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

• ClinicalTrials.gov Identifier: NCT04655586
• Recruitment Status: Recruiting
• First Posted: December 7, 2020
• Last Update Posted: January 6, 2021
• Sponsor: ARCA Biopharma, Inc.
• Collaborator: Colorado Prevention Center
• Information provided by (Responsible Party): ARCA Biopharma, Inc.

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Covid19	Drug: rNAPc2; Drug: Heparin	Phase 2; Phase 3

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 Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 100 participants
• 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
• Official Title: Assessing Safety, Hospitalization and Efficacy of rNAPc2 in COVID-19 (ASPEN-COVID-19)
• Actual Study Start Date: December 10, 2020
• Estimated Primary Completion Date: April 30, 2021
• Estimated Study Completion Date: May 31, 2021

Arms and Interventions

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)

Outcome Measures

Primary Outcome Measures :

1. Change in D-dimer level from Baseline to Day 8 (Phase 2b) [ Time Frame: 8 days ]
   central lab D-dimer results
2. 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
3. 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

Secondary Outcome Measures :

1. Change in D-dimer level from baseline to Day 10 (Phase 2b) [ Time Frame: 10 days ]
   central lab D-dimer results
2. 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
3. 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
4. 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
5. 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
6. Time to all-cause mortality within thirty (30) days of randomization (Phase 3 only) [ Time Frame: 30 days ]
   clinical events as reported by site
7. 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: day 8 and day 10 ]
   central lab samples collected per protocol
8. 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: day 8 and day 10 ]
   central lab samples collected per protocol
9. 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: day 8 and day 10 ]
   central lab samples collected per protocol

Eligibility Criteria

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

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 prior to 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. Any woman who suspects she may be pregnant must have a negative pregnancy test prior to randomization. Women of child-bearing potential should agree to avoid pregnancy for 3 weeks following randomization

Exclusion Criteria:

1. High bleeding risk, e.g. major surgery within prior 1 month, history of a major bleed while receiving anticoagulation, current or planned (during current hospitalization) dual anti-platelet therapy, platelet count <25,000/uL, current anticoagulation for a medical indication. e.g. atrial fibrillation. 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 72 hours 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 a clinical study or treatment with an investigational drug or device, defined as one not approved for any indication in the US, Europe or Japan, within seven (7) days of the Screening assessment or within 5 half-lives of the investigational agent, whichever is longer

Contacts and Locations

Contacts

Contact: Jennifer Meriwether; 720-940-2132; jennifer.meriwether@arcabio.com

Locations

United States, Colorado

ARCA Investigational Site #104; Recruiting

Aurora, Colorado, United States, 80045

United States, Florida

ARCA Investigational Site #101; Recruiting

Jacksonville, Florida, United States, 32209

United States, Washington

ARCA Investigational Site #103; Recruiting

Tacoma, Washington, United States, 98405

Sponsors and Collaborators

ARCA Biopharma, Inc.

Colorado Prevention Center

Investigators

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

More Information

• Responsible Party: ARCA Biopharma, Inc.
• ClinicalTrials.gov Identifier: NCT04655586
• Other Study ID Numbers: NAPc-201/301
• First Posted: December 7, 2020
• Last Update Posted: January 6, 2021
• Last Verified: January 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

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

Keywords provided by ARCA Biopharma, Inc.:

D-dimer; Thromboprophylaxis; Anti-coagulant; Thrombotic Events; Coagulation; Inflammation; Heparin

Additional relevant MeSH terms:

Heparin; Protein C; Anticoagulants; Fibrinolytic Agents; Fibrin Modulating Agents; Molecular Mechanisms of Pharmacological Action