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.

Tracking Information

• First Submitted Date: December 2, 2020
• First Posted Date: December 7, 2020
• Results First Submitted Date: July 14, 2022
• Results First Posted Date: February 21, 2023
• Last Update Posted Date: February 21, 2023
• Actual Study Start Date: December 10, 2020
• Actual Primary Completion Date: December 6, 2021 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: September 8, 2022)

Proportional Change in D-dimer Level From Baseline to Day 8, or Day of Discharge if Prior to Day 8 (Phase 2b) [ Time Frame: 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.

Original Primary Outcome Measures (submitted: December 3, 2020)

• Change in D-dimer level from Baseline to Day 8 (Phase 2b) [ Time Frame: 8 days ]
  central lab D-dimer results
• Number of major or non-major clinically relevant bleeding events within thirty (30) days of randomization (Phase 2b) [ Time Frame: 30 days ]
  clinical events as reported by site
• Time to recovery within thirty (30) days of randomization using the ACTT ordinal scale (Phase 3) [ Time Frame: 30 days ]
  scale as assessed by investigator and clinical adjudication committee

Current Secondary Outcome Measures (submitted: September 8, 2022)

• Proportional Change in D-dimer Level From Baseline to 24 Hours Post-dose (Day 2) and Day 3 (Phase 2b) [ Time Frame: 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.
• Number of Major or Non-major Clinically Relevant Bleeding Events Within Eight (8) Days of Randomization as Compared to Heparin (Phase 2b) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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 Interleukin-6 Laboratory Values From Baseline Through Day 8 (Phase 2b) [ Time Frame: 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 Tissue Factor Laboratory Values From Baseline Through Day 8 (Phase 2b) [ Time Frame: 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) [ Time Frame: 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.

Original Secondary Outcome Measures (submitted: December 3, 2020)

• Change in D-dimer level from baseline to Day 10 (Phase 2b) [ Time Frame: 10 days ]
  central lab D-dimer results
• Number of major or non-major clinically relevant bleeding events with rNAPc2 vs. heparin (Phase 2b and 3) [ Time Frame: 30 days ]
  clinical events as reported by site
• Number of bleeding events in subjects treated with higher vs. lower dose rNAPc2 at Day 10 (Phase 2b) [ Time Frame: 10 days ]
  clinical events as reported by site
• Time to first occurrence of a composite of thrombotic events and all-cause mortality within thirty (30) days of randomization (Phase 3 only) [ Time Frame: 30 days ]
  clinical events as reported by site
• Time to first occurrence of thrombotic events within thirty (30) days of randomization (Phase 3 only) [ Time Frame: 30 days ]
  clinical events as reported by site
• Time to all-cause mortality within thirty (30) days of randomization (Phase 3 only) [ Time Frame: 30 days ]
  clinical events as reported by site
• Change in Tissue Factor laboratory values in rNAPc2 treated subjects who had clinical events related to coagulation and inflammation from baseline to Days 8 and 10 (Phase 2b) [ Time Frame: 10 days ]
  central lab samples collected per protocol
• Change in interleukin-6 laboratory values in rNAPc2 treated subjects who had clinical events related to coagulation and inflammation from baseline to Days 8 and 10 (Phase 2b) [ Time Frame: 10 days ]
  central lab samples collected per protocol
• Change in high sensitivity C-reactive protein laboratory values in rNAPc2 treated subjects who had clinical events related to coagulation and inflammation from baseline to Days 8 and 10 (Phase 2b) [ Time Frame: 10 days ]
  central lab samples collected per protocol

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Assessing Safety, Hospitalization and Efficacy of rNAPc2 in COVID-19
• Official Title: Assessing Safety, Hospitalization and Efficacy of rNAPc2 in COVID-19 (ASPEN-COVID-19)
• 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.
• Study Type: Interventional
• Study Phase: Phase 2; Phase 3

Study Design

Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:

investigational product compared to active comparator

Masking: Double (Participant, Outcomes Assessor)
Masking Description:

Participant, clinical events committee members will be blind to treatment assignment. Investigator assessing outcomes will be blinded wherever possible.

Primary Purpose: Treatment

• Condition: Covid19

Intervention

• Drug: rNAPc2
  two dose levels of rNAPc2
  Other Names:

  • AB201
  • Recombinant Nematode Anticoagulant Protein c2
• Drug: Heparin
  standard of care heparin per institution (therapeutic or prophylactic regimen)

Study Arms

• Experimental: 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
  Intervention: Drug: rNAPc2
• Experimental: rNAPc2 Lower Dose
  loading dose of 5 ug/kg SC on Day 1 followed by 3 ug/kg SC on Days 3 and 5
  Intervention: Drug: rNAPc2
• Active Comparator: Heparin
  heparin at either prophylactic or therapeutic doses per Standard of Care at Institution
  Intervention: Drug: Heparin

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: July 14, 2021): 160
• Original Estimated Enrollment (submitted: December 3, 2020): 100
• Actual Study Completion Date: March 7, 2022
• Actual Primary Completion Date: December 6, 2021 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 90 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Argentina, Brazil, United States

Administrative Information

• NCT Number: NCT04655586
• Other Study ID Numbers: NAPc-201/301
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: ARCA Biopharma, Inc.
• Original Responsible Party: Same as current
• Current Study Sponsor: ARCA Biopharma, Inc.
• Original Study Sponsor: Same as current
• Collaborators: Colorado Prevention Center

Investigators

• Principal Investigator: Marc Bonaca, MD, MPH; CPC Clinical Research

• PRS Account: ARCA Biopharma, Inc.
• Verification Date: October 2022