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

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

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.

Study Overview

• Status: Completed
• Conditions: Covid19
• Intervention / Treatment: Drug: rNAPc2; Drug: Heparin

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
• Enrollment (Actual): 160
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina
    • ARCA Investigational Site #111
  • Caba, Argentina
    • ARCA Investigational Site #115
  • Cordoba, Argentina
    • ARCA Investigational Site #126
  • San Miguel De Tucumán, Argentina
    • ARCA Investigational Site #106
  • San Miguel de Tucuman, Argentina
    • ARCA Investigational Site #129
  • Buenos Aires
    • San Nicolás, Buenos Aires, Argentina
      • ARCA Investigational Site #127
  • Santa Fe
    • Rosario, Santa Fe, Argentina
      • ARCA Investigational Site #130
  • Sante Fe
    • Rosario, Sante Fe, Argentina
      • ARCA Investigational Site #112
• Brazil
  • Porto Alegre, Brazil
    • ARCA Investigational Site #123
  • São Paulo, Brazil
    • ARCA Investigational Site #121
  • Mato Grosso Do Sul
    • Campo Grande, Mato Grosso Do Sul, Brazil
      • ARCA Investigational Site #125
  • Sao Paolo
    • Braganca Paulista, Sao Paolo, Brazil
      • ARCA Investigational Site #124
    • Sao Jose do Rio Preto, Sao Paolo, Brazil
      • ARCA Investigational Site #122
• United States
  • Alabama
    • Fairhope, Alabama, United States, 36532
      • ARCA Investigational Site #119
  • Arizona
    • Phoenix, Arizona, United States, 85006
      • ARCA Investigational Site #118
    • Tucson, Arizona, United States, 85724
      • ARCA Investigational Site #120
  • Colorado
    • Aurora, Colorado, United States, 80045
      • ARCA Investigational Site #104
    • Denver, Colorado, United States, 80204
      • ARCA Investigational Site #117
  • Florida
    • Jacksonville, Florida, United States, 32209
      • ARCA Investigational Site #101
  • Illinois
    • Evanston, Illinois, United States, 60201
      • ARCA Investigational Site #128
  • Louisiana
    • New Orleans, Louisiana, United States, 70121
      • ARCA Investigational Site #113
  • Virginia
    • Falls Church, Virginia, United States, 22042
      • ARCA Investigational Site #105
    • Richmond, Virginia, United States, 23230
      • ARCA Investigational Site #114
  • Washington
    • Tacoma, Washington, United States, 98405
      • ARCA Investigational Site #103

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 90 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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	Drug: rNAPc2; two dose levels of rNAPc2; Other Names: AB201; Recombinant Nematode Anticoagulant Protein c2
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	Drug: rNAPc2; two dose levels of rNAPc2; Other Names: AB201; Recombinant Nematode Anticoagulant Protein c2
Active Comparator: Heparin; heparin at either prophylactic or therapeutic doses per Standard of Care at Institution	Drug: Heparin; standard of care heparin per institution (therapeutic or prophylactic regimen)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	8 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	2 days and 3 days
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.	8 days
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.	30 days
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.	8 days
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.	8 days
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.	8 days
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.	8 days

Collaborators and Investigators

• Sponsor: ARCA Biopharma, Inc.
• Collaborators: Colorado Prevention Center
• Investigators: Principal Investigator: Marc Bonaca, MD, MPH, CPC Clinical Research

Study record dates

Study Major Dates

• Study Start (Actual): December 10, 2020
• Primary Completion (Actual): December 6, 2021
• Study Completion (Actual): March 7, 2022

Study Registration Dates

• First Submitted: December 2, 2020
• First Submitted That Met QC Criteria: December 3, 2020
• First Posted (Actual): December 7, 2020

Study Record Updates

• Last Update Posted (Estimate): February 21, 2023
• Last Update Submitted That Met QC Criteria: January 30, 2023
• Last Verified: October 1, 2022

More Information

Terms related to this study

• Keywords: Inflammation; D-dimer; Thromboprophylaxis; Heparin; Coagulation; Thrombotic Events; Anti-coagulant
• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19; Molecular Mechanisms of Pharmacological Action; Fibrinolytic Agents; Fibrin Modulating Agents; Heparin; Anticoagulants; Protein C
• Other Study ID Numbers: NAPc-201/301

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No