Hemophilia B
Conditions
Brief summary
Phase 2b, single-center, open-label study designed to evaluate the pharmacokinetics, pharmacodynamics, efficacy and safety of subcutaneous (SC) prophylaxis treatment regimens with CB2679d in 6 adult, male subjects with severe congenital hemophilia B.
Detailed description
Single-center, open-label Phase 2b study will evaluate the PK, PD, efficacy and safety parameters of SC prophylaxis treatment regimens with CB2679d in adult subjects with hemophilia B. The study will enroll and dose subcutaneously, a total of 6 adult male subjects with severe congenital hemophilia B. During the Treatment Period, the subject will receive an IV dose of 50 IU/kg followed 35 ± 5 minutes later by a SC dose of 100 IU/kg. Daily SC doses of 100 IU/kg will be administered until Day 28 (28 total SC doses). On Day 1, PK, PD, and safety assessments will be done at pre-IV dose and repeated 35 (± 5) minutes later prior to the SC dose. Subsequent PK, PD and safety assessments will be performed pre-dose on days 2, 3, 7, 14, 21 and 28. During the Washout Period, PK, PD, and safety assessments will be done on Days 29, 30, 31, 32 and 33. Daily FIX activity levels will be measured, unless FIX activity level is known to be \< 5%, as measured by local laboratory. An End of Study visit will occur 30 days (± 2 days) after the last dose of study drug.
Interventions
BIOLOGICALCoagulation Factor IX variant
Single intravenous injection of CB2679d/Dalcinonacog alfa
Sponsors
Catalyst Biosciences
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Confirmed diagnosis of severe (\<2%) congenital hemophilia B. * Male, age 18 or older. * Agreement to use highly effective birth control throughout the study. * Affirmation of informed consent with signature confirmation before any trial-related activities. * Stated willingness to comply with all study procedures and availability for the duration of the study.
Exclusion criteria
* History or a family history of FIX inhibitors. * Positive antibody to FIX detected by central laboratory at screening. * Previous participation in and subsequent treatment in a clinical trial within the previous 30 days or 3-half-lives, whichever is longer, or absence of clinical effect. * Have a coagulation disorder other than congenital hemophilia B. * Factor IX gene mutation 128G\>A. * Significant contraindication to participation.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects Who Achieved FIX Level ≥12% | Days 7, 14, 21, 28, 29 | Subjects who achieved a FIX activity level ≥12% during the treatment period in the PK Population |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetic (PK) Analysis - AUC | 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). | Summary of Pharmacokinetic Parameters - AUC Infinity Observation and AUC to Last Non-zero Concentration |
| PK Analysis - Clearance | 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). | Summary of PK Parameters - Clearance |
| PK Analysis - Maximum Concentration During SC Dosing | 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). | Summary of PK Parameters - Maximum Concentration during SC dosing |
| PK Analysis - Half-Life and Residence Time | 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). | Summary of PK Parameters - Half-Life-1(alpha), Half-Life-1(beta), and Mean Residence Time |
| PK Analysis - Volume of Distribution at Steady-State Observed | 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). | Summary of PK Parameters - Volume of Distribution at Steady-State Observed |
| FIX Activity Levels (Actual and Change From Baseline) in All Subjects | 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). | 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. |
| Occurrence of an Antibody Response | From date of first dose of CB2679d until date of first occurrence of clinical event, assessed up to treatment Day 28 | Rate of occurrence of an antibody response to CB2679d and cross-reactive with wild-type recombinant coagulation FIX |
| Thrombogenicity Assessment - Fibrinogen | 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). | Evaluation of the levels of thrombogenicity markers of a subcutaneous regimen of CB2679d |
| Thrombogenicity Assessment - D-Dimer | 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). | Evaluation of the levels of thrombogenicity markers of a subcutaneous regimen of CB2679d |
| Thrombogenicity Assessment - Prothrombin Fragments 1 + 2 | 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). | Evaluation of the levels of thrombogenicity markers of a subcutaneous regimen of CB2679d |
| Thrombogenicity Assessment - Thrombin/Antithrombin | 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). | Evaluation of the levels of thrombogenicity markers of a subcutaneous regimen of CB2679d |
| Occurrence of Clinical Thrombotic Event | From date of first dose of CB2679d until date of first occurrence of clinical event, assessed up to treatment Day 28 | Rate of occurrence of clinical thrombotic event not attributable to another cause |
Countries
South Africa
Participant flow
Pre-assignment details
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.
Participants by arm
| Arm | Count |
|---|---|
| Overall Subjects All subjects in the Safety Population received study treatment | 6 |
| Total | 6 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | One subject discontinued on Day 7 due to injection site reactions after Day 1, 2, and 3 doses | 1 |
Baseline characteristics
| Characteristic | Overall Subjects |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 6 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 6 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 5 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 1 Participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 6 |
| other Total, other adverse events | 2 / 6 |
| serious Total, serious adverse events | 0 / 6 |
Outcome results
Primary
Number of Subjects Who Achieved FIX Level ≥12%
Subjects who achieved a FIX activity level ≥12% during the treatment period in the PK Population
Time frame: Days 7, 14, 21, 28, 29
Population: PK population. One subject not included in the PK population discontinued the study on Day 7 and had an activity level \>12%
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Overall Subjects | Number of Subjects Who Achieved FIX Level ≥12% | Day 28 | 4 Participants |
| Overall Subjects | Number of Subjects Who Achieved FIX Level ≥12% | Day 29 | 5 Participants |
| Overall Subjects | Number of Subjects Who Achieved FIX Level ≥12% | Day 7 | 3 Participants |
| Overall Subjects | Number of Subjects Who Achieved FIX Level ≥12% | Day 14 | 4 Participants |
| Overall Subjects | Number of Subjects Who Achieved FIX Level ≥12% | Day 21 | 4 Participants |
Secondary
FIX Activity Levels (Actual and Change From Baseline) in All 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.
Time frame: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Overall Subjects | FIX Activity Levels (Actual and Change From Baseline) in All Subjects | Day 14 | 18.66 % (percent) activity | Standard Deviation 7.7986 |
| Overall Subjects | FIX Activity Levels (Actual and Change From Baseline) in All Subjects | Screening | 0.24 % (percent) activity | Standard Deviation 0.5367 |
| Overall Subjects | FIX Activity Levels (Actual and Change From Baseline) in All Subjects | Day 1, IV Predose | 11.54 % (percent) activity | Standard Deviation 20.3775 |
| Overall Subjects | FIX Activity Levels (Actual and Change From Baseline) in All Subjects | Day 1, SC Dose | 25.538 % (percent) activity | Standard Deviation 9.2245 |
| Overall Subjects | FIX Activity Levels (Actual and Change From Baseline) in All Subjects | Day 2 | 15.05 % (percent) activity | Standard Deviation 4.7177 |
| Overall Subjects | FIX Activity Levels (Actual and Change From Baseline) in All Subjects | Day 3 | 13.8 % (percent) activity | Standard Deviation 2.7362 |
| Overall Subjects | FIX Activity Levels (Actual and Change From Baseline) in All Subjects | Day 7 | 13.64 % (percent) activity | Standard Deviation 4.7141 |
| Overall Subjects | FIX Activity Levels (Actual and Change From Baseline) in All Subjects | Day 21 | 18.74 % (percent) activity | Standard Deviation 6.5328 |
| Overall Subjects | FIX Activity Levels (Actual and Change From Baseline) in All Subjects | Day 28 | 19.92 % (percent) activity | Standard Deviation 6.6571 |
| Overall Subjects | FIX Activity Levels (Actual and Change From Baseline) in All Subjects | Day 29 | 19.44 % (percent) activity | Standard Deviation 4.385 |
| Overall Subjects | FIX Activity Levels (Actual and Change From Baseline) in All Subjects | Day 30 | 14.92 % (percent) activity | Standard Deviation 3.4354 |
| Overall Subjects | FIX Activity Levels (Actual and Change From Baseline) in All Subjects | Day 31 | 12.06 % (percent) activity | Standard Deviation 1.8119 |
| Overall Subjects | FIX Activity Levels (Actual and Change From Baseline) in All Subjects | Day 32 | 8.763 % (percent) activity | Standard Deviation 2.7348 |
| Overall Subjects | FIX Activity Levels (Actual and Change From Baseline) in All Subjects | Day 33 | 8.288 % (percent) activity | Standard Deviation 1.7148 |
| Overall Subjects | FIX Activity Levels (Actual and Change From Baseline) in All Subjects | End of Study | 0.32 % (percent) activity | Standard Deviation 0.7155 |
| Change From Baseline (%) | FIX Activity Levels (Actual and Change From Baseline) in All Subjects | Day 28 | 19.68 % (percent) activity | Standard Deviation 6.3622 |
| Change From Baseline (%) | FIX Activity Levels (Actual and Change From Baseline) in All Subjects | Day 32 | 8.463 % (percent) activity | Standard Deviation 2.3085 |
| Change From Baseline (%) | FIX Activity Levels (Actual and Change From Baseline) in All Subjects | Day 29 | 19.2 % (percent) activity | Standard Deviation 4.1905 |
| Change From Baseline (%) | FIX Activity Levels (Actual and Change From Baseline) in All Subjects | Day 1, SC Dose | 25.238 % (percent) activity | Standard Deviation 8.7156 |
| Change From Baseline (%) | FIX Activity Levels (Actual and Change From Baseline) in All Subjects | End of Study | 0.08 % (percent) activity | Standard Deviation 0.1789 |
| Change From Baseline (%) | FIX Activity Levels (Actual and Change From Baseline) in All Subjects | Day 2 | 14.75 % (percent) activity | Standard Deviation 4.1589 |
| Change From Baseline (%) | FIX Activity Levels (Actual and Change From Baseline) in All Subjects | Day 30 | 14.68 % (percent) activity | Standard Deviation 3.2653 |
| Change From Baseline (%) | FIX Activity Levels (Actual and Change From Baseline) in All Subjects | Day 3 | 13.5 % (percent) activity | Standard Deviation 2.5153 |
| Change From Baseline (%) | FIX Activity Levels (Actual and Change From Baseline) in All Subjects | Day 33 | 7.988 % (percent) activity | Standard Deviation 1.1707 |
| Change From Baseline (%) | FIX Activity Levels (Actual and Change From Baseline) in All Subjects | Day 7 | 13.4 % (percent) activity | Standard Deviation 4.7974 |
| Change From Baseline (%) | FIX Activity Levels (Actual and Change From Baseline) in All Subjects | Day 14 | 18.42 % (percent) activity | Standard Deviation 7.5301 |
| Change From Baseline (%) | FIX Activity Levels (Actual and Change From Baseline) in All Subjects | Day 31 | 11.82 % (percent) activity | Standard Deviation 1.4721 |
| Change From Baseline (%) | FIX Activity Levels (Actual and Change From Baseline) in All Subjects | Day 21 | 18.5 % (percent) activity | Standard Deviation 6.1895 |
| Change From Baseline (%) | 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
Occurrence of an Antibody Response
Rate of occurrence of an antibody response to CB2679d and cross-reactive with wild-type recombinant coagulation FIX
Time frame: From date of first dose of CB2679d until date of first occurrence of clinical event, assessed up to treatment Day 28
Population: Safety Population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Overall Subjects | Occurrence of an Antibody Response | Confirmed Antidrug Antibody (ADA) to DalcA | 2 Participants |
| Overall Subjects | Occurrence of an Antibody Response | Neutralizing antibody to DalcA | 0 Participants |
Secondary
Occurrence of Clinical Thrombotic Event
Rate of occurrence of clinical thrombotic event not attributable to another cause
Time frame: From date of first dose of CB2679d until date of first occurrence of clinical event, assessed up to treatment Day 28
Population: Safety Population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Overall Subjects | Occurrence of Clinical Thrombotic Event | 0 Participants |
Secondary
Pharmacokinetic (PK) Analysis - AUC
Summary of Pharmacokinetic Parameters - AUC Infinity Observation and AUC to Last Non-zero Concentration
Time frame: 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
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Overall Subjects | Pharmacokinetic (PK) Analysis - AUC | AUC Infinity Observation | 126.0306 IU/dL*day | Standard Deviation 26.80093 |
| Overall Subjects | Pharmacokinetic (PK) Analysis - AUC | AUC to Last Non-zero Concentration | 75.415 IU/dL*day | Standard Deviation 17.22908 |
Secondary
PK Analysis - Clearance
Summary of PK Parameters - Clearance
Time frame: 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
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Overall Subjects | PK Analysis - Clearance | 0.8191544 dL/day/kg | Standard Deviation 0.15349536 |
Secondary
PK Analysis - Half-Life and Residence Time
Summary of PK Parameters - Half-Life-1(alpha), Half-Life-1(beta), and Mean Residence Time
Time frame: 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
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Overall Subjects | PK Analysis - Half-Life and Residence Time | Half-Life-1(alpha) | 5.32395 days | Standard Deviation 3.049964 |
| Overall Subjects | PK Analysis - Half-Life and Residence Time | Half-Life-1(beta) | 3.87172 days | Standard Deviation 1.132563 |
| Overall Subjects | PK Analysis - Half-Life and Residence Time | Mean Residence Time | 6.1572 days | Standard Deviation 1.609332 |
Secondary
PK Analysis - Maximum Concentration During SC Dosing
Summary of PK Parameters - Maximum Concentration during SC dosing
Time frame: 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
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Overall Subjects | PK Analysis - Maximum Concentration During SC Dosing | 20.74 IU/dL | Standard Deviation 5.58 |
Secondary
PK Analysis - Volume of Distribution at Steady-State Observed
Summary of PK Parameters - Volume of Distribution at Steady-State Observed
Time frame: 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
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Overall Subjects | PK Analysis - Volume of Distribution at Steady-State Observed | 5.00736 dL/kg | Standard Deviation 1.542769 |
Secondary
Thrombogenicity Assessment - D-Dimer
Evaluation of the levels of thrombogenicity markers of a subcutaneous regimen of CB2679d
Time frame: 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
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Overall Subjects | Thrombogenicity Assessment - D-Dimer | D-Dimer - Screening | 169.6 ug/L | Standard Deviation 155.63 |
| Overall Subjects | Thrombogenicity Assessment - D-Dimer | D-Dimer - Day 1, IV Pre-dose | 218.6 ug/L | Standard Deviation 153.78 |
| Overall Subjects | Thrombogenicity Assessment - D-Dimer | D-Dimer - Day 1, SC Dose | 209.6 ug/L | Standard Deviation 183.77 |
| Overall Subjects | Thrombogenicity Assessment - D-Dimer | D-Dimer - Day 2 | 654.6 ug/L | Standard Deviation 426.46 |
| Overall Subjects | Thrombogenicity Assessment - D-Dimer | D-Dimer - Day 3 | 680.6 ug/L | Standard Deviation 405.82 |
| Overall Subjects | Thrombogenicity Assessment - D-Dimer | D-Dimer - Day 7 | 761.0 ug/L | Standard Deviation 550.1 |
| Overall Subjects | Thrombogenicity Assessment - D-Dimer | D-Dimer - Day 14 | 969.4 ug/L | Standard Deviation 993.15 |
| Overall Subjects | Thrombogenicity Assessment - D-Dimer | D-Dimer - Day 21 | 772.6 ug/L | Standard Deviation 999.62 |
| Overall Subjects | Thrombogenicity Assessment - D-Dimer | D-Dimer - Day 28 | 590.8 ug/L | Standard Deviation 311.3 |
| Overall Subjects | Thrombogenicity Assessment - D-Dimer | D-Dimer - Day 29 | 675.6 ug/L | Standard Deviation 845 |
| Overall Subjects | Thrombogenicity Assessment - D-Dimer | D-Dimer - Day 30 | 313.4 ug/L | Standard Deviation 275.43 |
| Overall Subjects | Thrombogenicity Assessment - D-Dimer | D-Dimer - Day 31 | 293.8 ug/L | Standard Deviation 242.76 |
| Overall Subjects | Thrombogenicity Assessment - D-Dimer | D-Dimer - Day 32 | 364.5 ug/L | Standard Deviation 371.95 |
| Overall Subjects | Thrombogenicity Assessment - D-Dimer | D-Dimer - Day 33 | 390.5 ug/L | Standard Deviation 323.83 |
| Overall Subjects | Thrombogenicity Assessment - D-Dimer | D-Dimer - End of Study | 212.8 ug/L | Standard Deviation 177.26 |
| Change From Baseline (%) | Thrombogenicity Assessment - D-Dimer | D-Dimer - Day 28 | 372.2 ug/L | Standard Deviation 410.31 |
| Change From Baseline (%) | Thrombogenicity Assessment - D-Dimer | D-Dimer - Day 32 | 143.5 ug/L | Standard Deviation 433.31 |
| Change From Baseline (%) | Thrombogenicity Assessment - D-Dimer | D-Dimer - Day 1, SC Dose | -9.0 ug/L | Standard Deviation 58.71 |
| Change From Baseline (%) | Thrombogenicity Assessment - D-Dimer | D-Dimer - Day 29 | 457.0 ug/L | Standard Deviation 920.85 |
| Change From Baseline (%) | Thrombogenicity Assessment - D-Dimer | D-Dimer - Day 2 | 436.0 ug/L | Standard Deviation 427.86 |
| Change From Baseline (%) | Thrombogenicity Assessment - D-Dimer | D-Dimer - End of Study | -5.8 ug/L | Standard Deviation 242.12 |
| Change From Baseline (%) | Thrombogenicity Assessment - D-Dimer | D-Dimer - Day 3 | 462.0 ug/L | Standard Deviation 378 |
| Change From Baseline (%) | Thrombogenicity Assessment - D-Dimer | D-Dimer - Day 30 | 94.8 ug/L | Standard Deviation 343.02 |
| Change From Baseline (%) | Thrombogenicity Assessment - D-Dimer | D-Dimer - Day 7 | 542.4 ug/L | Standard Deviation 572.8 |
| Change From Baseline (%) | Thrombogenicity Assessment - D-Dimer | D-Dimer - Day 33 | 169.5 ug/L | Standard Deviation 404.25 |
| Change From Baseline (%) | Thrombogenicity Assessment - D-Dimer | D-Dimer - Day 14 | 750.8 ug/L | Standard Deviation 1053.87 |
| Change From Baseline (%) | Thrombogenicity Assessment - D-Dimer | D-Dimer - Day 31 | 75.2 ug/L | Standard Deviation 314.13 |
| Change From Baseline (%) | Thrombogenicity Assessment - D-Dimer | D-Dimer - Day 21 | 554.0 ug/L | Standard Deviation 1069.36 |
| Change From Baseline (%) | Thrombogenicity Assessment - D-Dimer | D-Dimer - Maximum change from baseline during dosing | 1088.0 ug/L | Standard Deviation 921.99 |
Secondary
Thrombogenicity Assessment - Fibrinogen
Evaluation of the levels of thrombogenicity markers of a subcutaneous regimen of CB2679d
Time frame: 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
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Overall Subjects | Thrombogenicity Assessment - Fibrinogen | Fibrinogen - Day 2 | 296.2 mg/dL | Standard Deviation 72.29 |
| Overall Subjects | Thrombogenicity Assessment - Fibrinogen | Fibrinogen - Screening | 300.4 mg/dL | Standard Deviation 64.77 |
| Overall Subjects | Thrombogenicity Assessment - Fibrinogen | Fibrinogen - Day 29 | 313.2 mg/dL | Standard Deviation 73.31 |
| Overall Subjects | Thrombogenicity Assessment - Fibrinogen | Fibrinogen - Day 3 | 299.2 mg/dL | Standard Deviation 65.98 |
| Overall Subjects | Thrombogenicity Assessment - Fibrinogen | Fibrinogen - Day 30 | 306.0 mg/dL | Standard Deviation 62.38 |
| Overall Subjects | Thrombogenicity Assessment - Fibrinogen | Fibrinogen - Day 1, IV Pre-dose | 305.6 mg/dL | Standard Deviation 73.53 |
| Overall Subjects | Thrombogenicity Assessment - Fibrinogen | Fibrinogen - Day 31 | 313.8 mg/dL | Standard Deviation 76.4 |
| Overall Subjects | Thrombogenicity Assessment - Fibrinogen | Fibrinogen - Day 7 | 285.8 mg/dL | Standard Deviation 52.64 |
| Overall Subjects | Thrombogenicity Assessment - Fibrinogen | Fibrinogen - Day 32 | 300.8 mg/dL | Standard Deviation 114.93 |
| Overall Subjects | Thrombogenicity Assessment - Fibrinogen | Fibrinogen - Day 33 | 342.8 mg/dL | Standard Deviation 68.75 |
| Overall Subjects | Thrombogenicity Assessment - Fibrinogen | Fibrinogen - Day 1, SC Dose | 326.4 mg/dL | Standard Deviation 79.04 |
| Overall Subjects | Thrombogenicity Assessment - Fibrinogen | Fibrinogen - End of Study | 285.2 mg/dL | Standard Deviation 30.6 |
| Overall Subjects | Thrombogenicity Assessment - Fibrinogen | Fibrinogen - Day 14 | 272.2 mg/dL | Standard Deviation 42.81 |
| Overall Subjects | Thrombogenicity Assessment - Fibrinogen | Fibrinogen - Day 28 | 314.4 mg/dL | Standard Deviation 87.21 |
| Overall Subjects | Thrombogenicity Assessment - Fibrinogen | Fibrinogen - Day 21 | 283.6 mg/dL | Standard Deviation 55.68 |
| Change From Baseline (%) | Thrombogenicity Assessment - Fibrinogen | Fibrinogen - Maximum change from baseline during dosing | -10.4 mg/dL | Standard Deviation 103.83 |
| Change From Baseline (%) | Thrombogenicity Assessment - Fibrinogen | Fibrinogen - Day 1, SC Dose | 20.8 mg/dL | Standard Deviation 12.5 |
| Change From Baseline (%) | Thrombogenicity Assessment - Fibrinogen | Fibrinogen - Day 2 | -9.4 mg/dL | Standard Deviation 18.04 |
| Change From Baseline (%) | Thrombogenicity Assessment - Fibrinogen | Fibrinogen - Day 3 | -6.4 mg/dL | Standard Deviation 33.58 |
| Change From Baseline (%) | Thrombogenicity Assessment - Fibrinogen | Fibrinogen - Day 7 | -19.8 mg/dL | Standard Deviation 71.92 |
| Change From Baseline (%) | Thrombogenicity Assessment - Fibrinogen | Fibrinogen - Day 14 | -33.4 mg/dL | Standard Deviation 87.16 |
| Change From Baseline (%) | Thrombogenicity Assessment - Fibrinogen | Fibrinogen - Day 21 | -22.0 mg/dL | Standard Deviation 78.19 |
| Change From Baseline (%) | Thrombogenicity Assessment - Fibrinogen | Fibrinogen - Day 28 | 8.8 mg/dL | Standard Deviation 149.17 |
| Change From Baseline (%) | Thrombogenicity Assessment - Fibrinogen | Fibrinogen - Day 29 | 7.6 mg/dL | Standard Deviation 141.32 |
| Change From Baseline (%) | Thrombogenicity Assessment - Fibrinogen | Fibrinogen - Day 30 | 0.4 mg/dL | Standard Deviation 127.73 |
| Change From Baseline (%) | Thrombogenicity Assessment - Fibrinogen | Fibrinogen - Day 31 | 8.2 mg/dL | Standard Deviation 138.79 |
| Change From Baseline (%) | Thrombogenicity Assessment - Fibrinogen | Fibrinogen - Day 33 | 64.8 mg/dL | Standard Deviation 87.93 |
| Change From Baseline (%) | Thrombogenicity Assessment - Fibrinogen | Fibrinogen - End of Study | -20.4 mg/dL | Standard Deviation 101.45 |
| Change From Baseline (%) | Thrombogenicity Assessment - Fibrinogen | Fibrinogen - Day 32 | 22.8 mg/dL | Standard Deviation 107.82 |
Secondary
Thrombogenicity Assessment - Prothrombin Fragments 1 + 2
Evaluation of the levels of thrombogenicity markers of a subcutaneous regimen of CB2679d
Time frame: 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
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Overall Subjects | Thrombogenicity Assessment - Prothrombin Fragments 1 + 2 | Prothrombin Fragments 1 + 2 - Screening | 151.2 pmol/L | Standard Deviation 55.63 |
| Overall Subjects | Thrombogenicity Assessment - Prothrombin Fragments 1 + 2 | Prothrombin Fragments 1 + 2 - Day 1, IV Pre-dose | 187.8 pmol/L | Standard Deviation 126.73 |
| Overall Subjects | Thrombogenicity Assessment - Prothrombin Fragments 1 + 2 | Prothrombin Fragments 1 + 2 - Day 1, SC Dose | 195.2 pmol/L | Standard Deviation 141.9 |
| Overall Subjects | Thrombogenicity Assessment - Prothrombin Fragments 1 + 2 | Prothrombin Fragments 1 + 2 - Day 2 | 171.4 pmol/L | Standard Deviation 75.79 |
| Overall Subjects | Thrombogenicity Assessment - Prothrombin Fragments 1 + 2 | Prothrombin Fragments 1 + 2 - Day 3 | 158.8 pmol/L | Standard Deviation 63.08 |
| Overall Subjects | Thrombogenicity Assessment - Prothrombin Fragments 1 + 2 | Prothrombin Fragments 1 + 2 - Day 7 | 203.2 pmol/L | Standard Deviation 110.3 |
| Overall Subjects | Thrombogenicity Assessment - Prothrombin Fragments 1 + 2 | Prothrombin Fragments 1 + 2 - Day 14 | 192.8 pmol/L | Standard Deviation 99.38 |
| Overall Subjects | Thrombogenicity Assessment - Prothrombin Fragments 1 + 2 | Prothrombin Fragments 1 + 2 - Day 21 | 126.6 pmol/L | Standard Deviation 39.63 |
| Overall Subjects | Thrombogenicity Assessment - Prothrombin Fragments 1 + 2 | Prothrombin Fragments 1 + 2 - Day 28 | 151.2 pmol/L | Standard Deviation 51.44 |
| Overall Subjects | Thrombogenicity Assessment - Prothrombin Fragments 1 + 2 | Prothrombin Fragments 1 + 2 - Day 29 | 120.4 pmol/L | Standard Deviation 36.86 |
| Overall Subjects | Thrombogenicity Assessment - Prothrombin Fragments 1 + 2 | Prothrombin Fragments 1 + 2 - Day 30 | 117.2 pmol/L | Standard Deviation 33.11 |
| Overall Subjects | Thrombogenicity Assessment - Prothrombin Fragments 1 + 2 | Prothrombin Fragments 1 + 2 - Day 31 | 122.0 pmol/L | Standard Deviation 40.38 |
| Overall Subjects | Thrombogenicity Assessment - Prothrombin Fragments 1 + 2 | Prothrombin Fragments 1 + 2 - Day 32 | 112.5 pmol/L | Standard Deviation 27.06 |
| Overall Subjects | Thrombogenicity Assessment - Prothrombin Fragments 1 + 2 | Prothrombin Fragments 1 + 2 - Day 33 | 124.5 pmol/L | Standard Deviation 33.51 |
| Overall Subjects | Thrombogenicity Assessment - Prothrombin Fragments 1 + 2 | Prothrombin Fragments 1 + 2 - End of Study | 115.6 pmol/L | Standard Deviation 27.76 |
| Change From Baseline (%) | Thrombogenicity Assessment - Prothrombin Fragments 1 + 2 | Prothrombin Fragments 1 + 2 - Day 28 | -36.6 pmol/L | Standard Deviation 98.34 |
| Change From Baseline (%) | Thrombogenicity Assessment - Prothrombin Fragments 1 + 2 | Prothrombin Fragments 1 + 2 - Day 32 | -83.5 pmol/L | Standard Deviation 148.2 |
| Change From Baseline (%) | Thrombogenicity Assessment - Prothrombin Fragments 1 + 2 | Prothrombin Fragments 1 + 2 - Day 1, SC Dose | 7.4 pmol/L | Standard Deviation 58.11 |
| Change From Baseline (%) | Thrombogenicity Assessment - Prothrombin Fragments 1 + 2 | Prothrombin Fragments 1 + 2 - Day 29 | -67.4 pmol/L | Standard Deviation 138.05 |
| Change From Baseline (%) | Thrombogenicity Assessment - Prothrombin Fragments 1 + 2 | Prothrombin Fragments 1 + 2 - Day 2 | -16.4 pmol/L | Standard Deviation 93.75 |
| Change From Baseline (%) | Thrombogenicity Assessment - Prothrombin Fragments 1 + 2 | Prothrombin Fragments 1 + 2 - End of Study | -72.2 pmol/L | Standard Deviation 143.95 |
| Change From Baseline (%) | Thrombogenicity Assessment - Prothrombin Fragments 1 + 2 | Prothrombin Fragments 1 + 2 - Day 3 | -29.0 pmol/L | Standard Deviation 88.88 |
| Change From Baseline (%) | Thrombogenicity Assessment - Prothrombin Fragments 1 + 2 | Prothrombin Fragments 1 + 2 - Day 30 | -70.6 pmol/L | Standard Deviation 118.47 |
| Change From Baseline (%) | Thrombogenicity Assessment - Prothrombin Fragments 1 + 2 | Prothrombin Fragments 1 + 2 - Day 7 | 15.4 pmol/L | Standard Deviation 129.6 |
| Change From Baseline (%) | Thrombogenicity Assessment - Prothrombin Fragments 1 + 2 | Prothrombin Fragments 1 + 2 - Day 33 | -71.5 pmol/L | Standard Deviation 122.25 |
| Change From Baseline (%) | Thrombogenicity Assessment - Prothrombin Fragments 1 + 2 | Prothrombin Fragments 1 + 2 - Day 14 | 5.0 pmol/L | Standard Deviation 130.7 |
| Change From Baseline (%) | Thrombogenicity Assessment - Prothrombin Fragments 1 + 2 | Prothrombin Fragments 1 + 2 - Day 31 | -65.8 pmol/L | Standard Deviation 111.81 |
| Change From Baseline (%) | Thrombogenicity Assessment - Prothrombin Fragments 1 + 2 | Prothrombin Fragments 1 + 2 - Day 21 | -61.2 pmol/L | Standard Deviation 127.21 |
| Change From Baseline (%) | 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
Thrombogenicity Assessment - Thrombin/Antithrombin
Evaluation of the levels of thrombogenicity markers of a subcutaneous regimen of CB2679d
Time frame: 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
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Overall Subjects | Thrombogenicity Assessment - Thrombin/Antithrombin | Thrombin/Antithrombin - Day 28 | 6.38 ug/L | Standard Deviation 4.581 |
| Overall Subjects | Thrombogenicity Assessment - Thrombin/Antithrombin | Thrombin/Antithrombin - Day 3 | 3.86 ug/L | Standard Deviation 0.808 |
| Overall Subjects | Thrombogenicity Assessment - Thrombin/Antithrombin | Thrombin/Antithrombin - Day 29 | 3.36 ug/L | Standard Deviation 0.841 |
| Overall Subjects | Thrombogenicity Assessment - Thrombin/Antithrombin | Thrombin/Antithrombin - Day 1, SC Dose | 4.42 ug/L | Standard Deviation 2.724 |
| Overall Subjects | Thrombogenicity Assessment - Thrombin/Antithrombin | Thrombin/Antithrombin - Day 30 | 3.24 ug/L | Standard Deviation 0.684 |
| Overall Subjects | Thrombogenicity Assessment - Thrombin/Antithrombin | Thrombin/Antithrombin - Day 7 | 5.08 ug/L | Standard Deviation 2.745 |
| Overall Subjects | Thrombogenicity Assessment - Thrombin/Antithrombin | Thrombin/Antithrombin - Screening | 9.34 ug/L | Standard Deviation 13.518 |
| Overall Subjects | Thrombogenicity Assessment - Thrombin/Antithrombin | Thrombin/Antithrombin - Day 32 | 3.88 ug/L | Standard Deviation 2.244 |
| Overall Subjects | Thrombogenicity Assessment - Thrombin/Antithrombin | Thrombin/Antithrombin - Day 14 | 6.72 ug/L | Standard Deviation 4.017 |
| Overall Subjects | Thrombogenicity Assessment - Thrombin/Antithrombin | Thrombin/Antithrombin - Day 33 | 4.05 ug/L | Standard Deviation 2.447 |
| Overall Subjects | Thrombogenicity Assessment - Thrombin/Antithrombin | Thrombin/Antithrombin - Day 2 | 3.86 ug/L | Standard Deviation 1.053 |
| Overall Subjects | Thrombogenicity Assessment - Thrombin/Antithrombin | Thrombin/Antithrombin - End of Study | 3.62 ug/L | Standard Deviation 1.547 |
| Overall Subjects | Thrombogenicity Assessment - Thrombin/Antithrombin | Thrombin/Antithrombin - Day 21 | 4.08 ug/L | Standard Deviation 1.279 |
| Overall Subjects | Thrombogenicity Assessment - Thrombin/Antithrombin | Thrombin/Antithrombin - Day 31 | 8.52 ug/L | Standard Deviation 13.498 |
| Overall Subjects | Thrombogenicity Assessment - Thrombin/Antithrombin | Thrombin/Antithrombin - Day 1, IV Pre-dose | 1.93 ug/L | Standard Deviation 1.13 |
| Change From Baseline (%) | Thrombogenicity Assessment - Thrombin/Antithrombin | Thrombin/Antithrombin - Maximum change from baseline during dosing | 5.44 ug/L | Standard Deviation 2.581 |
| Change From Baseline (%) | Thrombogenicity Assessment - Thrombin/Antithrombin | Thrombin/Antithrombin - Day 1, SC Dose | 2.14 ug/L | Standard Deviation 1.692 |
| Change From Baseline (%) | Thrombogenicity Assessment - Thrombin/Antithrombin | Thrombin/Antithrombin - Day 2 | 1.58 ug/L | Standard Deviation 1.134 |
| Change From Baseline (%) | Thrombogenicity Assessment - Thrombin/Antithrombin | Thrombin/Antithrombin - Day 3 | 1.58 ug/L | Standard Deviation 0.993 |
| Change From Baseline (%) | Thrombogenicity Assessment - Thrombin/Antithrombin | Thrombin/Antithrombin - Day 7 | 2.80 ug/L | Standard Deviation 2.677 |
| Change From Baseline (%) | Thrombogenicity Assessment - Thrombin/Antithrombin | Thrombin/Antithrombin - Day 14 | 4.44 ug/L | Standard Deviation 3.686 |
| Change From Baseline (%) | Thrombogenicity Assessment - Thrombin/Antithrombin | Thrombin/Antithrombin - Day 21 | 1.80 ug/L | Standard Deviation 1.873 |
| Change From Baseline (%) | Thrombogenicity Assessment - Thrombin/Antithrombin | Thrombin/Antithrombin - Day 28 | 4.10 ug/L | Standard Deviation 3.707 |
| Change From Baseline (%) | Thrombogenicity Assessment - Thrombin/Antithrombin | Thrombin/Antithrombin - Day 29 | 1.08 ug/L | Standard Deviation 1.561 |
| Change From Baseline (%) | Thrombogenicity Assessment - Thrombin/Antithrombin | Thrombin/Antithrombin - Day 30 | 0.96 ug/L | Standard Deviation 0.733 |
| Change From Baseline (%) | Thrombogenicity Assessment - Thrombin/Antithrombin | Thrombin/Antithrombin - Day 31 | 6.24 ug/L | Standard Deviation 12.939 |
| Change From Baseline (%) | Thrombogenicity Assessment - Thrombin/Antithrombin | Thrombin/Antithrombin - Day 32 | 1.63 ug/L | Standard Deviation 1.941 |
| Change From Baseline (%) | Thrombogenicity Assessment - Thrombin/Antithrombin | Thrombin/Antithrombin - Day 33 | 1.80 ug/L | Standard Deviation 2.008 |
| Change From Baseline (%) | Thrombogenicity Assessment - Thrombin/Antithrombin | Thrombin/Antithrombin - End of Study | 1.34 ug/L | Standard Deviation 2.726 |