Assessing Safety, Hospitalization and Efficacy of rNAPc2 in COVID-19 (ASPEN)
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| ClinicalTrials.gov Identifier: NCT04655586 |
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Recruitment Status :
Completed
First Posted : December 7, 2020
Results First Posted : February 21, 2023
Last Update Posted : February 21, 2023
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Sponsor:
ARCA Biopharma, Inc.
Collaborator:
Colorado Prevention Center
Information provided by (Responsible Party):
ARCA Biopharma, Inc.
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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 |
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 Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 160 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 |
| Actual Primary Completion Date : | December 6, 2021 |
| Actual Study Completion Date : | March 7, 2022 |
Resource links provided by the National Library of Medicine
| Arm | Intervention/treatment |
|---|---|
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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
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Drug: rNAPc2
two dose levels of rNAPc2
Other Names:
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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
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Drug: rNAPc2
two dose levels of rNAPc2
Other Names:
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Active Comparator: Heparin
heparin at either prophylactic or therapeutic doses per Standard of Care at Institution
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Drug: Heparin
standard of care heparin per institution (therapeutic or prophylactic regimen) |
Primary Outcome Measures :
- Proportional Change in D-dimer Level From Baseline to Day 8, or Day of Discharge if Prior to Day 8 (Phase 2b) [ Time Frame: 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 :
- Proportional Change in D-dimer Level From Baseline to 24 Hours Post-dose (Day 2) and Day 3 (Phase 2b) [ Time Frame: 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 Within Eight (8) Days of Randomization as Compared to Heparin (Phase 2b) [ Time Frame: 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.
- Number of Major or Non-major Clinically Relevant Bleeding Events With rNAPc2 vs. Heparin Through Day 30 (Phase 2b) [ Time Frame: 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 High Sensitivity C-reactive Protein Laboratory Values From Baseline Through Day 8 (Phase 2b) [ Time Frame: 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 Interleukin-6 Laboratory Values From Baseline Through Day 8 (Phase 2b) [ Time Frame: 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 Tissue Factor Laboratory Values From Baseline Through Day 8 (Phase 2b) [ Time Frame: 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) [ Time Frame: 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.
Information from the National Library of Medicine
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| Ages Eligible for Study: | 18 Years to 90 Years (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Criteria
Inclusion Criteria:
- 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
Exclusion Criteria:
- 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
Information from the National Library of Medicine
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04655586
Locations
Show 24 study locations
Sponsors and Collaborators
ARCA Biopharma, Inc.
Colorado Prevention Center
Investigators
| Principal Investigator: | Marc Bonaca, MD, MPH | CPC Clinical Research |
Study Documents (Full-Text)
Documents provided by ARCA Biopharma, Inc.:
Documents provided by ARCA Biopharma, Inc.:
Study Protocol [PDF] July 7, 2021
Statistical Analysis Plan [PDF] February 24, 2022
Informed Consent Form [PDF] July 7, 2021
| Responsible Party: | ARCA Biopharma, Inc. |
| ClinicalTrials.gov Identifier: | NCT04655586 |
| Other Study ID Numbers: |
NAPc-201/301 |
| First Posted: | December 7, 2020 Key Record Dates |
| Results First Posted: | February 21, 2023 |
| Last Update Posted: | February 21, 2023 |
| Last Verified: | October 2022 |
| 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.:
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D-dimer Thromboprophylaxis Anti-coagulant Thrombotic Events |
Coagulation Inflammation Heparin |
Additional relevant MeSH terms:
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COVID-19 Pneumonia, Viral Pneumonia Respiratory Tract Infections Infections Virus Diseases Coronavirus Infections Coronaviridae Infections Nidovirales Infections |
RNA Virus Infections Lung Diseases Respiratory Tract Diseases Heparin Protein C Anticoagulants Fibrinolytic Agents Fibrin Modulating Agents Molecular Mechanisms of Pharmacological Action |