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

• ClinicalTrials.gov Identifier: NCT04389840
• Recruitment Status: Terminated
• First Posted: May 15, 2020
• Results First Posted: August 30, 2022
• Last Update Posted: August 30, 2022
• Sponsor: Chimerix
• Information provided by (Responsible Party): Chimerix

Tracking Information

• First Submitted Date: May 13, 2020
• First Posted Date: May 15, 2020
• Results First Submitted Date: May 27, 2022
• Results First Posted Date: August 30, 2022
• Last Update Posted Date: August 30, 2022
• Actual Study Start Date: July 8, 2020
• Actual Primary Completion Date: May 20, 2021 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (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 (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

• Current Secondary Outcome Measures: Not Provided

Original Secondary Outcome Measures (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: Dociparstat for the Treatment of Severe COVID-19 in Adults at High Risk of Respiratory Failure
• Official Title: 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: Interventional
• Study Phase: Phase 2; Phase 3

Study Design

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

• Coronavirus Disease 2019 (COVID-19)
• Acute Lung Injury
• Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)

Intervention

• 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

• 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 *

• Lasky JA, Fuloria J, Morrison ME, Lanier R, Naderer O, Brundage T, Melemed A. Design and Rationale of a Randomized, Double-Blind, Placebo-Controlled, Phase 2/3 Study Evaluating Dociparstat in Acute Lung Injury Associated with Severe COVID-19. Adv Ther. 2021 Jan;38(1):782-791. doi: 10.1007/s12325-020-01539-z. Epub 2020 Oct 27.
• Flumignan RL, Civile VT, Tinoco JDS, Pascoal PI, Areias LL, Matar CF, Tendal B, Trevisani VF, Atallah AN, Nakano LC. Anticoagulants for people hospitalised with COVID-19. Cochrane Database Syst Rev. 2022 Mar 4;3(3):CD013739. doi: 10.1002/14651858.CD013739.pub2.

Recruitment Information

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

Eligibility Criteria

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

• Sexes Eligible for Study: All

• Ages: 18 Years to 85 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT04389840
• Other Study ID Numbers: 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

• Plan to Share IPD: No

• Current Responsible Party: Chimerix
• Original Responsible Party: Same as current
• Current Study Sponsor: Chimerix
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Chimerix
• Verification Date: August 2022