa SC	70.47 FIX potency percent Standard Deviation 16.92	5.30 FIX potency percent Standard Deviation 3.69	5.27 FIX potency percent Standard Deviation 1.16	NA FIX potency percent Standard Deviation NA Cmax calculated for only one treatment and route of administration (subcutaneous) in this cohort.	NA FIX potency percent Standard Deviation NA Cmax calculated for only one treatment and route of administration (subcutaneous) in this cohort.

SECONDARY outcome

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

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.