Covid19
Conditions
Keywords
D-dimer, Thromboprophylaxis, Anti-coagulant, Thrombotic Events, Coagulation, Inflammation, Heparin
Brief summary
Sequential randomized, multicenter, active comparator study to evaluate the hypothesis that rNAPc2 (AB201), a novel, potent and highly selective tissue factor inhibitor with anticoagulant, anti-inflammatory and potential antiviral properties, shortens time to recovery compared to heparin in hospitalized patients with COVID-19 and elevated D-dimer levels.
Detailed description
Sequential randomized, multicenter, active comparator study to evaluate the hypothesis that rNAPc2, a novel, potent and highly selective tissue factor inhibitor with anticoagulant, anti-inflammatory and potential antiviral properties, shortens time to recovery compared to heparin in hospitalized patients with COVID-19 and elevated D-dimer levels. Study participants and Clinical Endpoint Committee (CEC) members assessing the clinical endpoints will be blinded to treatment assignment. The protocol comprises sequential Phase 2b and Phase 3 studies. Analysis of Phase 2b data could lead to study discontinuation, adjustment of eligibility criteria or sample size, and will inform the rNAPc2 dose level to be studied in Phase 3.
Interventions
DRUGrNAPc2
two dose levels of rNAPc2
DRUGHeparin
standard of care heparin per institution (therapeutic or prophylactic regimen)
Sponsors
Colorado Prevention Center
ARCA Biopharma, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Outcomes Assessor)
Masking description
Participant, clinical events committee members will be blind to treatment assignment. Investigator assessing outcomes will be blinded wherever possible.
Intervention model description
investigational product compared to active comparator
Eligibility
Sex/Gender
ALL
Age
18 Years to 90 Years
Healthy volunteers
No
Inclusion criteria
1. Age ≥ 18 years and ≤ 90 years at the Screening assessment 2. Weight ≥ 50 kg at randomization 3. Hospitalized with a diagnosis of COVID-19 and in need of inpatient medical care 4. Positive for SARS-CoV-2 on nasopharyngeal, oropharyngeal or other tissue/body fluid samples by PCR or validated other test of ongoing infection (not an antibody test for prior exposure), within seven (7) days of hospitalization or screening assessment 5. D-dimer level \> upper limit of normal at screening 6. Provided electronic or written informed consent, either personally or through a legally authorized representative (LAR) 7. Must agree not to participate in a concurrent interventional study involving anticoagulation or anti-platelet therapy 8. Female patients of reproductive or child-bearing potential must be willing to use an effective method of contraception for the duration of the study, and male patients must be willing to use an effective method of contraception to avoid partner pregnancy and abstain from sperm donation for at least 90 days after last dose
Exclusion criteria
1. High bleeding risk, e.g. major surgery within prior 1 month, history of a major bleed while receiving anticoagulation, recent hemorrhagic stroke, current or planned (during current hospitalization) dual anti-platelet therapy, platelet count \<25,000/uL, current therapeutic anticoagulation for a medical indication other than COVID-19, e.g. atrial fibrillation, known thrombosis, hereditary or acquired coagulopathy treated with therapeutic anticoagulation. Patients receiving prophylactic anticoagulation are eligible if they are willing to discontinue current anticoagulation. 2. Sustained systolic blood pressure \< 90 mmHg considered to be clinically significant 3. Persistent eGFR \<20 ml/min/1.73m2 4. Known severe liver disease (e.g. bilirubin \>3.5 mg/dL (60 umol/L)) 5. Life expectancy estimated to be \< 72 hours based on current clinical condition 6. Anticipated hospital discharge or transfer within 5 days based on current clinical condition 7. Known anti-phospholipid syndrome 8. Unable to receive heparin, e.g. history of heparin-induced thrombocytopenia and thrombosis (HITT) 9. Participation in any interventional clinical study with an investigational product within seven (7) days of the Screening assessment or within 5 half-lives of the investigational agent, whichever is longer
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Proportional Change in D-dimer Level From Baseline to Day 8, or Day of Discharge if Prior to Day 8 (Phase 2b) | 8 days | Proportional change is represented as percent change, and is defined as: 100 × (D-Dimer level at Day 8 or early discharge - D-Dimer level at baseline) / D-Dimer level at baseline. Baseline and post-baseline D-Dimer results are tested in the same laboratory, i.e. both from central laboratory, or local laboratory paired samples if the central laboratory values are not available. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Major or Non-major Clinically Relevant Bleeding Events Within Eight (8) Days of Randomization as Compared to Heparin (Phase 2b) | 8 days | Clinical events as reported by site. ISTH= International Society on Thrombosis and Haemostasis, TIMI= Thrombolysis in Myocardial Infarction. Heparin Dosing Strategy as indicated by Investigator. Where subjects have more than one bleeding event recorded, only the highest level of severity was summarized. |
| Number of Major or Non-major Clinically Relevant Bleeding Events With rNAPc2 vs. Heparin Through Day 30 (Phase 2b) | 30 days | Clinical events as reported by site. ISTH= International Society on Thrombosis and Haemostasis, TIMI= Thrombolysis in Myocardial Infarction. Heparin Dosing Strategy as indicated by Investigator. Where subjects have more than one bleeding event recorded, only the highest level of severity was summarized. |
| Change in High Sensitivity C-reactive Protein Laboratory Values From Baseline Through Day 8 (Phase 2b) | 8 days | Central lab samples collected per protocol. Proportional change is represented as percent change, and is defined as: 100 × (Biomarker level at Day 8 or early discharge - Biomarker level at baseline)/Biomarker level at baseline. |
| Proportional Change in D-dimer Level From Baseline to 24 Hours Post-dose (Day 2) and Day 3 (Phase 2b) | 2 days and 3 days | Proportional change is represented as percent change, and is defined as: 100 × (D-Dimer level at Day 2/3 or early discharge - D-Dimer level at baseline)/D-Dimer level at baseline. Baseline and post-baseline D-Dimer results are tested in the same laboratory. |
| Change in Tissue Factor Laboratory Values From Baseline Through Day 8 (Phase 2b) | 8 days | Central lab samples collected per protocol. Proportional change is represented as percent change, and is defined as: 100 × (Biomarker level at Day 8 or early discharge - Biomarker level at baseline)/Biomarker level at baseline. |
| Change in Antiphospholipid Antibodies Laboratory Values From Baseline Through Day 8 (Anti-Beta 2 Glycoprotein IgG) (Phase 2b) | 8 days | Proportional change is represented as percent change, and is defined as: 100 × (Biomarker level at Day 8 or early discharge - Biomarker level at baseline)/Biomarker level at baseline. |
| Change in Interleukin-6 Laboratory Values From Baseline Through Day 8 (Phase 2b) | 8 days | Central lab samples collected per protocol. Proportional change is represented as percent change, and is defined as: 100 × (Biomarker level at Day 8 or early discharge - Biomarker level at baseline)/Biomarker level at baseline. |
Countries
Argentina, Brazil, United States
Participant flow
Recruitment details
Eligible participants were men and women (18 to 90 years) with a confirmed COVID-19 diagnosis requiring inpatient medical care and an elevated D-dimer level at screening. Enrollment began DEC2020 with the last assessment in MAR2022. 160 participants were enrolled at 15 clinical sites in Argentina, Brazil, and the United States. Originally designed as a sequential Phase 2B/3, the Ph2B top line results dictated substantial design changes for progression to Ph3 and the study was concluded at Ph2.
Pre-assignment details
All study participants provided informed consent for study participation. Eligible participants were randomized (1:1:2) to receive treatment (i.e., rNAPc2 \[1 of 2 dose regimens\] or heparin). Randomization was centralized and stratified by local laboratory D-dimer level at screening. Study participants and endpoint assessors were blinded to treatment assignment.
Participants by arm
| Arm | Count |
|---|---|
| rNAPc2 Lower Dose loading dose of 5 ug/kg SC on Day 1 followed by 3 ug/kg SC on Days 3 and 5
rNAPc2: two dose regimens of rNAPc2 | 40 |
| rNAPc2 Higher Dose loading dose of 7.5 μg/kg SC on Day 1 followed by 5 μg/kg SC on Days 3 and 5
rNAPc2: two dose regimens of rNAPc2 | 40 |
| Heparin heparin at either prophylactic or therapeutic doses per Standard of Care at Institution
Heparin: standard of care heparin per institution (therapeutic or prophylactic regimen) | 80 |
| Total | 160 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Physician Decision | 1 | 3 | 4 |
| Overall Study | Withdrawal by Subject | 1 | 3 | 1 |
Baseline characteristics
| Characteristic | Total | Heparin | rNAPc2 Higher Dose | rNAPc2 Lower Dose |
|---|---|---|---|---|
| ACTT Scale 1 | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| ACTT Scale 2 | 2 Participants | 2 Participants | 0 Participants | 0 Participants |
| ACTT Scale 3 | 23 Participants | 12 Participants | 5 Participants | 6 Participants |
| ACTT Scale 4 | 33 Participants | 13 Participants | 10 Participants | 10 Participants |
| ACTT Scale 5 | 5 Participants | 3 Participants | 1 Participants | 1 Participants |
| ACTT Scale 6 | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| ACTT Scale 7 | 1 Participants | 1 Participants | 0 Participants | 0 Participants |
| ACTT Scale 8 | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| ACTT Scale Missing | 96 Participants | 49 Participants | 24 Participants | 23 Participants |
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 47 Participants | 27 Participants | 10 Participants | 10 Participants |
| Age, Categorical Between 18 and 65 years | 113 Participants | 53 Participants | 30 Participants | 30 Participants |
| Age, Continuous | 55.5 years STANDARD_DEVIATION 13 | 57.6 years STANDARD_DEVIATION 12.8 | 52.8 years STANDARD_DEVIATION 12.6 | 53.9 years STANDARD_DEVIATION 13.29 |
| D-Dimer (ng/mL) | 680.1 ng/mL STANDARD_DEVIATION 1354 | 864.2 ng/mL STANDARD_DEVIATION 1794.8 | 517.4 ng/mL STANDARD_DEVIATION 588.3 | 450.8 ng/mL STANDARD_DEVIATION 533.8 |
| D-dimer stratification (%) <= 2x Upper limit of normal | 73 Participants | 35 Participants | 20 Participants | 18 Participants |
| D-dimer stratification (%) > 2x Upper limit of normal | 87 Participants | 45 Participants | 20 Participants | 22 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 4 Participants | 1 Participants | 0 Participants | 3 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 34 Participants | 16 Participants | 8 Participants | 10 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants | 1 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 121 Participants | 62 Participants | 32 Participants | 27 Participants |
| Region of Enrollment Argentina | 4 participants | 2 participants | 1 participants | 1 participants |
| Region of Enrollment Brazil | 6 participants | 4 participants | 1 participants | 1 participants |
| Region of Enrollment United States | 150 participants | 74 participants | 38 participants | 38 participants |
| Sex: Female, Male Female | 69 Participants | 32 Participants | 21 Participants | 16 Participants |
| Sex: Female, Male Male | 91 Participants | 48 Participants | 19 Participants | 24 Participants |
| WHO COVID Severity Mild | 98 Participants | 50 Participants | 22 Participants | 26 Participants |
| WHO COVID Severity Severe | 62 Participants | 30 Participants | 18 Participants | 14 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 5 / 38 | 5 / 38 | 6 / 80 |
| other Total, other adverse events | 18 / 38 | 18 / 38 | 36 / 80 |
| serious Total, serious adverse events | 18 / 38 | 29 / 38 | 26 / 80 |
Outcome results
Primary
Proportional Change in D-dimer Level From Baseline to Day 8, or Day of Discharge if Prior to Day 8 (Phase 2b)
Proportional change is represented as percent change, and is defined as: 100 × (D-Dimer level at Day 8 or early discharge - D-Dimer level at baseline) / D-Dimer level at baseline. Baseline and post-baseline D-Dimer results are tested in the same laboratory, i.e. both from central laboratory, or local laboratory paired samples if the central laboratory values are not available.
Time frame: 8 days
Population: Participants included in analysis for whom paired lab results were available.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| rNAPc2 Lower Dose | Proportional Change in D-dimer Level From Baseline to Day 8, or Day of Discharge if Prior to Day 8 (Phase 2b) | 137 Percent change | Standard Deviation 422.3 |
| rNAPc2 Higher Dose | Proportional Change in D-dimer Level From Baseline to Day 8, or Day of Discharge if Prior to Day 8 (Phase 2b) | 41.4 Percent change | Standard Deviation 194.6 |
| Heparin | Proportional Change in D-dimer Level From Baseline to Day 8, or Day of Discharge if Prior to Day 8 (Phase 2b) | 34.7 Percent change | Standard Deviation 133.2 |
Comparison: All rNAPc2 doses (lower and higher) were pooled and compared to Heparin for statistical analysis presentation.p-value: 0.4715Wilcoxon Rank Sum
Secondary
Change in Antiphospholipid Antibodies Laboratory Values From Baseline Through Day 8 (Anti-Beta 2 Glycoprotein IgG) (Phase 2b)
Proportional change is represented as percent change, and is defined as: 100 × (Biomarker level at Day 8 or early discharge - Biomarker level at baseline)/Biomarker level at baseline.
Time frame: 8 days
Population: Results analyzed from participants with available lab results.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| rNAPc2 Lower Dose | Change in Antiphospholipid Antibodies Laboratory Values From Baseline Through Day 8 (Anti-Beta 2 Glycoprotein IgG) (Phase 2b) | -24.04 percentage change | Standard Deviation 51.84 |
| rNAPc2 Higher Dose | Change in Antiphospholipid Antibodies Laboratory Values From Baseline Through Day 8 (Anti-Beta 2 Glycoprotein IgG) (Phase 2b) | -274.3 percentage change | Standard Deviation 1562.57 |
| Heparin | Change in Antiphospholipid Antibodies Laboratory Values From Baseline Through Day 8 (Anti-Beta 2 Glycoprotein IgG) (Phase 2b) | 62.99 percentage change | Standard Deviation 479.75 |
Comparison: All rNAPc2 doses (lower and higher) were pooled and compared to Heparin for statistical analysis presentation.p-value: 0.83Wilcoxon Rank Sum
Secondary
Change in High Sensitivity C-reactive Protein Laboratory Values From Baseline Through Day 8 (Phase 2b)
Central lab samples collected per protocol. Proportional change is represented as percent change, and is defined as: 100 × (Biomarker level at Day 8 or early discharge - Biomarker level at baseline)/Biomarker level at baseline.
Time frame: 8 days
Population: Results analyzed from participants with available lab results.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| rNAPc2 Lower Dose | Change in High Sensitivity C-reactive Protein Laboratory Values From Baseline Through Day 8 (Phase 2b) | -26.1 percent change | Standard Deviation 203.9 |
| rNAPc2 Higher Dose | Change in High Sensitivity C-reactive Protein Laboratory Values From Baseline Through Day 8 (Phase 2b) | 270.9 percent change | Standard Deviation 1556.8 |
| Heparin | Change in High Sensitivity C-reactive Protein Laboratory Values From Baseline Through Day 8 (Phase 2b) | 12.8 percent change | Standard Deviation 226.3 |
Comparison: All rNAPc2 doses (lower and higher) were pooled and compared to Heparin for statistical analysis presentation.p-value: 1Wilcoxon Rank Sum
Secondary
Change in Interleukin-6 Laboratory Values From Baseline Through Day 8 (Phase 2b)
Central lab samples collected per protocol. Proportional change is represented as percent change, and is defined as: 100 × (Biomarker level at Day 8 or early discharge - Biomarker level at baseline)/Biomarker level at baseline.
Time frame: 8 days
Population: Results analyzed from participants with available lab results.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| rNAPc2 Lower Dose | Change in Interleukin-6 Laboratory Values From Baseline Through Day 8 (Phase 2b) | 317.4 percentage change | Standard Deviation 821.7 |
| rNAPc2 Higher Dose | Change in Interleukin-6 Laboratory Values From Baseline Through Day 8 (Phase 2b) | 768.1 percentage change | Standard Deviation 1798.3 |
| Heparin | Change in Interleukin-6 Laboratory Values From Baseline Through Day 8 (Phase 2b) | 8.4 percentage change | Standard Deviation 113.8 |
Comparison: All rNAPc2 doses (lower and higher) were pooled and compared to Heparin for statistical analysis presentation.p-value: 0.0254Wilcoxon Rank Sum
Secondary
Change in Tissue Factor Laboratory Values From Baseline Through Day 8 (Phase 2b)
Central lab samples collected per protocol. Proportional change is represented as percent change, and is defined as: 100 × (Biomarker level at Day 8 or early discharge - Biomarker level at baseline)/Biomarker level at baseline.
Time frame: 8 days
Population: Results analyzed from participants with available lab results.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| rNAPc2 Lower Dose | Change in Tissue Factor Laboratory Values From Baseline Through Day 8 (Phase 2b) | -21.2 percentage change | Standard Deviation 56.3 |
| rNAPc2 Higher Dose | Change in Tissue Factor Laboratory Values From Baseline Through Day 8 (Phase 2b) | -1.8 percentage change | Standard Deviation 89.2 |
| Heparin | Change in Tissue Factor Laboratory Values From Baseline Through Day 8 (Phase 2b) | 23.3 percentage change | Standard Deviation 103.6 |
Comparison: All rNAPc2 doses (lower and higher) were pooled and compared to Heparin for statistical analysis presentation.p-value: 0.0535Wilcoxon Rank Sum
Secondary
Number of Major or Non-major Clinically Relevant Bleeding Events Within Eight (8) Days of Randomization as Compared to Heparin (Phase 2b)
Clinical events as reported by site. ISTH= International Society on Thrombosis and Haemostasis, TIMI= Thrombolysis in Myocardial Infarction. Heparin Dosing Strategy as indicated by Investigator. Where subjects have more than one bleeding event recorded, only the highest level of severity was summarized.
Time frame: 8 days
Population: Safety population includes all participants who were randomized and received at least one dose or part of a dose of study treatment post-randomization. Participants were analyzed according to the treatment actually received.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| rNAPc2 Lower Dose | Number of Major or Non-major Clinically Relevant Bleeding Events Within Eight (8) Days of Randomization as Compared to Heparin (Phase 2b) | ISTH Major or Non-Major Clinically Relevant | 0 Participants |
| rNAPc2 Lower Dose | Number of Major or Non-major Clinically Relevant Bleeding Events Within Eight (8) Days of Randomization as Compared to Heparin (Phase 2b) | Subjects with any ISTH if Major | 1 Participants |
| rNAPc2 Lower Dose | Number of Major or Non-major Clinically Relevant Bleeding Events Within Eight (8) Days of Randomization as Compared to Heparin (Phase 2b) | TIMI Major | 0 Participants |
| rNAPc2 Lower Dose | Number of Major or Non-major Clinically Relevant Bleeding Events Within Eight (8) Days of Randomization as Compared to Heparin (Phase 2b) | TIMI Minor | 0 Participants |
| rNAPc2 Lower Dose | Number of Major or Non-major Clinically Relevant Bleeding Events Within Eight (8) Days of Randomization as Compared to Heparin (Phase 2b) | TIMI Medical attention | 0 Participants |
| rNAPc2 Lower Dose | Number of Major or Non-major Clinically Relevant Bleeding Events Within Eight (8) Days of Randomization as Compared to Heparin (Phase 2b) | TIMI Minimal | 1 Participants |
| rNAPc2 Higher Dose | Number of Major or Non-major Clinically Relevant Bleeding Events Within Eight (8) Days of Randomization as Compared to Heparin (Phase 2b) | TIMI Minimal | 0 Participants |
| rNAPc2 Higher Dose | Number of Major or Non-major Clinically Relevant Bleeding Events Within Eight (8) Days of Randomization as Compared to Heparin (Phase 2b) | ISTH Major or Non-Major Clinically Relevant | 0 Participants |
| rNAPc2 Higher Dose | Number of Major or Non-major Clinically Relevant Bleeding Events Within Eight (8) Days of Randomization as Compared to Heparin (Phase 2b) | TIMI Minor | 0 Participants |
| rNAPc2 Higher Dose | Number of Major or Non-major Clinically Relevant Bleeding Events Within Eight (8) Days of Randomization as Compared to Heparin (Phase 2b) | TIMI Medical attention | 0 Participants |
| rNAPc2 Higher Dose | Number of Major or Non-major Clinically Relevant Bleeding Events Within Eight (8) Days of Randomization as Compared to Heparin (Phase 2b) | Subjects with any ISTH if Major | 0 Participants |
| rNAPc2 Higher Dose | Number of Major or Non-major Clinically Relevant Bleeding Events Within Eight (8) Days of Randomization as Compared to Heparin (Phase 2b) | TIMI Major | 0 Participants |
| Heparin | Number of Major or Non-major Clinically Relevant Bleeding Events Within Eight (8) Days of Randomization as Compared to Heparin (Phase 2b) | Subjects with any ISTH if Major | 1 Participants |
| Heparin | Number of Major or Non-major Clinically Relevant Bleeding Events Within Eight (8) Days of Randomization as Compared to Heparin (Phase 2b) | TIMI Major | 1 Participants |
| Heparin | Number of Major or Non-major Clinically Relevant Bleeding Events Within Eight (8) Days of Randomization as Compared to Heparin (Phase 2b) | TIMI Minimal | 0 Participants |
| Heparin | Number of Major or Non-major Clinically Relevant Bleeding Events Within Eight (8) Days of Randomization as Compared to Heparin (Phase 2b) | TIMI Minor | 0 Participants |
| Heparin | Number of Major or Non-major Clinically Relevant Bleeding Events Within Eight (8) Days of Randomization as Compared to Heparin (Phase 2b) | ISTH Major or Non-Major Clinically Relevant | 1 Participants |
| Heparin | Number of Major or Non-major Clinically Relevant Bleeding Events Within Eight (8) Days of Randomization as Compared to Heparin (Phase 2b) | TIMI Medical attention | 0 Participants |
Secondary
Number of Major or Non-major Clinically Relevant Bleeding Events With rNAPc2 vs. Heparin Through Day 30 (Phase 2b)
Clinical events as reported by site. ISTH= International Society on Thrombosis and Haemostasis, TIMI= Thrombolysis in Myocardial Infarction. Heparin Dosing Strategy as indicated by Investigator. Where subjects have more than one bleeding event recorded, only the highest level of severity was summarized.
Time frame: 30 days
Population: Safety population includes all participants who were randomized and received at least one dose or part of a dose of study treatment post-randomization. Participants were analyzed according to the treatment actually received.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| rNAPc2 Lower Dose | Number of Major or Non-major Clinically Relevant Bleeding Events With rNAPc2 vs. Heparin Through Day 30 (Phase 2b) | ISTH Not Clinically Relevant | 2 Participants |
| rNAPc2 Lower Dose | Number of Major or Non-major Clinically Relevant Bleeding Events With rNAPc2 vs. Heparin Through Day 30 (Phase 2b) | TIMI Minimal | 2 Participants |
| rNAPc2 Lower Dose | Number of Major or Non-major Clinically Relevant Bleeding Events With rNAPc2 vs. Heparin Through Day 30 (Phase 2b) | TIMI Major | 0 Participants |
| rNAPc2 Lower Dose | Number of Major or Non-major Clinically Relevant Bleeding Events With rNAPc2 vs. Heparin Through Day 30 (Phase 2b) | Subjects With Any ISTH if Major | 3 Participants |
| rNAPc2 Lower Dose | Number of Major or Non-major Clinically Relevant Bleeding Events With rNAPc2 vs. Heparin Through Day 30 (Phase 2b) | ISTH Major or Non-Major Clinically Relevant | 1 Participants |
| rNAPc2 Lower Dose | Number of Major or Non-major Clinically Relevant Bleeding Events With rNAPc2 vs. Heparin Through Day 30 (Phase 2b) | TIMI medical attention | 1 Participants |
| rNAPc2 Lower Dose | Number of Major or Non-major Clinically Relevant Bleeding Events With rNAPc2 vs. Heparin Through Day 30 (Phase 2b) | ISTH Non-major Clinically Relevant | 1 Participants |
| rNAPc2 Lower Dose | Number of Major or Non-major Clinically Relevant Bleeding Events With rNAPc2 vs. Heparin Through Day 30 (Phase 2b) | ISTH Major | 0 Participants |
| rNAPc2 Lower Dose | Number of Major or Non-major Clinically Relevant Bleeding Events With rNAPc2 vs. Heparin Through Day 30 (Phase 2b) | TIMI Minor | 0 Participants |
| rNAPc2 Higher Dose | Number of Major or Non-major Clinically Relevant Bleeding Events With rNAPc2 vs. Heparin Through Day 30 (Phase 2b) | Subjects With Any ISTH if Major | 2 Participants |
| rNAPc2 Higher Dose | Number of Major or Non-major Clinically Relevant Bleeding Events With rNAPc2 vs. Heparin Through Day 30 (Phase 2b) | ISTH Major or Non-Major Clinically Relevant | 1 Participants |
| rNAPc2 Higher Dose | Number of Major or Non-major Clinically Relevant Bleeding Events With rNAPc2 vs. Heparin Through Day 30 (Phase 2b) | ISTH Major | 1 Participants |
| rNAPc2 Higher Dose | Number of Major or Non-major Clinically Relevant Bleeding Events With rNAPc2 vs. Heparin Through Day 30 (Phase 2b) | ISTH Non-major Clinically Relevant | 0 Participants |
| rNAPc2 Higher Dose | Number of Major or Non-major Clinically Relevant Bleeding Events With rNAPc2 vs. Heparin Through Day 30 (Phase 2b) | ISTH Not Clinically Relevant | 1 Participants |
| rNAPc2 Higher Dose | Number of Major or Non-major Clinically Relevant Bleeding Events With rNAPc2 vs. Heparin Through Day 30 (Phase 2b) | TIMI Major | 0 Participants |
| rNAPc2 Higher Dose | Number of Major or Non-major Clinically Relevant Bleeding Events With rNAPc2 vs. Heparin Through Day 30 (Phase 2b) | TIMI Minor | 1 Participants |
| rNAPc2 Higher Dose | Number of Major or Non-major Clinically Relevant Bleeding Events With rNAPc2 vs. Heparin Through Day 30 (Phase 2b) | TIMI medical attention | 0 Participants |
| rNAPc2 Higher Dose | Number of Major or Non-major Clinically Relevant Bleeding Events With rNAPc2 vs. Heparin Through Day 30 (Phase 2b) | TIMI Minimal | 1 Participants |
| Heparin | Number of Major or Non-major Clinically Relevant Bleeding Events With rNAPc2 vs. Heparin Through Day 30 (Phase 2b) | ISTH Non-major Clinically Relevant | 0 Participants |
| Heparin | Number of Major or Non-major Clinically Relevant Bleeding Events With rNAPc2 vs. Heparin Through Day 30 (Phase 2b) | ISTH Major or Non-Major Clinically Relevant | 1 Participants |
| Heparin | Number of Major or Non-major Clinically Relevant Bleeding Events With rNAPc2 vs. Heparin Through Day 30 (Phase 2b) | TIMI Minor | 0 Participants |
| Heparin | Number of Major or Non-major Clinically Relevant Bleeding Events With rNAPc2 vs. Heparin Through Day 30 (Phase 2b) | ISTH Major | 1 Participants |
| Heparin | Number of Major or Non-major Clinically Relevant Bleeding Events With rNAPc2 vs. Heparin Through Day 30 (Phase 2b) | TIMI Minimal | 0 Participants |
| Heparin | Number of Major or Non-major Clinically Relevant Bleeding Events With rNAPc2 vs. Heparin Through Day 30 (Phase 2b) | Subjects With Any ISTH if Major | 1 Participants |
| Heparin | Number of Major or Non-major Clinically Relevant Bleeding Events With rNAPc2 vs. Heparin Through Day 30 (Phase 2b) | ISTH Not Clinically Relevant | 0 Participants |
| Heparin | Number of Major or Non-major Clinically Relevant Bleeding Events With rNAPc2 vs. Heparin Through Day 30 (Phase 2b) | TIMI medical attention | 0 Participants |
| Heparin | Number of Major or Non-major Clinically Relevant Bleeding Events With rNAPc2 vs. Heparin Through Day 30 (Phase 2b) | TIMI Major | 1 Participants |
Secondary
Proportional Change in D-dimer Level From Baseline to 24 Hours Post-dose (Day 2) and Day 3 (Phase 2b)
Proportional change is represented as percent change, and is defined as: 100 × (D-Dimer level at Day 2/3 or early discharge - D-Dimer level at baseline)/D-Dimer level at baseline. Baseline and post-baseline D-Dimer results are tested in the same laboratory.
Time frame: 2 days and 3 days
Population: Participants included in analysis for whom paired lab results were available.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| rNAPc2 Lower Dose | Proportional Change in D-dimer Level From Baseline to 24 Hours Post-dose (Day 2) and Day 3 (Phase 2b) | Day 2 (24h post D1 dose) | 23.9 percentage change | Standard Deviation 213.9 |
| rNAPc2 Lower Dose | Proportional Change in D-dimer Level From Baseline to 24 Hours Post-dose (Day 2) and Day 3 (Phase 2b) | Day 3 (48h post D1 dose) | 65.8 percentage change | Standard Deviation 264.5 |
| rNAPc2 Higher Dose | Proportional Change in D-dimer Level From Baseline to 24 Hours Post-dose (Day 2) and Day 3 (Phase 2b) | Day 2 (24h post D1 dose) | -0.1 percentage change | Standard Deviation 40.3 |
| rNAPc2 Higher Dose | Proportional Change in D-dimer Level From Baseline to 24 Hours Post-dose (Day 2) and Day 3 (Phase 2b) | Day 3 (48h post D1 dose) | -2.3 percentage change | Standard Deviation 68.5 |
| Heparin | Proportional Change in D-dimer Level From Baseline to 24 Hours Post-dose (Day 2) and Day 3 (Phase 2b) | Day 2 (24h post D1 dose) | 43.5 percentage change | Standard Deviation 317.5 |
| Heparin | Proportional Change in D-dimer Level From Baseline to 24 Hours Post-dose (Day 2) and Day 3 (Phase 2b) | Day 3 (48h post D1 dose) | 21.5 percentage change | Standard Deviation 147.3 |
Comparison: All rNAPc2 doses (lower and higher) were pooled and compared to Heparin for statistical analysis presentation.p-value: 0.1883Wilcoxon Rank Sum