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

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ClinicalTrials.gov Identifier: NCT04655586
Recruitment Status : Recruiting
First Posted : December 7, 2020
Last Update Posted : October 6, 2021
Sponsor:
Collaborator:
Colorado Prevention Center
Information provided by (Responsible Party):
ARCA Biopharma, Inc.

Tracking Information
First Submitted Date  ICMJE December 2, 2020
First Posted Date  ICMJE December 7, 2020
Last Update Posted Date October 6, 2021
Actual Study Start Date  ICMJE December 10, 2020
Estimated Primary Completion Date November 30, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 14, 2021)
  • 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 ]
    central lab D-dimer results
  • Number of major or non-major clinically relevant bleeding events within eight (8) days of randomization as compared to heparin (Phase 2b and 3) [ Time Frame: 8 days ]
    clinical events as reported by site
  • Time to recovery within thirty (30) days of randomization using the ACTT ordinal scale (Phase 3) [ Time Frame: 30 days ]
    scale as assessed by investigator and clinical adjudication committee
Original Primary Outcome Measures  ICMJE
 (submitted: December 3, 2020)
  • Change in D-dimer level from Baseline to Day 8 (Phase 2b) [ Time Frame: 8 days ]
    central lab D-dimer results
  • Number of major or non-major clinically relevant bleeding events within thirty (30) days of randomization (Phase 2b) [ Time Frame: 30 days ]
    clinical events as reported by site
  • Time to recovery within thirty (30) days of randomization using the ACTT ordinal scale (Phase 3) [ Time Frame: 30 days ]
    scale as assessed by investigator and clinical adjudication committee
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: July 14, 2021)
  • Change in D-dimer level from baseline to 24 hours post-dose (Day 2) and Day 3 (Phase 2b) [ Time Frame: 3 days ]
    central lab D-dimer results
  • Number of major or non-major clinically relevant bleeding events with rNAPc2 vs. heparin through Day 30 (Phase 2b and 3) [ Time Frame: 30 days ]
    clinical events as reported by site
  • Number of bleeding events in subjects treated with higher vs. lower dose rNAPc2 through Day 30 (Phase 2b) [ Time Frame: 30 days ]
    clinical events as reported by site
  • Time to first occurrence of a composite of thrombotic events and all-cause mortality within thirty (30) days of randomization (Phase 3 only) [ Time Frame: 30 days ]
    clinical events as reported by site
  • Time to first occurrence of thrombotic events within thirty (30) days of randomization (Phase 3 only) [ Time Frame: 30 days ]
    clinical events as reported by site
  • Time to all-cause mortality within thirty (30) days of randomization (Phase 3 only) [ Time Frame: 30 days ]
    clinical events as reported by site
  • Change in Tissue Factor laboratory values in rNAPc2 treated subjects who had clinical events related to coagulation and inflammation from baseline through Day 8 (Phase 2b) [ Time Frame: 8 days ]
    central lab samples collected per protocol
  • Change in interleukin-6 laboratory values in rNAPc2 treated subjects who had clinical events related to coagulation and inflammation from baseline through Day 8 (Phase 2b) [ Time Frame: 8 days ]
    central lab samples collected per protocol
  • Change in high sensitivity C-reactive protein laboratory values in rNAPc2 treated subjects who had clinical events related to coagulation and inflammation from baseline through Day 8 (Phase 2b) [ Time Frame: 8 days ]
    central lab samples collected per protocol
Original Secondary Outcome Measures  ICMJE
 (submitted: December 3, 2020)
  • Change in D-dimer level from baseline to Day 10 (Phase 2b) [ Time Frame: 10 days ]
    central lab D-dimer results
  • Number of major or non-major clinically relevant bleeding events with rNAPc2 vs. heparin (Phase 2b and 3) [ Time Frame: 30 days ]
    clinical events as reported by site
  • Number of bleeding events in subjects treated with higher vs. lower dose rNAPc2 at Day 10 (Phase 2b) [ Time Frame: 10 days ]
    clinical events as reported by site
  • Time to first occurrence of a composite of thrombotic events and all-cause mortality within thirty (30) days of randomization (Phase 3 only) [ Time Frame: 30 days ]
    clinical events as reported by site
  • Time to first occurrence of thrombotic events within thirty (30) days of randomization (Phase 3 only) [ Time Frame: 30 days ]
    clinical events as reported by site
  • Time to all-cause mortality within thirty (30) days of randomization (Phase 3 only) [ Time Frame: 30 days ]
    clinical events as reported by site
  • Change in Tissue Factor laboratory values in rNAPc2 treated subjects who had clinical events related to coagulation and inflammation from baseline to Days 8 and 10 (Phase 2b) [ Time Frame: 10 days ]
    central lab samples collected per protocol
  • Change in interleukin-6 laboratory values in rNAPc2 treated subjects who had clinical events related to coagulation and inflammation from baseline to Days 8 and 10 (Phase 2b) [ Time Frame: 10 days ]
    central lab samples collected per protocol
  • Change in high sensitivity C-reactive protein laboratory values in rNAPc2 treated subjects who had clinical events related to coagulation and inflammation from baseline to Days 8 and 10 (Phase 2b) [ Time Frame: 10 days ]
    central lab samples collected per protocol
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Assessing Safety, Hospitalization and Efficacy of rNAPc2 in COVID-19
Official Title  ICMJE Assessing Safety, Hospitalization and Efficacy of rNAPc2 in COVID-19 (ASPEN-COVID-19)
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 Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Phase 3
Study Design  ICMJE 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
Condition  ICMJE Covid19
Intervention  ICMJE
  • Drug: rNAPc2
    two dose levels of rNAPc2
    Other Names:
    • AB201
    • Recombinant Nematode Anticoagulant Protein c2
  • Drug: Heparin
    standard of care heparin per institution (therapeutic or prophylactic regimen)
Study Arms  ICMJE
  • 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
    Intervention: Drug: rNAPc2
  • 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
    Intervention: Drug: rNAPc2
  • Active Comparator: Heparin
    heparin at either prophylactic or therapeutic doses per Standard of Care at Institution
    Intervention: Drug: Heparin
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: July 14, 2021)
160
Original Estimated Enrollment  ICMJE
 (submitted: December 3, 2020)
100
Estimated Study Completion Date  ICMJE December 31, 2021
Estimated Primary Completion Date November 30, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 90 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Jennifer Meriwether 720-940-2132 jennifer.meriwether@arcabio.com
Listed Location Countries  ICMJE Argentina,   Brazil,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04655586
Other Study ID Numbers  ICMJE NAPc-201/301
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party ARCA Biopharma, Inc.
Study Sponsor  ICMJE ARCA Biopharma, Inc.
Collaborators  ICMJE Colorado Prevention Center
Investigators  ICMJE
Principal Investigator: Marc Bonaca, MD, MPH CPC Clinical Research
PRS Account ARCA Biopharma, Inc.
Verification Date October 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP