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

NCT ID: NCT04655586

Last Updated: 2023-02-21

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 160 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-12-10
• Study Completion Date: 2022-03-07

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.

Conditions

Covid19

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

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

Group Type: EXPERIMENTAL

rNAPc2

Intervention Type: DRUG

two dose levels of rNAPc2

rNAPc2 Lower Dose

loading dose of 5 ug/kg SC on Day 1 followed by 3 ug/kg SC on Days 3 and 5

Group Type: EXPERIMENTAL

rNAPc2

Intervention Type: DRUG

two dose levels of rNAPc2

Heparin

heparin at either prophylactic or therapeutic doses per Standard of Care at Institution

Group Type: ACTIVE_COMPARATOR

Heparin

Intervention Type: DRUG

standard of care heparin per institution (therapeutic or prophylactic regimen)

Interventions

rNAPc2

two dose levels of rNAPc2

Intervention Type: DRUG

Heparin

standard of care heparin per institution (therapeutic or prophylactic regimen)

Intervention Type: DRUG

Other Intervention Names

AB201; Recombinant Nematode Anticoagulant Protein c2

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 90 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Colorado Prevention Center

OTHER

Sponsor Role: collaborator

ARCA Biopharma, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Marc Bonaca, MD, MPH

Role: PRINCIPAL_INVESTIGATOR

CPC Clinical Research

Locations

ARCA Investigational Site #119

Fairhope, Alabama, United States

ARCA Investigational Site #118

Phoenix, Arizona, United States

ARCA Investigational Site #120

Tucson, Arizona, United States

ARCA Investigational Site #104

Aurora, Colorado, United States

ARCA Investigational Site #117

Denver, Colorado, United States

ARCA Investigational Site #101

Jacksonville, Florida, United States

ARCA Investigational Site #128

Evanston, Illinois, United States

ARCA Investigational Site #113

New Orleans, Louisiana, United States

ARCA Investigational Site #105

Falls Church, Virginia, United States

ARCA Investigational Site #114

Richmond, Virginia, United States

ARCA Investigational Site #103

Tacoma, Washington, United States

ARCA Investigational Site #127

San Nicolás de los Arroyos, Buenos Aires, Argentina

ARCA Investigational Site #130

Rosario, Santa Fe Province, Argentina

ARCA Investigational Site #112

Rosario, Sante Fe, Argentina

ARCA Investigational Site #111

Buenos Aires, , Argentina

ARCA Investigational Site #115

CABA, , Argentina

ARCA Investigational Site #126

Córdoba, , Argentina

ARCA Investigational Site #106

San Miguel de Tucumán, , Argentina

ARCA Investigational Site #129

San Miguel de Tucumán, , Argentina

ARCA Investigational Site #125

Campo Grande, Mato Grosso do Sul, Brazil

ARCA Investigational Site #124

Bragança Paulista, São Paulo, Brazil

ARCA Investigational Site #122

São José do Rio Preto, São Paulo, Brazil

ARCA Investigational Site #123

Porto Alegre, , Brazil

ARCA Investigational Site #121

São Paulo, , Brazil

Countries

United States; Argentina; Brazil

References

Hess CN, Hsia J, Carroll IA, Nehler MR, Ruf W, Morrow DA, Nicolau JC, Berwanger O, Szarek M, Capell WH, Johri S, Pursley MS, Gupta R, Meehan PS, Franchi F, Effron MB, Marshall D, Graybill CA, Huebler SP, Keuer T, Bristow MR, Bonaca MP. Novel Tissue Factor Inhibition for Thromboprophylaxis in COVID-19: Primary Results of the ASPEN-COVID-19 Trial. Arterioscler Thromb Vasc Biol. 2023 Aug;43(8):1572-1582. doi: 10.1161/ATVBAHA.122.318748. Epub 2023 Jun 29.

Reference Type: DERIVED

PMID: 37381988 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

NAPc-201/301

Identifier Type: -

Identifier Source: org_study_id