Study of Varespladib in Patients Hospitalized With Severe COVID-19

NCT04969991 | Terminated Phase 2 Results DMC FDA Drug

• 2 other identifiers: OPX-PR-02W81XWH20C0066
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 7

Brief Summary

This is a 2-part, multi-center, randomized, double-blind, placebo-controlled, phase 2 study designed to evaluate the safety, tolerability, and efficacy of oral varespladib, in addition to standard of care, in patients hospitalized with severe COVID-19 caused by SARS-CoV-2.

Conditions

Coronavirus Disease 2019; Disease Caused by Severe Acute Respiratory Syndrome Coronavirus 2

Keywords

acute respiratory distress syndrome; varespladib; LY333013; severe acute respiratory syndrome coronavirus 2; coronavirus disease 2019; ARDS

Outcome Measures

Primary Outcomes (1)

• Proportion of Participants Alive and Free of Respiratory Failure at Day 28

  The proportion of respiratory failure-free surviving participants in each Part 2 treatment group at Day 28 will be analyzed using the Mantel-Haenszel stratum-weighted estimator with treatment as a factor. Respiratory failure is defined based on resource utilization requiring at least one of the following: * Endotracheal intubation and mechanical ventilation * Oxygen delivered by high-flow nasal cannula (\[HFNC\] heated, humidified, oxygen delivered via reinforced nasal cannula at flow rates \>20 L/min with fraction of delivered oxygen ≥0.5) * Noninvasive positive pressure ventilation * ECMO, or * Clinical diagnosis of respiratory failure (i.e., clinical need for one of the preceding therapies, but preceding therapies not able to be administered in setting because of resource limitation)

  Baseline to Day 28

Secondary Outcomes (7)

• Proportion of Subjects Using HFNC Within the First 28 Days After Randomization

  From randomization through Day 28

• Proportion of Subjects Using Noninvasive Respiratory Support Within the First 28 Days After Randomization

  From randomization through Day 28

• Proportion of Subjects Using Mechanical Ventilation Within the First 28 Days After Randomization

  From randomization through Day 28

• Number of Days of Oxygen Support Through Day 28 After Randomization

  From randomization through Day 28

• Proportion of Participants Remaining Free of Mechanical Ventilation or ECMO Throughout the 28 Days After Randomization

  From randomization through Day 28

Other Outcomes (5)

• Participant-reported Quality-of-life Assessment Using the 12-item Short Form Survey (SF-12) at Day 28 After Randomization

  Day 28

• Activity of sPLA2 Within Blood Samples Collected as Clinically Required From Treatment Initiation to Day 28 After Randomization

  From treatment initiation through Day 28

• Changes in PK Parameters: Area-under-the-curve (AUC)

  Day 1 through Day 3

Study Arms (6)

Varespladib: 250 mg QD + Placebo + placebo

EXPERIMENTAL

For 7 days, and in addition to institutional standard of care, participants will take 250 mg varespladib in the morning. In order to maintain the blind, they will also take 1 placebo tablet in the afternoon and 1 placebo tablet in the evening.

Drug: Varespladib; Drug: Placebo

Varespladib: 250 mg BID + placebo

EXPERIMENTAL

For 7 days, and in addition to institutional standard of care, participants will take 250 mg varespladib in the morning and in the evening. In order to maintain the blind, they will also take 1 placebo tablet in the afternoon.

Drug: Varespladib; Drug: Placebo

Varespladib: 250 mg TID

EXPERIMENTAL

For 7 days, and in addition to institutional standard of care, participants will take 250 mg varespladib in the morning, in the afternoon, and in the evening.

Drug: Varespladib

Placebo

PLACEBO COMPARATOR

For 7 days, and in addition to institutional standard of care, participants will take 1 placebo tablet in the morning, in the afternoon, and in the evening.

Drug: Placebo

Varespladib: 250mg BID (Part 2 of trial)

EXPERIMENTAL

Dose chosen for Part 2 was twice a day dosing. For 7 days, and in addition to institutional standard of care, participants will take 250 mg varespladib in the morning, and in the evening.

Drug: Varespladib

Placebo (Part 2 of trial)

PLACEBO COMPARATOR

For 7 days, and in addition to institutional standard of care, participants will take 1 placebo tablet in the morning, and in the afternoon.

Drug: Placebo

Interventions

Varespladib DRUG

250 mg immediate-release oblong, white, film-coated tablet for oral administration

Also known as: LY333013

Varespladib: 250 mg BID + placebo; Varespladib: 250 mg QD + Placebo + placebo; Varespladib: 250 mg TID; Varespladib: 250mg BID (Part 2 of trial)

Placebo DRUG

Oral formulation matched to the oral varespladib tablet

Placebo; Placebo (Part 2 of trial); Varespladib: 250 mg BID + placebo; Varespladib: 250 mg QD + Placebo + placebo

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participant is hospitalized with severe COVID-19 illness, defined in accordance with the Food and Drug Administration (FDA) Guidance for Industry - COVID-19: Developing Drugs and Biological Products for Treatment or Prevention (May 2020):
• a. Severe illness:
• i. Symptoms suggestive of severe systemic illness with COVID-19, which could include any symptom of moderate illness or shortness of breath at rest, or respiratory distress
• ii. Clinical signs indicative of severe systemic illness with COVID-19, such as respiratory rate ≥30 per minute, heart rate ≥125 per minute, SpO₂ ≤93% on room air at sea level or partial pressure of oxygen PaO₂/fraction of inspired oxygen FiO₂ \<300.
• Participant has a positive virologic nucleic acid amplification test (NAAT) indicating SARS-CoV-2 infection in a sample collected \<72 hours prior to randomization.
• Participant is between the ages of 18 and 80 years at the time of enrollment.
• Participant provides informed consent prior to initiation of any study procedures.
• Participant agrees to not participate in another clinical trial for the treatment of COVID 19 or SARS-CoV-2 through Day 28.
• Participant has adequate hematologic status (in the absence of transfusion and growth factor support for at least 28 days), defined as follows:
• Absolute neutrophil count (ANC) ≥1.5 × 10⁹/L
• Platelet count ≥75 × 10⁹/L
• Hemoglobin ≥9 g/dL.
• Participant has an Eastern Cooperative Oncology Group (ECOG) performance score of 0-2.

You may not qualify if:

• Participant has mild, moderate, or critical COVID-19 defined in accordance with the FDA Guidance for Industry:
• a. Mild COVID-19:
• i. Symptoms of mild illness with COVID-19 that could include fever, cough, sore throat, malaise, headache, muscle pain, gastrointestinal symptoms, without shortness of breath or dyspnea
• ii. No clinical signs indicative of moderate, severe, or critical severity
• b. Moderate COVID-19:
• i. Symptoms of moderate illness with COVID-19, which could include any symptom of mild illness (fever, cough, sore throat, malaise, headache, muscle pain, gastrointestinal symptoms) or shortness of breath with exertion
• ii. Clinical signs suggestive of moderate illness with COVID-19, such as respiratory rate ≥20 breaths per minute, peripheral oxygen saturation (SpO₂) \>93% on room air at sea level, heart rate ≥90 beats per minute
• iii. No clinical signs indicative of severe or critical illness
• c. Critical COVID-19:
• i. Respiratory failure defined based on resource utilization requiring at least one of the following:
• Endotracheal intubation and mechanical ventilation
• Oxygen delivered by high-flow nasal cannula (\[HFNC\] heated, humidified, oxygen delivered via reinforced nasal cannula at flow rates \>20 L/min with fraction of delivered oxygen ≥0.5)
• Noninvasive positive pressure ventilation
• ECMO, or
• Clinical diagnosis of respiratory failure (i.e., clinical need for one of the preceding therapies, but preceding therapies not able to be administered in setting of resource limitation)

Sponsors & Collaborators

• Ophirex, Inc.: lead
• Premier Research: collaborator

Study Sites (7)

Ventura Clinical Trials

Ventura, California, 93003, United States

Location

University of Miami Miller School of Medicine

Miami, Florida, 33136, United States

Location

Westchester Research Center at Westchester General Hospital

Miami, Florida, 33155, United States

Location

Franciscan Alliance

Munster, Indiana, 46321, United States

Location

The Brigham and Women's Hospital Emergency Medicine

Boston, Massachusetts, 02115, United States

Location

Cooper University Hospital

Camden, New Jersey, 08103, United States

Location

Ascension St. John Clinical Research Institute

Tulsa, Oklahoma, 74104, United States

Location

Related Publications (11)

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• Englert JA, Bobba C, Baron RM. Integrating molecular pathogenesis and clinical translation in sepsis-induced acute respiratory distress syndrome. JCI Insight. 2019 Jan 24;4(2):e124061. doi: 10.1172/jci.insight.124061.

  PMID: 30674720 BACKGROUND

• Mirastschijski U, Dembinski R, Maedler K. Lung Surfactant for Pulmonary Barrier Restoration in Patients With COVID-19 Pneumonia. Front Med (Lausanne). 2020 May 22;7:254. doi: 10.3389/fmed.2020.00254. eCollection 2020. No abstract available.

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• Griffiths MJD, McAuley DF, Perkins GD, Barrett N, Blackwood B, Boyle A, Chee N, Connolly B, Dark P, Finney S, Salam A, Silversides J, Tarmey N, Wise MP, Baudouin SV. Guidelines on the management of acute respiratory distress syndrome. BMJ Open Respir Res. 2019 May 24;6(1):e000420. doi: 10.1136/bmjresp-2019-000420. eCollection 2019.

  PMID: 31258917 BACKGROUND

• Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, Zhang L, Fan G, Xu J, Gu X, Cheng Z, Yu T, Xia J, Wei Y, Wu W, Xie X, Yin W, Li H, Liu M, Xiao Y, Gao H, Guo L, Xie J, Wang G, Jiang R, Gao Z, Jin Q, Wang J, Cao B. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020 Feb 15;395(10223):497-506. doi: 10.1016/S0140-6736(20)30183-5. Epub 2020 Jan 24.

  PMID: 31986264 BACKGROUND

• Wang D, Hu B, Hu C, Zhu F, Liu X, Zhang J, Wang B, Xiang H, Cheng Z, Xiong Y, Zhao Y, Li Y, Wang X, Peng Z. Clinical Characteristics of 138 Hospitalized Patients With 2019 Novel Coronavirus-Infected Pneumonia in Wuhan, China. JAMA. 2020 Mar 17;323(11):1061-1069. doi: 10.1001/jama.2020.1585.

  PMID: 32031570 BACKGROUND

• Yang X, Yu Y, Xu J, Shu H, Xia J, Liu H, Wu Y, Zhang L, Yu Z, Fang M, Yu T, Wang Y, Pan S, Zou X, Yuan S, Shang Y. Clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia in Wuhan, China: a single-centered, retrospective, observational study. Lancet Respir Med. 2020 May;8(5):475-481. doi: 10.1016/S2213-2600(20)30079-5. Epub 2020 Feb 24.

  PMID: 32105632 BACKGROUND

• Gandhi RT, Lynch JB, Del Rio C. Mild or Moderate Covid-19. N Engl J Med. 2020 Oct 29;383(18):1757-1766. doi: 10.1056/NEJMcp2009249. Epub 2020 Apr 24. No abstract available.

  PMID: 32329974 BACKGROUND

• Abraham E, Naum C, Bandi V, Gervich D, Lowry SF, Wunderink R, Schein RM, Macias W, Skerjanec S, Dmitrienko A, Farid N, Forgue ST, Jiang F. Efficacy and safety of LY315920Na/S-5920, a selective inhibitor of 14-kDa group IIA secretory phospholipase A2, in patients with suspected sepsis and organ failure. Crit Care Med. 2003 Mar;31(3):718-28. doi: 10.1097/01.CCM.0000053648.42884.89.

  PMID: 12626975 BACKGROUND

• Ware J Jr, Kosinski M, Keller SD. A 12-Item Short-Form Health Survey: construction of scales and preliminary tests of reliability and validity. Med Care. 1996 Mar;34(3):220-33. doi: 10.1097/00005650-199603000-00003.

  PMID: 8628042 BACKGROUND

• Food and Drug Administration. Guidance for Industry on COVID-19: Developing Drugs and Biological Products for Treatment or Prevention, May 2020.

  BACKGROUND

Related Links

• COVID-19 Clinical management: living guidance
• In patients of COVID-19, what are the symptoms and clinical features of mild and moderate cases?

MeSH Terms

Conditions

COVID-19; Respiratory Distress Syndrome

Interventions

varespladib; varespladib methyl

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; Respiration Disorders

Results Point of Contact

• Title: Tim Platts-Mills, Chief Medical Officer
• Organization: Ophirex, Inc.

tim@ophirex.com

5592406073

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• 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: All participants, investigators, and study personnel involved in the conduct of the study, including data management, will be blinded to treatment assignment with the exception of a specified unblinded statistician, an unblinded pharmacist at each clinical site, a programmer from the contract research organization (CRO) who will have access to the randomization code, and the DSMB.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: The study will be conducted in 2 parts. Both parts will be randomized and double-blind. Part 1 will be dose-finding in 4 parallel treatment groups randomized to treatment with varespladib (at 250 mg once daily \[QD\], twice daily \[BID\], or three times daily \[TID\] \[total doses of 250, 500, or 750 mg/day\]) or placebo in a 5:5:5:3 ratio. After all participants in Part 1 have completed Day 28, a data safety monitoring board (DSMB) will review the safety results from Part 1 and will recommend the dose regimen to be used in Part 2. Part 2 will randomize an additional 72 participants to the dose regimen selected from Part 1 or placebo in a 1:1 ratio. In both parts of the study, eligible participants will be enrolled and randomized to receive either varespladib or placebo in addition to institutional standard of care for 7 days.

Study Record Dates

• First Submitted: July 8, 2021
• First Posted: July 21, 2021
• Study Start: June 30, 2021
• Primary Completion: February 11, 2022
• Study Completion: November 22, 2022
• Last Updated: May 15, 2025
• Results First Posted: May 15, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (7)