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

Covid19 Clinical Trial

— ASPEN  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04655586
• Other study ID #: NAPc-201/301
• Status: Completed
• Phase: Phase 2/Phase 3
• Start date: December 10, 2020
• Est. completion date: March 7, 2022

Study information

• Verified date: October 2022
• Source: ARCA Biopharma, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 160
• Est. completion date: March 7, 2022
• Est. primary completion date: December 6, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 90 Years

Eligibility

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

Related Conditions & MeSH terms

• COVID-19
• Covid19

Intervention

Drug:
• rNAPc2
two dose levels of rNAPc2
• Heparin
standard of care heparin per institution (therapeutic or prophylactic regimen)

Locations

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

Sponsors (2)

Lead Sponsor	Collaborator
ARCA Biopharma, Inc.	Colorado Prevention Center

Countries where clinical trial is conducted

United States,  Argentina,  Brazil, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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