Covid19Phase 2/3ASPENNCT04655586
Assessing Safety, Hospitalization and Efficacy of rNAPc2 in COVID-19
A Phase 2/3 study testing rNAPc2 and Heparin in people with Covid19, run by ARCA Biopharma, Inc. at 24 sites in 3 countries.
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… Read more about this study
- Who is it for?
- Ages 18 to 90 years
- Conditions the study is for
- Covid19
- What is being tested?
- rNAPc2 and Heparin
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 160 participants
- Where
- 24 sitesin 3 countries
- Study dates
- 10 Dec 2020to 7 Mar 2022
- Phase
- Phase 2/3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 90 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 9Show fewer
- 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
Trial locations and contacts
24 sites in 3 countries.
24 sites in 3 countries
United States11 sites
ARCA Investigational Site #104
Aurora, Colorado, 80045
ARCA Investigational Site #117
Denver, Colorado, 80204
ARCA Investigational Site #128
Evanston, Illinois, 60201
ARCA Investigational Site #119
Fairhope, Alabama, 36532
ARCA Investigational Site #105
Falls Church, Virginia, 22042
ARCA Investigational Site #101
Jacksonville, Florida, 32209
ARCA Investigational Site #113
New Orleans, Louisiana, 70121
ARCA Investigational Site #118
Phoenix, Arizona, 85006
ARCA Investigational Site #114
Richmond, Virginia, 23230
ARCA Investigational Site #103
Tacoma, Washington, 98405
ARCA Investigational Site #120
Tucson, Arizona, 85724
Argentina8 sites
ARCA Investigational Site #111
Buenos Aires
ARCA Investigational Site #115
CABA
ARCA Investigational Site #126
Córdoba
ARCA Investigational Site #130
Rosario, Santa Fe Province
ARCA Investigational Site #112
Rosario, Sante Fe
ARCA Investigational Site #106
San Miguel de Tucumán
ARCA Investigational Site #129
San Miguel de Tucumán
ARCA Investigational Site #127
San Nicolás de los Arroyos, Buenos Aires
Brazil5 sites
ARCA Investigational Site #124
Bragança Paulista, São Paulo
ARCA Investigational Site #125
Campo Grande, Mato Grosso do Sul
ARCA Investigational Site #123
Porto Alegre
ARCA Investigational Site #122
São José do Rio Preto, São Paulo
ARCA Investigational Site #121
São Paulo
About this study
Official title: Assessing Safety, Hospitalization and Efficacy of rNAPc2 in COVID-19 (ASPEN-COVID-19)
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.
Read the 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
- Being tested
- rNAPc2, Heparin
- Keywords
- D-dimer, Thromboprophylaxis, Anti-coagulant, Thrombotic Events, Coagulation, Inflammation, Heparin
- Medical subject headings
- COVID-19, Thrombosis, Inflammation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
rNAPc2Drug
Also called AB201, Recombinant Nematode Anticoagulant Protein c2
two dose levels of rNAPc2
HeparinDrug
standard of care heparin per institution (therapeutic or prophylactic regimen)
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: 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 Receives: Drug: rNAPc2 |
| Heparin | Active comparator | heparin at either prophylactic or therapeutic doses per Standard of Care at Institution Receives: Drug: Heparin |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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)
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.
Measured: 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)
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.
Measured: 8 days
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.
Measured: 30 days
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.
Measured: 8 days
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.
Measured: 8 days
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.
Measured: 8 days
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.
Measured: 8 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Dec 2020
- Study start10 Dec 2020
- Primary completion6 Dec 2021
- Study completion7 Mar 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Covid19Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- investigational product compared to active comparator
- Masking
- Double blind
- Who is masked
- Participant, Outcomes assessor
- Enrolment
- 160 participants (actual)
Sponsor and investigators
- Lead sponsor
- ARCA Biopharma, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Colorado Prevention Center
- Responsible party
- Sponsor
- Investigators
- Marc Bonaca, MD, MPH, Principal investigator, CPC Clinical Research
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04655586
- Sponsor's protocol ID
- NAPc-201/301
- Acronym
- ASPEN
- Status last verified
- Oct 2022
- First submitted
- 2 Dec 2020
- Last updated
- 21 Feb 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 37381988
Study at a glance
From the registry record, last updated by the sponsor on 21 Feb 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Assessing Safety, Hospitalization and Efficacy of rNAPc2 in COVID-19 (ASPEN-COVID-19)
- ClinicalTrials.gov ID
- NCT04655586
- Acronym / sponsor ID
- ASPEN / NAPc-201/301
- Conditions
- Covid19
- Keywords
- D-dimer, Thromboprophylaxis, Anti-coagulant, Thrombotic Events, Coagulation, Inflammation, Heparin
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 160 participants (actual)
- Lead sponsor
- ARCA Biopharma, Inc.Industry (pharma, biotech, devices)
- Collaborators
- Colorado Prevention Center
- Study start
- 10 Dec 2020 (actual)
- Primary completion
- 6 Dec 2021 (actual)
- Study completion
- 7 Mar 2022 (actual)
- First posted
- 7 Dec 2020 (actual)
- Results
- Posted 21 Feb 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, outcomes assessor)
- Number of arms
- 3
- Model description
- investigational product compared to active comparator
| Arm | Type | Receives |
|---|---|---|
| rNAPc2 Higher Dose | Experimental | Drug: rNAPc2loading dose of 7.5 μg/kg SC on Day 1 followed by 5 μg/kg SC on Days 3 and 5 |
| rNAPc2 Lower Dose | Experimental | Drug: rNAPc2loading dose of 5 ug/kg SC on Day 1 followed by 3 ug/kg SC on Days 3 and 5 |
| Heparin | Active comparator | Drug: Heparinheparin at either prophylactic or therapeutic doses per Standard of Care at Institution |
Who may qualify
- Ages
- 18 to 90 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 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
Key exclusion criteria (9 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| rNAPc2Also: AB201, Recombinant Nematode Anticoagulant Protein c2two dose levels of rNAPc2 | Drug | rNAPc2 Higher Dose, rNAPc2 Lower Dose |
| Heparinstandard of care heparin per institution (therapeutic or prophylactic regimen) | Drug | Heparin |
Primary outcome
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.
7 secondary outcomes
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
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
Number of Major or Non-major Clinically Relevant Bleeding Events With rNAPc2 vs. Heparin Through Day 30 (Phase 2b)
Time frame: 30 days
Change in High Sensitivity C-reactive Protein Laboratory Values From Baseline Through Day 8 (Phase 2b)
Time frame: 8 days
Change in Interleukin-6 Laboratory Values From Baseline Through Day 8 (Phase 2b)
Time frame: 8 days
Change in Tissue Factor Laboratory Values From Baseline Through Day 8 (Phase 2b)
Time frame: 8 days
Change in Antiphospholipid Antibodies Laboratory Values From Baseline Through Day 8 (Anti-Beta 2 Glycoprotein IgG) (Phase 2b)
Time frame: 8 days
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Feb 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 37381988Hess 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Marc Bonaca, MD, MPH principal investigator
CPC Clinical Research
24 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing rNAPc2 and Heparin in people with Covid19, run by ARCA Biopharma, Inc. at 24 sites in 3 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 21 Feb 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 24 sites in United States, Argentina, Brazil. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 21 Feb 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04655586, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Feb 2023.