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

Phase 2

Completed

• Conditions: Covid19
• Interventions: Drug: rNAPc2; Drug: Heparin

• Registration Number: NCT04655586
• Lead Sponsor: ARCA Biopharma, Inc.

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 Timeline

• Study First Submitted: 2020-12-02
• Study First Submitted QC: 2020-12-03
• Study First Posted: 2020-12-07
• Study Start: 2020-12-10
• Primary Completion: 2021-12-06
• Study Completion: 2022-03-07
• Results First Submitted: 2022-07-14
• Status Verified: 2022-10
• Results First Submitted QC: 2023-01-30
• Last Update Submitted: 2023-01-30
• Results First Posted: 2023-02-21
• Last Update Posted: 2023-02-21

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 160

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
rNAPc2 Higher Dose	rNAPc2	loading dose of 7.5 μg/kg SC on Day 1 followed by 5 μg/kg SC on Days 3 and 5
Heparin	Heparin	heparin at either prophylactic or therapeutic doses per Standard of Care at Institution
rNAPc2 Lower Dose	rNAPc2	loading dose of 5 ug/kg SC on Day 1 followed by 3 ug/kg SC on Days 3 and 5

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
Change in Tissue Factor Laboratory Values From Baseline Through Day 8 (Phase 2b)	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.
Number of Major or Non-major Clinically Relevant Bleeding Events Within Eight (8) Days of Randomization as Compared to Heparin (Phase 2b)	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.
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	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 With rNAPc2 vs. Heparin Through Day 30 (Phase 2b)	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 Interleukin-6 Laboratory Values From Baseline Through Day 8 (Phase 2b)	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)	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.
Change in High Sensitivity C-reactive Protein Laboratory Values From Baseline Through Day 8 (Phase 2b)	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.

Trial Locations

Locations (24)

ARCA Investigational Site #120; 🇺🇸 Tucson, Arizona, United States

ARCA Investigational Site #112; 🇦🇷 Rosario, Sante Fe, Argentina

ARCA Investigational Site #127; 🇦🇷 San Nicolás, Buenos Aires, Argentina

ARCA Investigational Site #115; 🇦🇷 Caba, Argentina

ARCA Investigational Site #129; 🇦🇷 San Miguel de Tucuman, Argentina

ARCA Investigational Site #130; 🇦🇷 Rosario, Santa Fe, Argentina

ARCA Investigational Site #111; 🇦🇷 Buenos Aires, Argentina

ARCA Investigational Site #119; 🇺🇸 Fairhope, Alabama, United States

ARCA Investigational Site #128; 🇺🇸 Evanston, Illinois, United States

ARCA Investigational Site #106; 🇦🇷 San Miguel De Tucumán, Argentina

ARCA Investigational Site #125; 🇧🇷 Campo Grande, Mato Grosso Do Sul, Brazil

ARCA Investigational Site #105; 🇺🇸 Falls Church, Virginia, United States

ARCA Investigational Site #103; 🇺🇸 Tacoma, Washington, United States

ARCA Investigational Site #101; 🇺🇸 Jacksonville, Florida, United States

ARCA Investigational Site #126; 🇦🇷 Cordoba, Argentina

ARCA Investigational Site #123; 🇧🇷 Porto Alegre, Brazil

ARCA Investigational Site #122; 🇧🇷 Sao Jose do Rio Preto, Sao Paolo, Brazil

ARCA Investigational Site #124; 🇧🇷 Braganca Paulista, Sao Paolo, Brazil

ARCA Investigational Site #121; 🇧🇷 São Paulo, Brazil

ARCA Investigational Site #104; 🇺🇸 Aurora, Colorado, United States

ARCA Investigational Site #114; 🇺🇸 Richmond, Virginia, United States

ARCA Investigational Site #118; 🇺🇸 Phoenix, Arizona, United States

ARCA Investigational Site #117; 🇺🇸 Denver, Colorado, United States

ARCA Investigational Site #113; 🇺🇸 New Orleans, Louisiana, United States