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

NCT ID: NCT04389840

Last Updated: 2022-08-30

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 27 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-07-08
• Study Completion Date: 2021-05-20

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.

Conditions

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

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 \[168 hours\]).

Group Type: EXPERIMENTAL

Dociparstat sodium

Intervention Type: DRUG

Dociparstat is a glycosaminoglycan derived from porcine heparin.

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 \[168 hours\])

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

0.9% Normal Saline

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 \[168 hours\]).

Group Type: EXPERIMENTAL

Dociparstat sodium

Intervention Type: DRUG

Dociparstat is a glycosaminoglycan derived from porcine heparin.

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 \[168 hours\]).

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

0.9% Normal Saline

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 \[168 hours\]).

Group Type: EXPERIMENTAL

Dociparstat sodium

Intervention Type: DRUG

Dociparstat is a glycosaminoglycan derived from porcine heparin.

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 \[168 hours\]).

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

0.9% Normal Saline

Interventions

Dociparstat sodium

Dociparstat is a glycosaminoglycan derived from porcine heparin.

Intervention Type: DRUG

Placebo

0.9% Normal Saline

Intervention Type: DRUG

Other Intervention Names

DSTAT; CX-01; 2-0,3-0 desulfated heparin; ODSH; Normal saline; Sodium chloride 0.9%; 0.9% Normal Saline

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 85 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Jazz Pharmaceuticals

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

University of Alabama at Birmingham

Birmingham, Alabama, United States

Advanced Pulmonary Research Institute/Wellington Regional Medical Center

Loxahatchee Groves, Florida, United States

Augusta University

Augusta, Georgia, United States

Our Lady of the Lake

Baton Rouge, Louisiana, United States

Tulane University

New Orleans, Louisiana, United States

University Medical Center

New Orleans, Louisiana, United States

William Beaumont Hospital

Royal Oak, Michigan, United States

Ascension Macomb-Oakland Cardiovascular Research

Warren, Michigan, United States

Wake Forest Baptist Health

Winston-Salem, North Carolina, United States

Texas Health Harris Methodist Hospital Fort Worth

Dallas, Texas, United States

Ascension St. Francis Hospital

Milwaukee, Wisconsin, United States

Ascension All Saints Hospital

Racine, Wisconsin, United States

Countries

United States

References

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.

Reference Type: BACKGROUND

PMID: 33108622 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 35244208 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

CMX-DS-004

Identifier Type: -

Identifier Source: org_study_id