Trial Outcomes & Findings for Study of Next-Generation Recombinant Factor IX Variant in Adult Subjects With Hemophilia B (NCT NCT03995784)
NCT ID: NCT03995784
Last Updated: 2021-08-09
Results Overview
Subjects who achieved a FIX activity level ≥12% during the treatment period in the PK Population
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
6 participants
Primary outcome timeframe
Days 7, 14, 21, 28, 29
Results posted on
2021-08-09
Participant Flow
11 subjects were screened in the study, but 4 subjects failed screening due to inclusion/exclusion criteria not met and 1 subject was screened, but withdrew consent before receiving any study medication. These 5 subjects were considered not enrolled into the Treatment Period, and the remaining 6 were considered enrolled into the Treatment Period. Of those 6 enrolled into the Treatment Period, 5 subjects completed the study. The 6 subjects enrolled comprise the Overall Subjects/Population.
Participant milestones
| Measure |
Overall Subjects
Subjects were dosed with a single intravenous injection dose of 50 IU/kg coagulation Factor IX variant (CB2679d/Dalcinonacog alfa) and then daily subcutaneous doses of 100 IU/kg coagulation Factor IX variant (CB2679d/Dalcinonacog alfa) for 28 days
|
|---|---|
|
Overall Study
STARTED
|
6
|
|
Overall Study
COMPLETED
|
5
|
|
Overall Study
NOT COMPLETED
|
1
|
Reasons for withdrawal
| Measure |
Overall Subjects
Subjects were dosed with a single intravenous injection dose of 50 IU/kg coagulation Factor IX variant (CB2679d/Dalcinonacog alfa) and then daily subcutaneous doses of 100 IU/kg coagulation Factor IX variant (CB2679d/Dalcinonacog alfa) for 28 days
|
|---|---|
|
Overall Study
One subject discontinued on Day 7 due to injection site reactions after Day 1, 2, and 3 doses
|
1
|
Baseline Characteristics
Study of Next-Generation Recombinant Factor IX Variant in Adult Subjects With Hemophilia B
Baseline characteristics by cohort
| Measure |
Overall Subjects
n=6 Participants
All subjects in the Safety Population received study treatment
|
|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
6 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=5 Participants
|
|
Sex: Female, Male
Female
|
0 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
6 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
6 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
5 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Days 7, 14, 21, 28, 29Population: PK population. One subject not included in the PK population discontinued the study on Day 7 and had an activity level \>12%
Subjects who achieved a FIX activity level ≥12% during the treatment period in the PK Population
Outcome measures
| Measure |
Overall Subjects
n=5 Participants
All subjects in the PK population
|
Change From Baseline (%)
Change from Baseline in values of FIX activity levels during study
|
|---|---|---|
|
Number of Subjects Who Achieved FIX Level ≥12%
Day 7
|
3 Participants
|
—
|
|
Number of Subjects Who Achieved FIX Level ≥12%
Day 14
|
4 Participants
|
—
|
|
Number of Subjects Who Achieved FIX Level ≥12%
Day 21
|
4 Participants
|
—
|
|
Number of Subjects Who Achieved FIX Level ≥12%
Day 28
|
4 Participants
|
—
|
|
Number of Subjects Who Achieved FIX Level ≥12%
Day 29
|
5 Participants
|
—
|
SECONDARY outcome
Timeframe: Screening, Day 1 (IV Pre-dose, SC Dose), Day 2, 3, 7, 14, 21, 28, 29, 30, 31, 32, 33, and End of Study. End of Study is the average of each subject's last recorded assessment (between Days 29 to 33).Population: PK Population. 1 subject received a higher IV dose than allowed per protocol (150 IU/kg) at Day 1 thus this subject's values at Day 1 (SC Dose), Day 2, \& Day 3 were excluded from this analysis \& the total number of participants was lowered by 1 at these timepoints. Additionally, mean (standard deviation) for the maximum change from baseline in the FIX activity level (%) during SC dosing was calculated by excluding actual values at Day 1 IV dose, Day 1 SC dose, Day 2 \& Day 3 for all 6 subjects.
FIX Activity Levels measured by percent activity. Baseline was defined as the lowest assessment before the first administration of study drug. Maximum change from baseline was calculated as the maximum of the changes from baseline over all visits during treatment period. FIX activity level below the limit of quantification (BLQ) were set to zero. In case of retest, the average of the different test results were considered for the summary analyses. 1 subject received a higher IV dose than allowed per protocol (150 IU/kg) at Day 1 thus this subject's values at Day 1 (SC Dose), Day 2, \& Day 3 were excluded from this analysis \& the total number of participants was lowered by 1 at these timepoints. Additionally, mean (standard deviation) for the maximum change from baseline in the FIX activity level (%) during SC dosing was calculated by excluding actual values at Day 1 IV dose, Day 1 SC dose, Day 2 \& Day 3 for all 6 subjects.
Outcome measures
| Measure |
Overall Subjects
n=5 Participants
All subjects in the PK population
|
Change From Baseline (%)
n=5 Participants
Change from Baseline in values of FIX activity levels during study
|
|---|---|---|
|
FIX Activity Levels (Actual and Change From Baseline) in All Subjects
Screening
|
0.24 % (percent) activity
Standard Deviation 0.5367
|
—
|
|
FIX Activity Levels (Actual and Change From Baseline) in All Subjects
Day 1, IV Predose
|
11.54 % (percent) activity
Standard Deviation 20.3775
|
—
|
|
FIX Activity Levels (Actual and Change From Baseline) in All Subjects
Day 1, SC Dose
|
25.538 % (percent) activity
Standard Deviation 9.2245
|
25.238 % (percent) activity
Standard Deviation 8.7156
|
|
FIX Activity Levels (Actual and Change From Baseline) in All Subjects
Day 2
|
15.05 % (percent) activity
Standard Deviation 4.7177
|
14.75 % (percent) activity
Standard Deviation 4.1589
|
|
FIX Activity Levels (Actual and Change From Baseline) in All Subjects
Day 3
|
13.8 % (percent) activity
Standard Deviation 2.7362
|
13.5 % (percent) activity
Standard Deviation 2.5153
|
|
FIX Activity Levels (Actual and Change From Baseline) in All Subjects
Day 7
|
13.64 % (percent) activity
Standard Deviation 4.7141
|
13.4 % (percent) activity
Standard Deviation 4.7974
|
|
FIX Activity Levels (Actual and Change From Baseline) in All Subjects
Day 14
|
18.66 % (percent) activity
Standard Deviation 7.7986
|
18.42 % (percent) activity
Standard Deviation 7.5301
|
|
FIX Activity Levels (Actual and Change From Baseline) in All Subjects
Day 21
|
18.74 % (percent) activity
Standard Deviation 6.5328
|
18.5 % (percent) activity
Standard Deviation 6.1895
|
|
FIX Activity Levels (Actual and Change From Baseline) in All Subjects
Day 28
|
19.92 % (percent) activity
Standard Deviation 6.6571
|
19.68 % (percent) activity
Standard Deviation 6.3622
|
|
FIX Activity Levels (Actual and Change From Baseline) in All Subjects
Day 29
|
19.44 % (percent) activity
Standard Deviation 4.385
|
19.2 % (percent) activity
Standard Deviation 4.1905
|
|
FIX Activity Levels (Actual and Change From Baseline) in All Subjects
Day 30
|
14.92 % (percent) activity
Standard Deviation 3.4354
|
14.68 % (percent) activity
Standard Deviation 3.2653
|
|
FIX Activity Levels (Actual and Change From Baseline) in All Subjects
Day 31
|
12.06 % (percent) activity
Standard Deviation 1.8119
|
11.82 % (percent) activity
Standard Deviation 1.4721
|
|
FIX Activity Levels (Actual and Change From Baseline) in All Subjects
Day 32
|
8.763 % (percent) activity
Standard Deviation 2.7348
|
8.463 % (percent) activity
Standard Deviation 2.3085
|
|
FIX Activity Levels (Actual and Change From Baseline) in All Subjects
Day 33
|
8.288 % (percent) activity
Standard Deviation 1.7148
|
7.988 % (percent) activity
Standard Deviation 1.1707
|
|
FIX Activity Levels (Actual and Change From Baseline) in All Subjects
End of Study
|
0.32 % (percent) activity
Standard Deviation 0.7155
|
0.08 % (percent) activity
Standard Deviation 0.1789
|
|
FIX Activity Levels (Actual and Change From Baseline) in All Subjects
SC Maximum change from baseline during SC dosing
|
—
|
21.183 % (percent) activity
Standard Deviation 4.4723
|
SECONDARY outcome
Timeframe: From date of first dose of CB2679d until date of first occurrence of clinical event, assessed up to treatment Day 28. PK sampling was conducted on Day 1 (IV pre-dose -5 min, SC 30 min post IV dose, hour 7 +/- 1 hour) and Day 2 (hour 24 +/- 1 hour).Population: PK Population
Summary of Pharmacokinetic Parameters - AUC Infinity Observation and AUC to Last Non-zero Concentration
Outcome measures
| Measure |
Overall Subjects
n=5 Participants
All subjects in the PK population
|
Change From Baseline (%)
Change from Baseline in values of FIX activity levels during study
|
|---|---|---|
|
Pharmacokinetic (PK) Analysis - AUC
AUC Infinity Observation
|
126.0306 IU/dL*day
Standard Deviation 26.80093
|
—
|
|
Pharmacokinetic (PK) Analysis - AUC
AUC to Last Non-zero Concentration
|
75.415 IU/dL*day
Standard Deviation 17.22908
|
—
|
SECONDARY outcome
Timeframe: From date of first dose of CB2679d until date of first occurrence of clinical event, assessed up to treatment Day 28. PK sampling was conducted on Day 1 (IV pre-dose -5 min, SC 30 min post IV dose, hour 7 +/- 1 hour) and Day 2 (hour 24 +/- 1 hour).Population: PK Population
Summary of PK Parameters - Clearance
Outcome measures
| Measure |
Overall Subjects
n=5 Participants
All subjects in the PK population
|
Change From Baseline (%)
Change from Baseline in values of FIX activity levels during study
|
|---|---|---|
|
PK Analysis - Clearance
|
0.8191544 dL/day/kg
Standard Deviation 0.15349536
|
—
|
SECONDARY outcome
Timeframe: From date of first dose of CB2679d until date of first occurrence of clinical event, assessed up to treatment Day 28. PK sampling was conducted on Day 1 (IV pre-dose -5 min, SC 30 min post IV dose, hour 7 +/- 1 hour) and Day 2 (hour 24 +/- 1 hour).Population: PK Population
Summary of PK Parameters - Maximum Concentration during SC dosing
Outcome measures
| Measure |
Overall Subjects
n=5 Participants
All subjects in the PK population
|
Change From Baseline (%)
Change from Baseline in values of FIX activity levels during study
|
|---|---|---|
|
PK Analysis - Maximum Concentration During SC Dosing
|
20.74 IU/dL
Standard Deviation 5.58
|
—
|
SECONDARY outcome
Timeframe: From date of first dose of CB2679d until date of first occurrence of clinical event, assessed up to treatment Day 28. PK sampling was conducted on Day 1 (IV pre-dose -5 min, SC 30 min post IV dose, hour 7 +/- 1 hour) and Day 2 (hour 24 +/- 1 hour).Population: PK Population
Summary of PK Parameters - Half-Life-1(alpha), Half-Life-1(beta), and Mean Residence Time
Outcome measures
| Measure |
Overall Subjects
n=2 Participants
All subjects in the PK population
|
Change From Baseline (%)
Change from Baseline in values of FIX activity levels during study
|
|---|---|---|
|
PK Analysis - Half-Life and Residence Time
Half-Life-1(alpha)
|
5.32395 days
Standard Deviation 3.049964
|
—
|
|
PK Analysis - Half-Life and Residence Time
Half-Life-1(beta)
|
3.87172 days
Standard Deviation 1.132563
|
—
|
|
PK Analysis - Half-Life and Residence Time
Mean Residence Time
|
6.1572 days
Standard Deviation 1.609332
|
—
|
SECONDARY outcome
Timeframe: From date of first dose of CB2679d until date of first occurrence of clinical event, assessed up to treatment Day 28. PK sampling was conducted on Day 1 (IV pre-dose -5 min, SC 30 min post IV dose, hour 7 +/- 1 hour) and Day 2 (hour 24 +/- 1 hour).Population: PK Population
Summary of PK Parameters - Volume of Distribution at Steady-State Observed
Outcome measures
| Measure |
Overall Subjects
n=5 Participants
All subjects in the PK population
|
Change From Baseline (%)
Change from Baseline in values of FIX activity levels during study
|
|---|---|---|
|
PK Analysis - Volume of Distribution at Steady-State Observed
|
5.00736 dL/kg
Standard Deviation 1.542769
|
—
|
SECONDARY outcome
Timeframe: From date of first dose of CB2679d until date of first occurrence of clinical event, assessed up to treatment Day 28Population: Safety Population
Rate of occurrence of clinical thrombotic event not attributable to another cause
Outcome measures
| Measure |
Overall Subjects
n=6 Participants
All subjects in the PK population
|
Change From Baseline (%)
Change from Baseline in values of FIX activity levels during study
|
|---|---|---|
|
Occurrence of Clinical Thrombotic Event
|
0 Participants
|
—
|
SECONDARY outcome
Timeframe: From date of first dose of CB2679d until date of first occurrence of clinical event, assessed up to treatment Day 28Population: Safety Population
Rate of occurrence of an antibody response to CB2679d and cross-reactive with wild-type recombinant coagulation FIX
Outcome measures
| Measure |
Overall Subjects
n=6 Participants
All subjects in the PK population
|
Change From Baseline (%)
Change from Baseline in values of FIX activity levels during study
|
|---|---|---|
|
Occurrence of an Antibody Response
Confirmed Antidrug Antibody (ADA) to DalcA
|
2 Participants
|
—
|
|
Occurrence of an Antibody Response
Neutralizing antibody to DalcA
|
0 Participants
|
—
|
SECONDARY outcome
Timeframe: Screening, Day 1 (IV Pre-dose, SC Dose), Day 2, 3, 7, 14, 21, 28, 29, 30, 31, 32, 33, and End of Study. End of Study is the average of each subject's last recorded assessment (between Days 29 to 33).Population: Pharmacodynamic Population
Evaluation of the levels of thrombogenicity markers of a subcutaneous regimen of CB2679d
Outcome measures
| Measure |
Overall Subjects
n=5 Participants
All subjects in the PK population
|
Change From Baseline (%)
n=5 Participants
Change from Baseline in values of FIX activity levels during study
|
|---|---|---|
|
Thrombogenicity Assessment - Fibrinogen
Fibrinogen - Day 30
|
306.0 mg/dL
Standard Deviation 62.38
|
0.4 mg/dL
Standard Deviation 127.73
|
|
Thrombogenicity Assessment - Fibrinogen
Fibrinogen - Screening
|
300.4 mg/dL
Standard Deviation 64.77
|
—
|
|
Thrombogenicity Assessment - Fibrinogen
Fibrinogen - Day 1, IV Pre-dose
|
305.6 mg/dL
Standard Deviation 73.53
|
—
|
|
Thrombogenicity Assessment - Fibrinogen
Fibrinogen - Day 1, SC Dose
|
326.4 mg/dL
Standard Deviation 79.04
|
20.8 mg/dL
Standard Deviation 12.50
|
|
Thrombogenicity Assessment - Fibrinogen
Fibrinogen - Day 2
|
296.2 mg/dL
Standard Deviation 72.29
|
-9.4 mg/dL
Standard Deviation 18.04
|
|
Thrombogenicity Assessment - Fibrinogen
Fibrinogen - Day 3
|
299.2 mg/dL
Standard Deviation 65.98
|
-6.4 mg/dL
Standard Deviation 33.58
|
|
Thrombogenicity Assessment - Fibrinogen
Fibrinogen - Day 7
|
285.8 mg/dL
Standard Deviation 52.64
|
-19.8 mg/dL
Standard Deviation 71.92
|
|
Thrombogenicity Assessment - Fibrinogen
Fibrinogen - Day 14
|
272.2 mg/dL
Standard Deviation 42.81
|
-33.4 mg/dL
Standard Deviation 87.16
|
|
Thrombogenicity Assessment - Fibrinogen
Fibrinogen - Day 21
|
283.6 mg/dL
Standard Deviation 55.68
|
-22.0 mg/dL
Standard Deviation 78.19
|
|
Thrombogenicity Assessment - Fibrinogen
Fibrinogen - Day 28
|
314.4 mg/dL
Standard Deviation 87.21
|
8.8 mg/dL
Standard Deviation 149.17
|
|
Thrombogenicity Assessment - Fibrinogen
Fibrinogen - Day 29
|
313.2 mg/dL
Standard Deviation 73.31
|
7.6 mg/dL
Standard Deviation 141.32
|
|
Thrombogenicity Assessment - Fibrinogen
Fibrinogen - Day 31
|
313.8 mg/dL
Standard Deviation 76.40
|
8.2 mg/dL
Standard Deviation 138.79
|
|
Thrombogenicity Assessment - Fibrinogen
Fibrinogen - Day 32
|
300.8 mg/dL
Standard Deviation 114.93
|
22.8 mg/dL
Standard Deviation 107.82
|
|
Thrombogenicity Assessment - Fibrinogen
Fibrinogen - Day 33
|
342.8 mg/dL
Standard Deviation 68.75
|
64.8 mg/dL
Standard Deviation 87.93
|
|
Thrombogenicity Assessment - Fibrinogen
Fibrinogen - End of Study
|
285.2 mg/dL
Standard Deviation 30.60
|
-20.4 mg/dL
Standard Deviation 101.45
|
|
Thrombogenicity Assessment - Fibrinogen
Fibrinogen - Maximum change from baseline during dosing
|
—
|
-10.4 mg/dL
Standard Deviation 103.83
|
SECONDARY outcome
Timeframe: Screening, Day 1 (IV Pre-dose, SC Dose), Day 2, 3, 7, 14, 21, 28, 29, 30, 31, 32, 33, and End of Study. End of Study is the average of each subject's last recorded assessment (between Days 29 to 33).Population: Pharmacodynamic Population
Evaluation of the levels of thrombogenicity markers of a subcutaneous regimen of CB2679d
Outcome measures
| Measure |
Overall Subjects
n=5 Participants
All subjects in the PK population
|
Change From Baseline (%)
n=5 Participants
Change from Baseline in values of FIX activity levels during study
|
|---|---|---|
|
Thrombogenicity Assessment - D-Dimer
D-Dimer - Screening
|
169.6 ug/L
Standard Deviation 155.63
|
—
|
|
Thrombogenicity Assessment - D-Dimer
D-Dimer - Day 1, IV Pre-dose
|
218.6 ug/L
Standard Deviation 153.78
|
—
|
|
Thrombogenicity Assessment - D-Dimer
D-Dimer - Day 1, SC Dose
|
209.6 ug/L
Standard Deviation 183.77
|
-9.0 ug/L
Standard Deviation 58.71
|
|
Thrombogenicity Assessment - D-Dimer
D-Dimer - Day 2
|
654.6 ug/L
Standard Deviation 426.46
|
436.0 ug/L
Standard Deviation 427.86
|
|
Thrombogenicity Assessment - D-Dimer
D-Dimer - Day 3
|
680.6 ug/L
Standard Deviation 405.82
|
462.0 ug/L
Standard Deviation 378.00
|
|
Thrombogenicity Assessment - D-Dimer
D-Dimer - Day 7
|
761.0 ug/L
Standard Deviation 550.10
|
542.4 ug/L
Standard Deviation 572.80
|
|
Thrombogenicity Assessment - D-Dimer
D-Dimer - Day 14
|
969.4 ug/L
Standard Deviation 993.15
|
750.8 ug/L
Standard Deviation 1053.87
|
|
Thrombogenicity Assessment - D-Dimer
D-Dimer - Day 21
|
772.6 ug/L
Standard Deviation 999.62
|
554.0 ug/L
Standard Deviation 1069.36
|
|
Thrombogenicity Assessment - D-Dimer
D-Dimer - Day 28
|
590.8 ug/L
Standard Deviation 311.30
|
372.2 ug/L
Standard Deviation 410.31
|
|
Thrombogenicity Assessment - D-Dimer
D-Dimer - Day 29
|
675.6 ug/L
Standard Deviation 845.00
|
457.0 ug/L
Standard Deviation 920.85
|
|
Thrombogenicity Assessment - D-Dimer
D-Dimer - Day 30
|
313.4 ug/L
Standard Deviation 275.43
|
94.8 ug/L
Standard Deviation 343.02
|
|
Thrombogenicity Assessment - D-Dimer
D-Dimer - Day 31
|
293.8 ug/L
Standard Deviation 242.76
|
75.2 ug/L
Standard Deviation 314.13
|
|
Thrombogenicity Assessment - D-Dimer
D-Dimer - Day 32
|
364.5 ug/L
Standard Deviation 371.95
|
143.5 ug/L
Standard Deviation 433.31
|
|
Thrombogenicity Assessment - D-Dimer
D-Dimer - Day 33
|
390.5 ug/L
Standard Deviation 323.83
|
169.5 ug/L
Standard Deviation 404.25
|
|
Thrombogenicity Assessment - D-Dimer
D-Dimer - End of Study
|
212.8 ug/L
Standard Deviation 177.26
|
-5.8 ug/L
Standard Deviation 242.12
|
|
Thrombogenicity Assessment - D-Dimer
D-Dimer - Maximum change from baseline during dosing
|
—
|
1088.0 ug/L
Standard Deviation 921.99
|
SECONDARY outcome
Timeframe: Screening, Day 1 (IV Pre-dose, SC Dose), Day 2, 3, 7, 14, 21, 28, 29, 30, 31, 32, 33, and End of Study. End of Study is the average of each subject's last recorded assessment (between Days 29 to 33).Population: Pharmacodynamic Population
Evaluation of the levels of thrombogenicity markers of a subcutaneous regimen of CB2679d
Outcome measures
| Measure |
Overall Subjects
n=5 Participants
All subjects in the PK population
|
Change From Baseline (%)
n=5 Participants
Change from Baseline in values of FIX activity levels during study
|
|---|---|---|
|
Thrombogenicity Assessment - Prothrombin Fragments 1 + 2
Prothrombin Fragments 1 + 2 - Screening
|
151.2 pmol/L
Standard Deviation 55.63
|
—
|
|
Thrombogenicity Assessment - Prothrombin Fragments 1 + 2
Prothrombin Fragments 1 + 2 - Day 1, IV Pre-dose
|
187.8 pmol/L
Standard Deviation 126.73
|
—
|
|
Thrombogenicity Assessment - Prothrombin Fragments 1 + 2
Prothrombin Fragments 1 + 2 - Day 1, SC Dose
|
195.2 pmol/L
Standard Deviation 141.90
|
7.4 pmol/L
Standard Deviation 58.11
|
|
Thrombogenicity Assessment - Prothrombin Fragments 1 + 2
Prothrombin Fragments 1 + 2 - Day 2
|
171.4 pmol/L
Standard Deviation 75.79
|
-16.4 pmol/L
Standard Deviation 93.75
|
|
Thrombogenicity Assessment - Prothrombin Fragments 1 + 2
Prothrombin Fragments 1 + 2 - Day 3
|
158.8 pmol/L
Standard Deviation 63.08
|
-29.0 pmol/L
Standard Deviation 88.88
|
|
Thrombogenicity Assessment - Prothrombin Fragments 1 + 2
Prothrombin Fragments 1 + 2 - Day 7
|
203.2 pmol/L
Standard Deviation 110.30
|
15.4 pmol/L
Standard Deviation 129.60
|
|
Thrombogenicity Assessment - Prothrombin Fragments 1 + 2
Prothrombin Fragments 1 + 2 - Day 14
|
192.8 pmol/L
Standard Deviation 99.38
|
5.0 pmol/L
Standard Deviation 130.70
|
|
Thrombogenicity Assessment - Prothrombin Fragments 1 + 2
Prothrombin Fragments 1 + 2 - Day 21
|
126.6 pmol/L
Standard Deviation 39.63
|
-61.2 pmol/L
Standard Deviation 127.21
|
|
Thrombogenicity Assessment - Prothrombin Fragments 1 + 2
Prothrombin Fragments 1 + 2 - Day 28
|
151.2 pmol/L
Standard Deviation 51.44
|
-36.6 pmol/L
Standard Deviation 98.34
|
|
Thrombogenicity Assessment - Prothrombin Fragments 1 + 2
Prothrombin Fragments 1 + 2 - Day 29
|
120.4 pmol/L
Standard Deviation 36.86
|
-67.4 pmol/L
Standard Deviation 138.05
|
|
Thrombogenicity Assessment - Prothrombin Fragments 1 + 2
Prothrombin Fragments 1 + 2 - Day 30
|
117.2 pmol/L
Standard Deviation 33.11
|
-70.6 pmol/L
Standard Deviation 118.47
|
|
Thrombogenicity Assessment - Prothrombin Fragments 1 + 2
Prothrombin Fragments 1 + 2 - Day 31
|
122.0 pmol/L
Standard Deviation 40.38
|
-65.8 pmol/L
Standard Deviation 111.81
|
|
Thrombogenicity Assessment - Prothrombin Fragments 1 + 2
Prothrombin Fragments 1 + 2 - Day 32
|
112.5 pmol/L
Standard Deviation 27.06
|
-83.5 pmol/L
Standard Deviation 148.20
|
|
Thrombogenicity Assessment - Prothrombin Fragments 1 + 2
Prothrombin Fragments 1 + 2 - Day 33
|
124.5 pmol/L
Standard Deviation 33.51
|
-71.5 pmol/L
Standard Deviation 122.25
|
|
Thrombogenicity Assessment - Prothrombin Fragments 1 + 2
Prothrombin Fragments 1 + 2 - End of Study
|
115.6 pmol/L
Standard Deviation 27.76
|
-72.2 pmol/L
Standard Deviation 143.95
|
|
Thrombogenicity Assessment - Prothrombin Fragments 1 + 2
Prothrombin Fragments 1 + 2 - Maximum change from baseline during dosing
|
—
|
-16.8 pmol/L
Standard Deviation 178.49
|
SECONDARY outcome
Timeframe: Screening, Day 1 (IV Pre-dose, SC Dose), Day 2, 3, 7, 14, 21, 28, 29, 30, 31, 32, 33, and End of Study. End of Study is the average of each subject's last recorded assessment (between Days 29 to 33).Population: Pharmacodynamic Population
Evaluation of the levels of thrombogenicity markers of a subcutaneous regimen of CB2679d
Outcome measures
| Measure |
Overall Subjects
n=5 Participants
All subjects in the PK population
|
Change From Baseline (%)
n=5 Participants
Change from Baseline in values of FIX activity levels during study
|
|---|---|---|
|
Thrombogenicity Assessment - Thrombin/Antithrombin
Thrombin/Antithrombin - End of Study
|
3.62 ug/L
Standard Deviation 1.547
|
1.34 ug/L
Standard Deviation 2.726
|
|
Thrombogenicity Assessment - Thrombin/Antithrombin
Thrombin/Antithrombin - Screening
|
9.34 ug/L
Standard Deviation 13.518
|
—
|
|
Thrombogenicity Assessment - Thrombin/Antithrombin
Thrombin/Antithrombin - Day 1, IV Pre-dose
|
1.93 ug/L
Standard Deviation 1.130
|
—
|
|
Thrombogenicity Assessment - Thrombin/Antithrombin
Thrombin/Antithrombin - Day 1, SC Dose
|
4.42 ug/L
Standard Deviation 2.724
|
2.14 ug/L
Standard Deviation 1.692
|
|
Thrombogenicity Assessment - Thrombin/Antithrombin
Thrombin/Antithrombin - Day 2
|
3.86 ug/L
Standard Deviation 1.053
|
1.58 ug/L
Standard Deviation 1.134
|
|
Thrombogenicity Assessment - Thrombin/Antithrombin
Thrombin/Antithrombin - Day 3
|
3.86 ug/L
Standard Deviation 0.808
|
1.58 ug/L
Standard Deviation 0.993
|
|
Thrombogenicity Assessment - Thrombin/Antithrombin
Thrombin/Antithrombin - Day 7
|
5.08 ug/L
Standard Deviation 2.745
|
2.80 ug/L
Standard Deviation 2.677
|
|
Thrombogenicity Assessment - Thrombin/Antithrombin
Thrombin/Antithrombin - Day 14
|
6.72 ug/L
Standard Deviation 4.017
|
4.44 ug/L
Standard Deviation 3.686
|
|
Thrombogenicity Assessment - Thrombin/Antithrombin
Thrombin/Antithrombin - Day 21
|
4.08 ug/L
Standard Deviation 1.279
|
1.80 ug/L
Standard Deviation 1.873
|
|
Thrombogenicity Assessment - Thrombin/Antithrombin
Thrombin/Antithrombin - Day 28
|
6.38 ug/L
Standard Deviation 4.581
|
4.10 ug/L
Standard Deviation 3.707
|
|
Thrombogenicity Assessment - Thrombin/Antithrombin
Thrombin/Antithrombin - Day 29
|
3.36 ug/L
Standard Deviation 0.841
|
1.08 ug/L
Standard Deviation 1.561
|
|
Thrombogenicity Assessment - Thrombin/Antithrombin
Thrombin/Antithrombin - Day 30
|
3.24 ug/L
Standard Deviation 0.684
|
0.96 ug/L
Standard Deviation 0.733
|
|
Thrombogenicity Assessment - Thrombin/Antithrombin
Thrombin/Antithrombin - Day 31
|
8.52 ug/L
Standard Deviation 13.498
|
6.24 ug/L
Standard Deviation 12.939
|
|
Thrombogenicity Assessment - Thrombin/Antithrombin
Thrombin/Antithrombin - Day 32
|
3.88 ug/L
Standard Deviation 2.244
|
1.63 ug/L
Standard Deviation 1.941
|
|
Thrombogenicity Assessment - Thrombin/Antithrombin
Thrombin/Antithrombin - Day 33
|
4.05 ug/L
Standard Deviation 2.447
|
1.80 ug/L
Standard Deviation 2.008
|
|
Thrombogenicity Assessment - Thrombin/Antithrombin
Thrombin/Antithrombin - Maximum change from baseline during dosing
|
—
|
5.44 ug/L
Standard Deviation 2.581
|
Adverse Events
Overall Subjects
Serious events: 0 serious events
Other events: 2 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Overall Subjects
n=6 participants at risk
All subjects in the Safety Population received study treatment
|
|---|---|
|
General disorders
Injection Site Reaction
|
33.3%
2/6 • Number of events 2 • TEAEs were defined as AEs that occurred on or after the first dose of study medication or worsened after the first dose of study drug in this study but not later than the date of last dose (+30 days).
|
Additional Information
Howard Levy, Chief Medical Officer
Catalyst Biosciences
Phone: +1.650.266.6871
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place