We're building a better ClinicalTrials.gov. Check it out and tell us what you think!
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Dociparstat for the Treatment of Severe COVID-19 in Adults at High Risk of Respiratory Failure

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04389840
Recruitment Status : Terminated (Due to improvement in the Coronavirus Disease 2019 (COVID-19) pandemic and low subject accrual.)
First Posted : May 15, 2020
Results First Posted : August 30, 2022
Last Update Posted : August 30, 2022
Sponsor:
Information provided by (Responsible Party):
Chimerix

Tracking Information
First Submitted Date  ICMJE May 13, 2020
First Posted Date  ICMJE May 15, 2020
Results First Submitted Date  ICMJE May 27, 2022
Results First Posted Date  ICMJE August 30, 2022
Last Update Posted Date August 30, 2022
Actual Study Start Date  ICMJE July 8, 2020
Actual Primary Completion Date May 20, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 27, 2022)
Number of Participants Who Are Alive and Free of Invasive Mechanical Ventilation or ECMO Through Day 28 [ Time Frame: Day 1 to Day 28 (28 days) ]
The primary efficacy endpoint was to be the proportion of participants who were alive and free of invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO) through Day 28. Data also shows proportion of participants with invasive mechanical ventilation or ECMO, all-cause mortality, or early study discontinuation (<Day 25), whichever occurred first, by Day 28.
Original Primary Outcome Measures  ICMJE
 (submitted: May 13, 2020)
Proportion of participants who are alive and free of invasive mechanical ventilation [ Time Frame: Through Day 28 ]
Alive and free of invasive mechanical ventilation
Change History
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE
 (submitted: May 13, 2020)
All-cause mortality [ Time Frame: Through Day 28 ]
Time to all-cause mortality
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Dociparstat for the Treatment of Severe COVID-19 in Adults at High Risk of Respiratory Failure
Official Title  ICMJE A Phase 2/3 Study to Evaluate the Safety and Efficacy of Dociparstat Sodium for the Treatment of Severe COVID-19 in Adults at High Risk of Respiratory Failure
Brief Summary This was a randomized, double-blind, placebo-controlled Phase 2/3 study to evaluate the safety and efficacy of dociparstat sodium in adult patients with acute lung injury (ALI) due to Coronavirus Disease 2019 (COVID-19). This study was designed to determine if dociparstat sodium could accelerate recovery and prevent progression to mechanical ventilation in patients severely affected by COVID-19.
Detailed Description This was a randomized, double-blind, placebo-controlled, Phase 2/3 trial to evaluate the safety and efficacy of dociparsat sodium in adults patients with severe COVID-19 who were at high risk of respiratory failure. Eligible subjects were with confirmed COVID-19 and required hospitalization and supplemental oxygen therapy. This study was designed to determine if dociparstat sodium could accelerate recovery and prevent progression to mechanical ventilation in patients severely affected by COVID-19.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:
The first 12 subjects were to be randomized 1:1 (dociparstat:placebo) All other subjects were to be randomized 2:1 (dociparstat:placebo)
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description:
Double-blind
Primary Purpose: Treatment
Condition  ICMJE
  • Coronavirus Disease 2019 (COVID-19)
  • Acute Lung Injury
  • Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)
Intervention  ICMJE
  • Drug: Dociparstat sodium
    Dociparstat is a glycosaminoglycan derived from porcine heparin.
    Other Names:
    • DSTAT
    • CX-01
    • 2-0,3-0 desulfated heparin
    • ODSH
  • Drug: Placebo
    0.9% Normal Saline
    Other Names:
    • Normal saline
    • Sodium chloride 0.9%
    • 0.9% Normal Saline
Study Arms  ICMJE
  • Experimental: Cohort 1 dociparstat
    Subjects received 4 mg/kg of dociparstat administered as an intravenous (IV) bolus on Day 1, followed by 0.25 mg/kg/hr dociparstat by continuous IV infusion for 24 hours daily for up to 7 days (starting on Day 1 and ending on Day 8 [168 hours]).
    Intervention: Drug: Dociparstat sodium
  • Placebo Comparator: Cohort 1 placebo
    Placebo IV bolus on Day 1, followed by Placebo by continuous IV infusion for 24 hours daily for up to 7 days (starting on Day 1 and ending on Day 8 [168 hours])
    Intervention: Drug: Placebo
  • Experimental: Cohort 2 dociparstat
    Subjects received 4 mg/kg of dociparstat administered as an intravenous (IV) bolus on Day 1, followed by 0.325 mg/kg/hr dociparstat by continuous IV infusion for 24 hours daily for up to 7 days (starting on Day 1 and ending on Day 8 [168 hours]).
    Intervention: Drug: Dociparstat sodium
  • Placebo Comparator: Cohort 2 placebo
    Subjects received placebo IV bolus on Day 1, followed by placebo by continuous IV infusion for 24 hours daily for up to 7 days (starting on Day 1 and ending on Day 8 [168 hours]).
    Intervention: Drug: Placebo
  • Experimental: Cohort 3 dociparstat
    Subjects received 4 mg/kg of dociparstat administered as an intravenous (IV) bolus on Day 1, followed by 0.325 mg/kg/hr dociparstat by continuous IV infusion for 24 hours daily for up to 7 days (starting on Day 1 and ending on Day 8 [168 hours]).
    Intervention: Drug: Dociparstat sodium
  • Placebo Comparator: Cohort 3 placebo
    Subjects received placebo IV bolus on Day 1, followed by placebo by continuous IV infusion for 24 hours daily for up to 7 days (starting on Day 1 and ending on Day 8 [168 hours]).
    Intervention: Drug: Placebo
Publications *

*   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 Terminated
Actual Enrollment  ICMJE
 (submitted: May 27, 2022)
27
Original Estimated Enrollment  ICMJE
 (submitted: May 13, 2020)
524
Actual Study Completion Date  ICMJE May 20, 2021
Actual Primary Completion Date May 20, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

A potential participant must have met all the following criteria to be included in the study:

  1. Was hospitalized for laboratory-documented Coronavirus Disease 2019 (COVID-19) (e.g., positive for severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2] via nasopharyngeal swab real time polymerase chain reaction [RT-PCR; or other commercial or public health assay]).
  2. Was aged ≥18 years and ≤85 years.
  3. Had a resting oxygen saturation (SaO2) of <94% while breathing ambient air.
  4. Had a score of 3 or 4 on the National Institute of Allergy and Infectious Diseases (NIAID) ordinal scale (required supplemental oxygen or non-invasive ventilation).
  5. Had provided informed consent to participate in the study (by participant or legally-acceptable representative).

Exclusion Criteria:

A potential participant who met any of the following criteria was not eligible to participate in the study:

  1. Was currently receiving invasive mechanical ventilation (e.g., via an endotracheal tube) (score of 2 on NIAID ordinal scale).
  2. Had severe chronic respiratory disease, defined by any oxygen requirement prior to incident COVID-19.
  3. Had active or uncontrolled bleeding at the time of randomization; a bleeding disorder, either inherited or caused by disease; history of known arterial-venous malformation, intracranial hemorrhage, or suspected or known cerebral aneurysm; or clinically significant (in the judgment of the Investigator) gastrointestinal bleeding within the 3 weeks prior to randomization.
  4. Was receiving any other investigational (non-approved) therapy for the treatment of COVID-19 or participating in the treatment period of any other therapeutic intervention clinical study. Participating in the follow-up period of an interventional study may be permitted with prior medical monitor approval; participation in an observational study is permitted.
  5. Was receiving systemic corticosteroids for a chronic condition.
  6. Was receiving chronic anticoagulation with warfarin or direct oral anticoagulants (e.g., rivaroxaban, dabigatran, apixaban, edoxaban).
  7. Was receiving or anticipated to require other systemic anticoagulation dosing at a therapeutic intensity. Prophylaxis of venous thromboembolism (VTE) using subcutaneous (SC) unfractionated heparin or enoxaparin was permitted with appropriate monitoring of coagulation status and within the guidelines described in the protocol.
  8. Was receiving antiplatelet therapy, alone or in combination, including aspirin and other antiplatelet agents (e.g., clopidogrel, ticagrelor, and prasugrel), unless able to discontinue these agents at the time of randomization and was able to remain off these agents throughout the duration of the study intervention infusion period.
  9. Had treatment with systemic (non-steroid) immunomodulators or immunosuppressant medications, including but not limited to tumor necrosis factor (TNF) inhibitors, anti-interleukin-1 agents and Janus kinase (JAK) inhibitors within 5 half-lives or 30 days (whichever was longer) prior to randomization.
  10. Had a history of congestive heart failure requiring hospitalization.
  11. Had active pericarditis (based on clinical assessment).
  12. Had malignancy or other irreversible disease or condition for which 6-month mortality was estimated ≥50%.
  13. Had a corrected QT interval (QTc) >500 msec (or >530-550 msec in participants with QRS greater than >120 msec).
  14. Had a Tisdale risk score ≥11 without the ability to monitor with serial electrocardiograms (ECGs) or telemetry.
  15. Had severe renal impairment, as determined by calculated creatinine clearance <30 mL/min or estimated glomerular filtration rate (eGFR) <30 mL/min/1.73 m2.
  16. Had alanine aminotransferase (ALT) or aspartate aminotransferase (AST) values >5x upper limit of normal (ULN).
  17. Had activated partial thromboplastin time (aPTT) >42 seconds.
  18. Had thrombocytopenia with a platelet count <80,000/mm3.
  19. Had severe chronic liver disease (Child-Pugh Score of 10 to 15).
  20. Had received dociparstat in a different clinical study.
  21. Woman of childbearing potential who was pregnant, breastfeeding, and/or not using a highly-effective method of contraception (consistent with local regulations regarding the methods of contraception for those participating in clinical studies).
  22. Had evidence of clinical improvement in COVID-19 status including, but not limited to, a sustained reduction in oxygen requirements over the previous 48 hours, or extubated and/or no longer requiring mechanical ventilation following intubation for COVID-19.
  23. Had any other condition, including abnormal laboratory values, that, in the judgment of the Investigator, could have put the participant at increased risk, or would have interfered with the conduct or planned analysis of the study.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 85 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04389840
Other Study ID Numbers  ICMJE CMX-DS-004
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
Current Responsible Party Chimerix
Original Responsible Party Same as current
Current Study Sponsor  ICMJE Chimerix
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Chimerix
Verification Date August 2022

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