Clinical trial NCT04389840: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
PHASE3
Conditions: Coronavirus Disease 2019 (COVID-19)
Acute Lung Injury
Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)
Keywords: COVID-19
ALI
SARS-CoV-2
Lead sponsor: Chimerix
Sponsor class: INDUSTRY
First posted: 2020-05-15
Enrollment: 27
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
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)
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Number of Participants Who Are Alive and Free of Invasive Mechanical Ventilation or ECMO Through Day 28
timeFrame: Day 1 to Day 28 (28 days)
Secondary outcomes:
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Loxahatchee Groves
country: United States
facility: Advanced Pulmonary Research Institute/Wellington Regional Medical Center
state: Florida
city: Augusta
country: United States
facility: Augusta University
state: Georgia
city: Baton Rouge
country: United States
facility: Our Lady of the Lake
state: Louisiana
city: New Orleans
country: United States
facility: Tulane University
state: Louisiana
city: New Orleans
country: United States
facility: University Medical Center
state: Louisiana
city: Royal Oak
country: United States
facility: William Beaumont Hospital
state: Michigan
city: Warren
country: United States
facility: Ascension Macomb-Oakland Cardiovascular Research
state: Michigan
city: Winston-Salem
country: United States
facility: Wake Forest Baptist Health
state: North Carolina
city: Dallas
country: United States
facility: Texas Health Harris Methodist Hospital Fort Worth
state: Texas
city: Milwaukee
country: United States
facility: Ascension St. Francis Hospital
state: Wisconsin
city: Racine
country: United States
facility: Ascension All Saints Hospital
state: Wisconsin
Study officials:
References:
citation: 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.
citation: 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.