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

NCT04389840 | Terminated Phase 2 Results DMC FDA Drug

• 1 other identifier: CMX-DS-004
• Study Type: interventional
• Target: 27
• Locations: 1 country
• Sites: 12

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.

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

Outcome Measures

Primary Outcomes (1)

• Number of Participants Who Are Alive and Free of Invasive Mechanical Ventilation or ECMO Through Day 28

  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.

  Day 1 to Day 28 (28 days)

Study Arms (6)

Cohort 1 dociparstat

EXPERIMENTAL

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 \[168 hours\]).

Drug: Dociparstat sodium

Cohort 1 placebo

PLACEBO COMPARATOR

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 \[168 hours\])

Drug: Placebo

Cohort 2 dociparstat

EXPERIMENTAL

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 \[168 hours\]).

Drug: Dociparstat sodium

Cohort 2 placebo

PLACEBO COMPARATOR

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 \[168 hours\]).

Drug: Placebo

Cohort 3 dociparstat

EXPERIMENTAL

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 \[168 hours\]).

Drug: Dociparstat sodium

Cohort 3 placebo

PLACEBO COMPARATOR

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 \[168 hours\]).

Drug: Placebo

Interventions

Dociparstat sodium DRUG

Dociparstat is a glycosaminoglycan derived from porcine heparin.

Also known as: DSTAT, CX-01, 2-0,3-0 desulfated heparin, ODSH

Cohort 1 dociparstat; Cohort 2 dociparstat; Cohort 3 dociparstat

Placebo DRUG

0.9% Normal Saline

Also known as: Normal saline, Sodium chloride 0.9%, 0.9% Normal Saline

Cohort 1 placebo; Cohort 2 placebo; Cohort 3 placebo

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• A potential participant must have met all the following criteria to be included in the study:
• 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 \[RT-PCR; or other commercial or public health assay\]).
• Was aged ≥18 years and ≤85 years.
• Had a resting oxygen saturation (SaO2) of \<94% while breathing ambient air.
• 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).
• Had provided informed consent to participate in the study (by participant or legally-acceptable representative).

You may not qualify if:

• A potential participant who met any of the following criteria was not eligible to participate in the study:
• Was currently receiving invasive mechanical ventilation (e.g., via an endotracheal tube) (score of 2 on NIAID ordinal scale).
• Had severe chronic respiratory disease, defined by any oxygen requirement prior to incident COVID-19.
• 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.
• 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.
• Was receiving systemic corticosteroids for a chronic condition.
• Was receiving chronic anticoagulation with warfarin or direct oral anticoagulants (e.g., rivaroxaban, dabigatran, apixaban, edoxaban).
• 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.
• 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.
• 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.
• Had a history of congestive heart failure requiring hospitalization.
• Had active pericarditis (based on clinical assessment).
• Had malignancy or other irreversible disease or condition for which 6-month mortality was estimated ≥50%.
• Had a corrected QT interval (QTc) \>500 msec (or \>530-550 msec in participants with QRS greater than \>120 msec).
• Had a Tisdale risk score ≥11 without the ability to monitor with serial electrocardiograms (ECGs) or telemetry.

Sponsors & Collaborators

• Jazz Pharmaceuticals: lead

Study Sites (12)

University of Alabama at Birmingham

Birmingham, Alabama, 35294, United States

Location

Advanced Pulmonary Research Institute/Wellington Regional Medical Center

Loxahatchee Groves, Florida, 33470, United States

Location

Augusta University

Augusta, Georgia, 30912, United States

Location

Our Lady of the Lake

Baton Rouge, Louisiana, 70808, United States

Location

Tulane University

New Orleans, Louisiana, 70112, United States

Location

University Medical Center

New Orleans, Louisiana, 70112, United States

Location

William Beaumont Hospital

Royal Oak, Michigan, 48073, United States

Location

Ascension Macomb-Oakland Cardiovascular Research

Warren, Michigan, 48072, United States

Location

Wake Forest Baptist Health

Winston-Salem, North Carolina, 27157, United States

Location

Texas Health Harris Methodist Hospital Fort Worth

Dallas, Texas, 76104, United States

Location

Ascension St. Francis Hospital

Milwaukee, Wisconsin, 53215, United States

Location

Ascension All Saints Hospital

Racine, Wisconsin, 53405, United States

Location

Related Publications (2)

• 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.

  PMID: 33108622 BACKGROUND

• 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.

  PMID: 35244208 DERIVED

MeSH Terms

Conditions

COVID-19; Acute Lung Injury

Interventions

Saline Solution; Sodium Chloride

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases; Lung Injury

Intervention Hierarchy (Ancestors)

Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations; Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Limitations and Caveats

Due to improvement in the Coronavirus Disease 2019 (COVID-19) pandemic and low subject accrual, study enrollment was prematurely terminated on 20 May 2021. Therefore, formal statistical analyses were not performed, and no conclusions can be drawn about docipartstat with regards to efficacy.

Results Point of Contact

• Title: Chief Medical Officer
• Organization: Chimerix, Inc.

dmoore@chimerix.com

919-806-1074

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Double-blind
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: The first 12 subjects were to be randomized 1:1 (dociparstat:placebo) All other subjects were to be randomized 2:1 (dociparstat:placebo)

Study Record Dates

• First Submitted: May 13, 2020
• First Posted: May 15, 2020
• Study Start: July 8, 2020
• Primary Completion: May 20, 2021
• Study Completion: May 20, 2021
• Last Updated: August 30, 2022
• Results First Posted: August 30, 2022

Record last verified: 2022-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (12)