Assessing Safety, Hospitalization and Efficacy of rNAPc2 in COVID-19 (ASPEN)

• ClinicalTrials.gov Identifier: NCT04655586
• Recruitment Status: Completed
• First Posted: December 7, 2020
• Results First Posted: February 21, 2023
• Last Update Posted: February 21, 2023
• Sponsor: ARCA Biopharma, Inc.
• Collaborator: Colorado Prevention Center
• Information provided by (Responsible Party): ARCA Biopharma, Inc.

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Covid19
• Interventions: Drug: rNAPc2; Drug: Heparin
• Enrollment: 160

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.

Arm/Group Title	rNAPc2 Lower Dose	rNAPc2 Higher Dose	Heparin
Arm/Group Description	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	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	heparin at either prophylactic or therapeutic doses per Standard of Care at Institution Heparin: standard of care heparin per institution (therapeutic or prophylactic regimen)
Period Title: Overall Study
Started	40	40	80
Completed [1]	38	34	75
Not Completed	2	6	5
Reason Not Completed
Physician Decision	1	3	4
Withdrawal by Subject	1	3	1
[1] The primary reason for participants not receiving all three doses of drug and completing the study were hospital discharges.

Baseline Characteristics

Arm/Group Title		rNAPc2 Lower Dose	rNAPc2 Higher Dose	Heparin	Total
Arm/Group Description		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	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	heparin at either prophylactic or therapeutic doses per Standard of Care at Institution Heparin: standard of care heparin per institution (therapeutic or prophylactic regimen)	Total of all reporting groups
Overall Number of Baseline Participants		40	40	80	160
Baseline Analysis Population Description		The study was designed as a sequential Phase 2B/3 trial whereby both trial phases were nested in a common protocol. When the 2B top line results dictated substantial design changes for progression to Phase 3 the study was concluded as a Phase 2 trial.
Age, Categorical; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	40 participants	40 participants	80 participants	160 participants
	<=18 years	0	0	0	0
	Between 18 and 65 years	30	30	53	113
	>=65 years	10	10	27	47
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	40 participants	40 participants	80 participants	160 participants
		53.9 (13.29)	52.8 (12.6)	57.6 (12.8)	55.5 (13)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	40 participants	40 participants	80 participants	160 participants
	Female	16 40.0%	21 52.5%	32 40.0%	69 43.1%
	Male	24 60.0%	19 47.5%	48 60.0%	91 56.9%
Race (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	40 participants	40 participants	80 participants	160 participants
	American Indian or Alaska Native	3 7.5%	0 0.0%	1 1.3%	4 2.5%
	Asian	0 0.0%	0 0.0%	0 0.0%	0 0.0%
	Native Hawaiian or Other Pacific Islander	0 0.0%	0 0.0%	1 1.3%	1 0.6%
	Black or African American	10 25.0%	8 20.0%	16 20.0%	34 21.3%
	White	27 67.5%	32 80.0%	62 77.5%	121 75.6%
	More than one race	0 0.0%	0 0.0%	0 0.0%	0 0.0%
	Unknown or Not Reported	0 0.0%	0 0.0%	0 0.0%	0 0.0%
Region of Enrollment; Measure Type: Number; Unit of measure: Participants	Number Analyzed	40 participants	40 participants	80 participants	160 participants
Argentina		1	1	2	4
United States		38	38	74	150
Brazil		1	1	4	6
WHO COVID Severity [1]; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	40 participants	40 participants	80 participants	160 participants
	Mild	26 65.0%	22 55.0%	50 62.5%	98 61.3%
	Severe	14 35.0%	18 45.0%	30 37.5%	62 38.8%
		[1] Measure Description: WHO COVID Clinical Improvement scale: severe = oxygen flow rate >=20 L/min, CPAP/BiPAP, mechanical ventilator (from Vital Signs eCRF), vasopressors (dopamine, epinephrine, norepinephrine, phenylephrine) (from Concomitant Medication eCRF). Mild if none of the criteria.
D-Dimer (ng/mL); Mean (Standard Deviation); Unit of measure: ng/mL
	Number Analyzed	40 participants	40 participants	80 participants	160 participants
		450.8 (533.8)	517.4 (588.3)	864.2 (1794.8)	680.1 (1354)
D-dimer stratification (%); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	40 participants	40 participants	80 participants	160 participants
	<= 2x Upper limit of normal	18 45.0%	20 50.0%	35 43.8%	73 45.6%
	> 2x Upper limit of normal	22 55.0%	20 50.0%	45 56.3%	87 54.4%
ACTT Scale [1]; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	40 participants	40 participants	80 participants	160 participants
	1	0 0.0%	0 0.0%	0 0.0%	0 0.0%
	2	0 0.0%	0 0.0%	2 2.5%	2 1.3%
	3	6 15.0%	5 12.5%	12 15.0%	23 14.4%
	4	10 25.0%	10 25.0%	13 16.3%	33 20.6%
	5	1 2.5%	1 2.5%	3 3.8%	5 3.1%
	6	0 0.0%	0 0.0%	0 0.0%	0 0.0%
	7	0 0.0%	0 0.0%	1 1.3%	1 0.6%
	8	0 0.0%	0 0.0%	0 0.0%	0 0.0%
	Missing	23 57.5%	24 60.0%	49 61.3%	96 60.0%
		[1] Measure Description: ACTT: adaptive COVID-19 Treatment Trial Score: ACTT scale: 1 = Death, 2 = Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation, 3 = Hospitalized, on non-invasive ventilation or high flow oxygen devices, 4 = Hospitalized, requiring supplemental oxygen, 5 = Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care , 6 = Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care, 7 = Not hospitalized, limitation on activities and/or requiring home oxygen, 8 = Not hospitalized, no limitations on activities.

Outcome Measures

1. Primary Outcome

Title	Proportional Change in D-dimer Level From Baseline to Day 8, or Day of Discharge if Prior to Day 8 (Phase 2b)
Description	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

Outcome Measure Data

Analysis Population Description

Participants included in analysis for whom paired lab results were available.

Arm/Group Title	rNAPc2 Lower Dose	rNAPc2 Higher Dose	Heparin
Arm/Group Description:	loading dose of 5 ug/kg SC on Day 1 followed by 3 ug/kg SC on Days 3 and 5 rNAPc2: two dose levels of rNAPc2	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 levels of rNAPc2	heparin at either prophylactic or therapeutic doses per Standard of Care at Institution Heparin: standard of care heparin per institution (therapeutic or prophylactic regimen)
Overall Number of Participants Analyzed	33	32	70
Mean (Standard Deviation); Unit of Measure: Percent change
	137 (422.3)	41.4 (194.6)	34.7 (133.2)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	rNAPc2 Lower Dose, rNAPc2 Higher Dose, Heparin
	Comments	All rNAPc2 doses (lower and higher) were pooled and compared to Heparin for statistical analysis presentation.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.4715
	Comments	All rNAPc2 vs. Heparin
	Method	Wilcoxon Rank Sum
	Comments	[Not Specified]

2. Secondary Outcome

Title	Proportional Change in D-dimer Level From Baseline to 24 Hours Post-dose (Day 2) and Day 3 (Phase 2b)
Description	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

Outcome Measure Data

Analysis Population Description

Participants included in analysis for whom paired lab results were available.

Arm/Group Title		rNAPc2 Lower Dose	rNAPc2 Higher Dose	Heparin
Arm/Group Description:		loading dose of 5 ug/kg SC on Day 1 followed by 3 ug/kg SC on Days 3 and 5 rNAPc2: two dose levels of rNAPc2	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 levels of rNAPc2	heparin at either prophylactic or therapeutic doses per Standard of Care at Institution Heparin: standard of care heparin per institution (therapeutic or prophylactic regimen)
Overall Number of Participants Analyzed		29	23	55
Mean (Standard Deviation); Unit of Measure: percentage change
Day 2 (24h post D1 dose)	Number Analyzed	23 participants	23 participants	42 participants
		23.9 (213.9)	-0.1 (40.3)	43.5 (317.5)
Day 3 (48h post D1 dose)	Number Analyzed	29 participants	23 participants	55 participants
		65.8 (264.5)	-2.3 (68.5)	21.5 (147.3)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	rNAPc2 Lower Dose, rNAPc2 Higher Dose, Heparin
	Comments	All rNAPc2 doses (lower and higher) were pooled and compared to Heparin for statistical analysis presentation.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.1883
	Comments	[Not Specified]
	Method	Wilcoxon Rank Sum
	Comments	[Not Specified]

3. Secondary Outcome

Title	Number of Major or Non-major Clinically Relevant Bleeding Events Within Eight (8) Days of Randomization as Compared to Heparin (Phase 2b)
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	rNAPc2 Lower Dose	rNAPc2 Higher Dose	Heparin
Arm/Group Description:	loading dose of 5 ug/kg SC on Day 1 followed by 3 ug/kg SC on Days 3 and 5 rNAPc2: two dose levels of rNAPc2	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 levels of rNAPc2	heparin at either prophylactic or therapeutic doses per Standard of Care at Institution Heparin: standard of care heparin per institution (therapeutic or prophylactic regimen)
Overall Number of Participants Analyzed	38	38	80
Measure Type: Count of Participants; Unit of Measure: Participants
ISTH Major or Non-Major Clinically Relevant	0 0.0%	0 0.0%	1 1.3%
Subjects with any ISTH if Major	1 2.6%	0 0.0%	1 1.3%
TIMI Major	0 0.0%	0 0.0%	1 1.3%
TIMI Minor	0 0.0%	0 0.0%	0 0.0%
TIMI Medical attention	0 0.0%	0 0.0%	0 0.0%
TIMI Minimal	1 2.6%	0 0.0%	0 0.0%

4. Secondary Outcome

Title	Number of Major or Non-major Clinically Relevant Bleeding Events With rNAPc2 vs. Heparin Through Day 30 (Phase 2b)
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	rNAPc2 Lower Dose	rNAPc2 Higher Dose	Heparin
Arm/Group Description:	loading dose of 5 ug/kg SC on Day 1 followed by 3 ug/kg SC on Days 3 and 5 rNAPc2: two dose levels of rNAPc2	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 levels of rNAPc2	heparin at either prophylactic or therapeutic doses per Standard of Care at Institution Heparin: standard of care heparin per institution (therapeutic or prophylactic regimen)
Overall Number of Participants Analyzed	38	38	80
Measure Type: Count of Participants; Unit of Measure: Participants
ISTH Major or Non-Major Clinically Relevant	1 2.6%	1 2.6%	1 1.3%
ISTH Major	0 0.0%	1 2.6%	1 1.3%
ISTH Non-major Clinically Relevant	1 2.6%	0 0.0%	0 0.0%
ISTH Not Clinically Relevant	2 5.3%	1 2.6%	0 0.0%
Subjects With Any ISTH if Major	3 7.9%	2 5.3%	1 1.3%
TIMI Major	0 0.0%	0 0.0%	1 1.3%
TIMI Minor	0 0.0%	1 2.6%	0 0.0%
TIMI medical attention	1 2.6%	0 0.0%	0 0.0%
TIMI Minimal	2 5.3%	1 2.6%	0 0.0%

5. Secondary Outcome

Title	Change in High Sensitivity C-reactive Protein Laboratory Values From Baseline Through Day 8 (Phase 2b)
Description	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

Outcome Measure Data

Analysis Population Description

Results analyzed from participants with available lab results.

Arm/Group Title	rNAPc2 Lower Dose	rNAPc2 Higher Dose	Heparin
Arm/Group Description:	loading dose of 5 ug/kg SC on Day 1 followed by 3 ug/kg SC on Days 3 and 5 rNAPc2: two dose levels of rNAPc2	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 levels of rNAPc2	heparin at either prophylactic or therapeutic doses per Standard of Care at Institution Heparin: standard of care heparin per institution (therapeutic or prophylactic regimen)
Overall Number of Participants Analyzed	26	25	50
Mean (Standard Deviation); Unit of Measure: percent change
	-26.1 (203.9)	270.9 (1556.8)	12.8 (226.3)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	rNAPc2 Lower Dose, rNAPc2 Higher Dose, Heparin
	Comments	All rNAPc2 doses (lower and higher) were pooled and compared to Heparin for statistical analysis presentation.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	1.0
	Comments	[Not Specified]
	Method	Wilcoxon Rank Sum
	Comments	[Not Specified]

6. Secondary Outcome

Title	Change in Interleukin-6 Laboratory Values From Baseline Through Day 8 (Phase 2b)
Description	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

Outcome Measure Data

Analysis Population Description

Results analyzed from participants with available lab results.

Arm/Group Title	rNAPc2 Lower Dose	rNAPc2 Higher Dose	Heparin
Arm/Group Description:	loading dose of 5 ug/kg SC on Day 1 followed by 3 ug/kg SC on Days 3 and 5 rNAPc2: two dose levels of rNAPc2	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 levels of rNAPc2	heparin at either prophylactic or therapeutic doses per Standard of Care at Institution Heparin: standard of care heparin per institution (therapeutic or prophylactic regimen)
Overall Number of Participants Analyzed	15	17	32
Mean (Standard Deviation); Unit of Measure: percentage change
	317.4 (821.7)	768.1 (1798.3)	8.4 (113.8)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	rNAPc2 Lower Dose, rNAPc2 Higher Dose, Heparin
	Comments	All rNAPc2 doses (lower and higher) were pooled and compared to Heparin for statistical analysis presentation.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.0254
	Comments	[Not Specified]
	Method	Wilcoxon Rank Sum
	Comments	[Not Specified]

7. Secondary Outcome

Title	Change in Tissue Factor Laboratory Values From Baseline Through Day 8 (Phase 2b)
Description	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

Outcome Measure Data

Analysis Population Description

Results analyzed from participants with available lab results.

Arm/Group Title	rNAPc2 Lower Dose	rNAPc2 Higher Dose	Heparin
Arm/Group Description:	loading dose of 5 ug/kg SC on Day 1 followed by 3 ug/kg SC on Days 3 and 5 rNAPc2: two dose levels of rNAPc2	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 levels of rNAPc2	heparin at either prophylactic or therapeutic doses per Standard of Care at Institution Heparin: standard of care heparin per institution (therapeutic or prophylactic regimen)
Overall Number of Participants Analyzed	28	26	52
Mean (Standard Deviation); Unit of Measure: percentage change
	-21.2 (56.3)	-1.8 (89.2)	23.3 (103.6)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	rNAPc2 Lower Dose, rNAPc2 Higher Dose, Heparin
	Comments	All rNAPc2 doses (lower and higher) were pooled and compared to Heparin for statistical analysis presentation.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.0535
	Comments	[Not Specified]
	Method	Wilcoxon Rank Sum
	Comments	[Not Specified]

8. Secondary Outcome

Title	Change in Antiphospholipid Antibodies Laboratory Values From Baseline Through Day 8 (Anti-Beta 2 Glycoprotein IgG) (Phase 2b)
Description	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

Outcome Measure Data

Analysis Population Description

Results analyzed from participants with available lab results.

Arm/Group Title	rNAPc2 Lower Dose	rNAPc2 Higher Dose	Heparin
Arm/Group Description:	loading dose of 5 ug/kg SC on Day 1 followed by 3 ug/kg SC on Days 3 and 5 rNAPc2: two dose levels of rNAPc2	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 levels of rNAPc2	heparin at either prophylactic or therapeutic doses per Standard of Care at Institution Heparin: standard of care heparin per institution (therapeutic or prophylactic regimen)
Overall Number of Participants Analyzed	22	17	33
Mean (Standard Deviation); Unit of Measure: percentage change
	-24.04 (51.84)	-274.3 (1562.57)	62.99 (479.75)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	rNAPc2 Lower Dose, rNAPc2 Higher Dose, Heparin
	Comments	All rNAPc2 doses (lower and higher) were pooled and compared to Heparin for statistical analysis presentation.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.8300
	Comments	[Not Specified]
	Method	Wilcoxon Rank Sum
	Comments	[Not Specified]

Adverse Events

Time Frame	All AEs were collected from the time of randomization until the participant completed Day 30 or final contact, whichever was longer. All SAEs were collected from the time of consent until the participant completed Day 30 or final contact, whichever was longer. For most participants the final visit/contact was at Day 30 (up to 40 days after screening) or later if delayed due to challenges reaching the participant or obtaining final follow-up information (up to Day 251).
Adverse Event Reporting Description	Participant counts were summarized using frequencies and percentages. A participant was counted only once per category of summarization (e.g., the participant was only counted once in the overall 'Any AE' row and was counted once in each row for the specific AE category reported), and reflected the highest level of severity/relatedness reported. Data includes all participants who were randomized and received at least one dose or part of a dose of study treatment post-randomization.
Arm/Group Title	rNAPc2 Lower Dose		rNAPc2 Higher Dose		Heparin
Arm/Group Description	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		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		heparin at either prophylactic or therapeutic doses per Standard of Care at Institution Heparin: standard of care heparin per institution (therapeutic or prophylactic regimen)
All-Cause Mortality
	rNAPc2 Lower Dose		rNAPc2 Higher Dose		Heparin
	Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)
Total	5/38 (13.16%)		5/38 (13.16%)		6/80 (7.50%)
Serious Adverse Events
	rNAPc2 Lower Dose		rNAPc2 Higher Dose		Heparin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	18/38 (47.37%)		29/38 (76.32%)		26/80 (32.50%)
Blood and lymphatic system disorders
Severe coagulopathy * 2	0/38 (0.00%)	0	1/38 (2.63%)	1	0/80 (0.00%)	0
Cardiac disorders
Atrial fibriallation * 2	1/38 (2.63%)	1	0/38 (0.00%)	0	0/80 (0.00%)	0
Cardiac failure * 2	0/38 (0.00%)	0	1/38 (2.63%)	1	0/80 (0.00%)	0
Cardiac arrest * 2	0/38 (0.00%)	0	0/38 (0.00%)	0	1/80 (1.25%)	1
Ventricular tachycardia * 2	0/38 (0.00%)	0	0/38 (0.00%)	0	1/80 (1.25%)	1
Gastrointestinal disorders
Gastric ulcer * 2	0/38 (0.00%)	0	0/38 (0.00%)	0	1/80 (1.25%)	1
General disorders
Medical device thrombosis * 2	1/38 (2.63%)	1	0/38 (0.00%)	0	0/80 (0.00%)	0
Lower extremity edema * 2	0/38 (0.00%)	0	1/38 (2.63%)	1	1/80 (1.25%)	1
Hepatobiliary disorders
Cholecycstitis * 2	1/38 (2.63%)	1	0/38 (0.00%)	0	0/80 (0.00%)	0
Elevated transaminase * 2	1/38 (2.63%)	1	0/38 (0.00%)	0	0/80 (0.00%)	0
Acute hepatic failure * 2	0/38 (0.00%)	0	1/38 (2.63%)	1	0/80 (0.00%)	0
Ischaemic hepatits * 2	0/38 (0.00%)	0	1/38 (2.63%)	1	0/80 (0.00%)	0
Infections and infestations
COVID-19 pneumonia * 2	4/38 (10.53%)	4	6/38 (15.79%)	6	5/80 (6.25%)	5
Septic shock * 2	2/38 (5.26%)	2	0/38 (0.00%)	0	1/80 (1.25%)	1
Urinary tract infection * 2	1/38 (2.63%)	1	0/38 (0.00%)	0	1/80 (1.25%)	1
Abscess on limb * 2	0/38 (0.00%)	0	1/38 (2.63%)	1	0/80 (0.00%)	0
Urosepsis * 2	0/38 (0.00%)	0	1/38 (2.63%)	1	0/80 (0.00%)	0
Sepsis * 2	1/38 (2.63%)	1	1/38 (2.63%)	1	1/80 (1.25%)	1
Diverticulitis * 2	0/38 (0.00%)	0	0/38 (0.00%)	0	1/80 (1.25%)	1
Investigations
Elevated troponin * 2	1/38 (2.63%)	1	0/38 (0.00%)	0	0/80 (0.00%)	0
Worsening of elevated blood glucose * 2	0/38 (0.00%)	0	1/38 (2.63%)	1	0/80 (0.00%)	0
Metabolism and nutrition disorders
Type I diabetes * 2	0/38 (0.00%)	0	1/38 (2.63%)	1	0/80 (0.00%)	0
Metabolic acidosis * 2	0/38 (0.00%)	0	1/38 (2.63%)	1	0/80 (0.00%)	0
Hypovolemia * 2	0/38 (0.00%)	0	0/38 (0.00%)	0	1/80 (1.25%)	1
Renal and urinary disorders
Chronic kidney disease * 2	1/38 (2.63%)	1	0/38 (0.00%)	0	0/80 (0.00%)	0
Acute kidney failure * 2	3/38 (7.89%)	3	2/38 (5.26%)	2	0/80 (0.00%)	0
Acute kidney injury * 2	0/38 (0.00%)	0	3/38 (7.89%)	3	2/80 (2.50%)	2
Respiratory, thoracic and mediastinal disorders
Respiratory failure * 1	0/38 (0.00%)	0	5/38 (13.16%)	5	4/80 (5.00%)	4
Pneumothorax * 2	1/38 (2.63%)	1	0/38 (0.00%)	0	3/80 (3.75%)	3
Respiratory arrest * 2	0/38 (0.00%)	0	1/38 (2.63%)	1	1/80 (1.25%)	1
Acute respiratory distress syndrome * 2	1/38 (2.63%)	1	0/38 (0.00%)	0	0/80 (0.00%)	0
Vascular disorders
Hypotension * 2	0/38 (0.00%)	0	1/38 (2.63%)	1	2/80 (2.50%)	2
1 Term from vocabulary, MeDRA 10.0; 2 Term from vocabulary, MeDRA 24.1; * Indicates events were collected by non-systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	rNAPc2 Lower Dose		rNAPc2 Higher Dose		Heparin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	18/38 (47.37%)		18/38 (47.37%)		36/80 (45.00%)
Blood and lymphatic system disorders
Blood and lymphatic system disorders * 2	2/38 (5.26%)	2	1/38 (2.63%)	1	3/80 (3.75%)	3
Cardiac disorders
Cardiac disorders * 2	1/38 (2.63%)	1	1/38 (2.63%)	1	7/80 (8.75%)	7
Gastrointestinal disorders
Gastrointestinal disorders * 2	1/38 (2.63%)	1	3/38 (7.89%)	3	4/80 (5.00%)	4
General disorders
General disorders and administrative site conditions * 2	1/38 (2.63%)	1	3/38 (7.89%)	3	3/80 (3.75%)	3
Infections and infestations
COVID-19 Pneumonia * 1	5/38 (13.16%)	5	4/38 (10.53%)	4	5/80 (6.25%)	5
Injury, poisoning and procedural complications
Transaminases increase * 2	2/38 (5.26%)	2	0/38 (0.00%)	0	0/80 (0.00%)	0
Metabolism and nutrition disorders
Metabolism and nutrition disorder * 2	2/38 (5.26%)	2	8/38 (21.05%)	8	10/80 (12.50%)	10
Renal and urinary disorders
Acute kidney injry * 2	3/38 (7.89%)	3	5/38 (13.16%)	5	2/80 (2.50%)	2
Respiratory, thoracic and mediastinal disorders
Respiratory failure * 2	1/38 (2.63%)	4	5/38 (13.16%)	5	6/80 (7.50%)	6
Vascular disorders
Vascular disorders * 2	1/38 (2.63%)	1	1/38 (2.63%)	1	5/80 (6.25%)	5
1 Term from vocabulary, MeDRA 10.0; 2 Term from vocabulary, MeDRA 24.1; * Indicates events were collected by non-systematic assessment

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

Results Point of Contact

• Name/Title: Dr. Michael Bristow
• Organization: Arca biopharma Inc.
• Phone: 720-940-2100
• EMail: Michael.Bristow@arcabio.com

• Responsible Party: ARCA Biopharma, Inc.
• ClinicalTrials.gov Identifier: NCT04655586
• Other Study ID Numbers: NAPc-201/301
• First Submitted: December 2, 2020
• First Posted: December 7, 2020
• Results First Submitted: July 14, 2022
• Results First Posted: February 21, 2023
• Last Update Posted: February 21, 2023