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

NCT04655586 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: NAPc-201/301
• Study Type: interventional
• Target: 160
• Locations: 3 countries
• Sites: 24

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.

Conditions

Covid19

Keywords

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

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (7)

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

  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)

  8 days

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

  30 days

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

  8 days

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

  8 days

Study Arms (3)

rNAPc2 Higher Dose

EXPERIMENTAL

loading dose of 7.5 μg/kg SC on Day 1 followed by 5 μg/kg SC on Days 3 and 5

Drug: rNAPc2

rNAPc2 Lower Dose

EXPERIMENTAL

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

Drug: rNAPc2

Heparin

ACTIVE COMPARATOR

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

Drug: Heparin

Interventions

rNAPc2 DRUG

two dose levels of rNAPc2

Also known as: AB201, Recombinant Nematode Anticoagulant Protein c2

rNAPc2 Higher Dose; rNAPc2 Lower Dose

Heparin DRUG

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

Heparin

Eligibility Criteria

• Age: 18 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 18 years and ≤ 90 years at the Screening assessment
• Weight ≥ 50 kg at randomization
• Hospitalized with a diagnosis of COVID-19 and in need of inpatient medical care
• 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
• D-dimer level \> upper limit of normal at screening
• Provided electronic or written informed consent, either personally or through a legally authorized representative (LAR)
• Must agree not to participate in a concurrent interventional study involving anticoagulation or anti-platelet therapy
• 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

You may not qualify if:

• 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.
• Sustained systolic blood pressure \< 90 mmHg considered to be clinically significant
• Persistent eGFR \<20 ml/min/1.73m2
• Known severe liver disease (e.g. bilirubin \>3.5 mg/dL (60 umol/L))
• Life expectancy estimated to be \< 72 hours based on current clinical condition
• Anticipated hospital discharge or transfer within 5 days based on current clinical condition
• Known anti-phospholipid syndrome
• Unable to receive heparin, e.g. history of heparin-induced thrombocytopenia and thrombosis (HITT)
• 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

Sponsors & Collaborators

• ARCA Biopharma, Inc.: lead
• Colorado Prevention Center: collaborator

Study Sites (24)

ARCA Investigational Site #119

Fairhope, Alabama, 36532, United States

Location

ARCA Investigational Site #118

Phoenix, Arizona, 85006, United States

Location

ARCA Investigational Site #120

Tucson, Arizona, 85724, United States

Location

ARCA Investigational Site #104

Aurora, Colorado, 80045, United States

Location

ARCA Investigational Site #117

Denver, Colorado, 80204, United States

Location

ARCA Investigational Site #101

Jacksonville, Florida, 32209, United States

Location

ARCA Investigational Site #128

Evanston, Illinois, 60201, United States

Location

ARCA Investigational Site #113

New Orleans, Louisiana, 70121, United States

Location

ARCA Investigational Site #105

Falls Church, Virginia, 22042, United States

Location

ARCA Investigational Site #114

Richmond, Virginia, 23230, United States

Location

ARCA Investigational Site #103

Tacoma, Washington, 98405, United States

Location

ARCA Investigational Site #127

San Nicolás de los Arroyos, Buenos Aires, Argentina

Location

ARCA Investigational Site #130

Rosario, Santa Fe Province, Argentina

Location

ARCA Investigational Site #112

Rosario, Sante Fe, Argentina

Location

ARCA Investigational Site #111

Buenos Aires, Argentina

Location

ARCA Investigational Site #115

CABA, Argentina

Location

ARCA Investigational Site #126

Córdoba, Argentina

Location

ARCA Investigational Site #106

San Miguel de Tucumán, Argentina

Location

ARCA Investigational Site #129

San Miguel de Tucumán, Argentina

Location

ARCA Investigational Site #125

Campo Grande, Mato Grosso do Sul, Brazil

Location

ARCA Investigational Site #124

Bragança Paulista, São Paulo, Brazil

Location

ARCA Investigational Site #122

São José do Rio Preto, São Paulo, Brazil

Location

ARCA Investigational Site #123

Porto Alegre, Brazil

Location

ARCA Investigational Site #121

São Paulo, Brazil

Location

Related Publications (1)

• 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.

  PMID: 37381988 DERIVED

MeSH Terms

Conditions

COVID-19; Thrombosis; Inflammation

Interventions

anti-coagulant protein C2, Ancylostoma caninum; Heparin

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases; Embolism and Thrombosis; Vascular Diseases; Cardiovascular Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Glycosaminoglycans; Polysaccharides; Carbohydrates

Results Point of Contact

• Title: Dr. Michael Bristow
• Organization: Arca biopharma Inc.

Michael.Bristow@arcabio.com

720-940-2100

Study Officials

• Marc Bonaca, MD, MPH

  CPC Clinical Research

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Masking Details: Participant, clinical events committee members will be blind to treatment assignment. Investigator assessing outcomes will be blinded wherever possible.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: investigational product compared to active comparator

Study Record Dates

• First Submitted: December 2, 2020
• First Posted: December 7, 2020
• Study Start: December 10, 2020
• Primary Completion: December 6, 2021
• Study Completion: March 7, 2022
• Last Updated: February 21, 2023
• Results First Posted: February 21, 2023

Record last verified: 2022-10

Data Sharing

• IPD Sharing: Will not share

Locations

AR (8); US (11); BR (5)