Clinical trial NCT04655586: Assessing Safety, Hospitalization and Efficacy of rNAPc2 in COVID-19
Official title: Assessing Safety, Hospitalization and Efficacy of rNAPc2 in COVID-19 (ASPEN-COVID-19)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Covid19
Keywords: D-dimer
Thromboprophylaxis
Anti-coagulant
Thrombotic Events
Coagulation
Inflammation
Heparin
Lead sponsor: ARCA Biopharma, Inc.
Sponsor class: INDUSTRY
Collaborators: name: Colorado Prevention Center
First posted: 2020-12-07
Enrollment: 160
Sex: ALL
Minimum age (years): 18
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: investigational product compared to active comparator
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Proportional Change in D-dimer Level From Baseline to Day 8, or Day of Discharge if Prior to Day 8 (Phase 2b)
timeFrame: 8 days
Secondary outcomes:
measure: Proportional Change in D-dimer Level From Baseline to 24 Hours Post-dose (Day 2) and Day 3 (Phase 2b)
timeFrame: 2 days and 3 days
measure: Number of Major or Non-major Clinically Relevant Bleeding Events Within Eight (8) Days of Randomization as Compared to Heparin (Phase 2b)
timeFrame: 8 days
measure: Number of Major or Non-major Clinically Relevant Bleeding Events With rNAPc2 vs. Heparin Through Day 30 (Phase 2b)
timeFrame: 30 days
measure: Change in High Sensitivity C-reactive Protein Laboratory Values From Baseline Through Day 8 (Phase 2b)
timeFrame: 8 days
measure: Change in Interleukin-6 Laboratory Values From Baseline Through Day 8 (Phase 2b)
timeFrame: 8 days
measure: Change in Tissue Factor Laboratory Values From Baseline Through Day 8 (Phase 2b)
timeFrame: 8 days
measure: Change in Antiphospholipid Antibodies Laboratory Values From Baseline Through Day 8 (Anti-Beta 2 Glycoprotein IgG) (Phase 2b)
timeFrame: 8 days
Other outcomes:
Locations:
city: Fairhope
country: United States
facility: ARCA Investigational Site #119
state: Alabama
city: Phoenix
country: United States
facility: ARCA Investigational Site #118
state: Arizona
city: Tucson
country: United States
facility: ARCA Investigational Site #120
state: Arizona
city: Aurora
country: United States
facility: ARCA Investigational Site #104
state: Colorado
city: Denver
country: United States
facility: ARCA Investigational Site #117
state: Colorado
city: Jacksonville
country: United States
facility: ARCA Investigational Site #101
state: Florida
city: Evanston
country: United States
facility: ARCA Investigational Site #128
state: Illinois
city: New Orleans
country: United States
facility: ARCA Investigational Site #113
state: Louisiana
city: Falls Church
country: United States
facility: ARCA Investigational Site #105
state: Virginia
city: Richmond
country: United States
facility: ARCA Investigational Site #114
state: Virginia
city: Tacoma
country: United States
facility: ARCA Investigational Site #103
state: Washington
city: San Nicolás
country: Argentina
facility: ARCA Investigational Site #127
state: Buenos Aires
city: Rosario
country: Argentina
facility: ARCA Investigational Site #130
state: Santa Fe
city: Rosario
country: Argentina
facility: ARCA Investigational Site #112
state: Sante Fe
city: Buenos Aires
country: Argentina
facility: ARCA Investigational Site #111
city: Caba
country: Argentina
facility: ARCA Investigational Site #115
city: Cordoba
country: Argentina
facility: ARCA Investigational Site #126
city: San Miguel de Tucuman
country: Argentina
facility: ARCA Investigational Site #129
city: San Miguel De Tucumán
country: Argentina
facility: ARCA Investigational Site #106
city: Campo Grande
country: Brazil
facility: ARCA Investigational Site #125
state: Mato Grosso Do Sul
city: Braganca Paulista
country: Brazil
facility: ARCA Investigational Site #124
state: Sao Paolo
city: Sao Jose do Rio Preto
country: Brazil
facility: ARCA Investigational Site #122
state: Sao Paolo
city: Porto Alegre
country: Brazil
facility: ARCA Investigational Site #123
city: São Paulo
country: Brazil
facility: ARCA Investigational Site #121
Study officials:
affiliation: CPC Clinical Research
name: Marc Bonaca, MD, MPH
role: PRINCIPAL_INVESTIGATOR
References: