Coronavirus Disease 2019Phase 2STAIRSNCT04969991
Study of Varespladib in Patients Hospitalized With Severe COVID-19
A Phase 2 study testing Varespladib in people with Coronavirus Disease 2019 and Disease Caused by Severe Acute Respiratory Syndrome Coronavirus 2, run by Ophirex, Inc. at 7 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Coronavirus Disease 2019, Disease Caused by Severe Acute Respiratory Syndrome Coronavirus 2
- What is being tested?
- Varespladib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 18 participants
- Where
- 7 sitesUnited States
- Study dates
- 30 Jun 2021to 22 Nov 2022
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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):
- Severe illness:
- 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
- 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.
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- 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.
Who cannot join
- Participant has mild, moderate, or critical COVID-19 defined in accordance with the FDA Guidance for Industry:
- Mild COVID-19:
- 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
- No clinical signs indicative of moderate, severe, or critical severity
- Moderate COVID-19:
- 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
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- 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
- No clinical signs indicative of severe or critical illness
- Critical COVID-19:
- 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)
- Shock (defined by systolic blood pressure <90 mmHg, or diastolic blood pressure <60 mmHg or requiring vasopressors)
- Multi-organ dysfunction/failure.
- Participant has taken investigational medications within 7 days or 5 half-lives prior to enrollment, whichever is shorter.
- Participant has required any new form of sedation, anxiolysis or central nervous system (CNS) depressant within the 48 hours prior to enrollment that would interfere with neurologic assessments at enrollment.
- Has history of cerebrovascular accident or intracranial bleeding of any kind, acute coronary syndrome, myocardial infarction, or severe pulmonary hypertension.
- Participant has chronic respiratory failure not associated with COVID-19, defined as prior need for home oxygen, need for home noninvasive positive-pressure ventilation (NIPPV) for reasons other than isolated sleep apnea, or other signs of chronic respiratory failure, in the investigator's judgment.
- Upper gastrointestinal (GI) bleed evidenced by hematemesis, "coffee-ground" emesis or nasogastric aspirate, or hematochezia thought to originate from upper GI tract.
- Participant has abnormal liver function defined as any 2 of the following at screening:
- Total bilirubin ≥2 × ULN
- Alanine aminotransferase (ALT) ≥3 × ULN
- Aspartate aminotransferase (AST) ≥3 × ULN
- Alkaline phosphatase (ALP) >3 × ULN
- Gamma-glutamyl transferase (GGT) >3 × ULN
- Participant has an estimated glomerular filtration rate (eGFR) <60 mL/min.
- Participant has a known allergy or significant adverse reaction to varespladib-methyl or related compounds.
- Participant is considered by the investigator to be unable to comply with protocol requirements due to geographic considerations, psychiatric disorders, or other compliance concerns; or has any serious medical condition or clinically significant laboratory, ECG, vital sign, or physical examination abnormality that would prevent study participation or place the participant at significant risk, as judged by the Investigator.
- Participant is breast-feeding, pregnant, has a positive serum hCG pregnancy test, or is not willing to use a highly effective method of contraception for 14 days after treatment. Highly effective methods of contraception are as follows:
- Combined (estrogen- and progestogen-containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal, or transdermal)
- Progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable, or implantable)
- Intrauterine device, intrauterine hormone-releasing system
- Bilateral tubal occlusion
- Vasectomized partner
- Sexual abstinence
- Double-barrier method (condoms, sponge, diaphragm, with spermicidal jellies, or cream).
Trial locations and contacts
7 sites in 1 country.
7 sites in 1 country
United States7 sites
The Brigham and Women's Hospital Emergency Medicine
Boston, Massachusetts, 02115
Cooper University Hospital
Camden, New Jersey, 08103
University of Miami Miller School of Medicine
Miami, Florida, 33136
Westchester Research Center at Westchester General Hospital
Miami, Florida, 33155
Franciscan Alliance
Munster, Indiana, 46321
Ascension St. John Clinical Research Institute
Tulsa, Oklahoma, 74104
Ventura Clinical Trials
Ventura, California, 93003
About this study
Official title: A Phase 2, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Safety, Tolerability, and Efficacy of Varespladib in Patients Hospitalized With Severe COVID 19 Caused by SARS-CoV-2
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.
Read the detailed description
The goals of this 2-part, multi-center, randomized, double-blind, placebo-controlled, phase 2 study are to define a safe dose for the population and to assess the safety, tolerability, and efficacy of orally dosed varespladib to improve survival without respiratory failure in patients hospitalized with severe coronavirus disease 2019 (COVID-19), when given in addition to the institutional standard of care therapy.
Mortality rates of COVID-19 are strongly linked to acute respiratory distress syndrome (ARDS) which may be, additionally, correlated with elevations of secretory phospholipase 2 (sPLA2) and widespread loss of functioning lung tissue. Upregulation of sPLA2 is thought to be involved in the dysregulated inflammatory cascade pathways (increased markers of immune activation, also known as cytokine release syndrome) and enzymatic degradation of lung surfactant linked to the development of ARDS. It is believed that treatment with varespladib, a potent inhibitor of sPLA2, might prevent or mitigate progression of pulmonary dysfunction in COVID-19 patients by two mechanisms: suppression of sPLA2-induced inflammation and, uniquely, preservation of pulmonary surfactant by direct inhibition of the enzyme responsible for surfactant phospholipid degradation: sPLA2.
Data from previous phase 2 clinical trials of varespladib suggested it had potential to reduce mortality in severely septic patients with ARDS, particularly when treatment was initiated within 18 hours of identification of organ failure.
The study will be conducted in two parts. Both parts will be randomized and double-blind. Part 1 will be dose-finding in four parallel treatment groups randomized to treatment with varespladib (at 250 mg once daily [QD], twice daily [BID], or three times daily [TID] [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, including all available safety data through Day 60, 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 active varespladib or placebo in addition to institutional standard of care for 7 days.
Participants will be assessed daily per standard of care while hospitalized and on a regular basis after discharge. The Day 1, 4, 7, 14, and 28 visits will be performed in person (either at the hospital/site or via a home health provider) to assess safety, obtain blood and urine samples for laboratory tests, and obtain clinical outcome data. The Day 2, 3, 5, 6, 8, 9, 10, 11, 12, 13, 15, 16, 17, 18, 19, 20, 21, 45, and 60 visits for discharged participants may be conducted by phone or via electronic patient-reported outcome (ePRO) devices.
Efficacy will be assessed by respiratory failure-free survival at Day 28. Safety will be assessed by evaluating adverse events (AEs), vital sign measurements, use of oxygen therapies, changes in levels of biomarkers, clinical laboratory test results, electrocardiograms (ECGs), physical examination findings, and concomitant medications and therapies. A DSMB will evaluate safety data at specified intervals during both parts of the trial.
Pharmacokinetic (PK) samples will be drawn from all participants in Part 1 and in a subset of approximately 14 participants in Part 2 in order to enable estimation of PK parameters in approximately 22 participants receiving active treatment with varespladib.
- Conditions
- Coronavirus Disease 2019, Disease Caused by Severe Acute Respiratory Syndrome Coronavirus 2
- Being tested
- Varespladib, Placebo
- Keywords
- acute respiratory distress syndrome, varespladib, LY333013, severe acute respiratory syndrome coronavirus 2, coronavirus disease 2019, ARDS
- Medical subject headings
- COVID-19, Respiratory Distress Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
VarespladibDrug
Also called LY333013
250 mg immediate-release oblong, white, film-coated tablet for oral administration
PlaceboDrug
Oral formulation matched to the oral varespladib tablet
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: 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. Receives: 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. Receives: 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. Receives: 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. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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)
Measured: Baseline to Day 28
Secondary outcomes (7)
Proportion of Subjects Using HFNC Within the First 28 Days After Randomization
The proportion of subjects using HFNC within the first 28 days after randomization.
Measured: From randomization through Day 28
Proportion of Subjects Using Noninvasive Respiratory Support Within the First 28 Days After Randomization
Proportion of subjects using noninvasive respiratory support within the first 28 days after randomization.
Measured: From randomization through Day 28
Proportion of Subjects Using Mechanical Ventilation Within the First 28 Days After Randomization
Proportion of subjects using mechanical ventilation within the first 28 days after randomization.
Measured: From randomization through Day 28
Number of Days of Oxygen Support Through Day 28 After Randomization
Number of days of oxygen support through Day 28 after randomization.
Measured: From randomization through Day 28
Proportion of Participants Remaining Free of Mechanical Ventilation or ECMO Throughout the 28 Days After Randomization
Proportion of participants remaining free of mechanical ventilation or ECMO throughout the 28 days after randomization.
Measured: From randomization through Day 28
Proportion of Subjects With All-cause Mortality Through Day 60
Proportion of subjects who experience all-cause mortality from randomization through Day 60.
Measured: From randomization through Day 60
Number of Participants With Change in Body Temperature
Number of participants with change in body temperature from providing informed consent through Day 60.
Measured: From providing informed consent through Day 60
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Jul 2021
- Study start30 Jun 2021
- Primary completion11 Feb 2022
- Study completion22 Nov 2022
Why it stopped: Part 2 of the study was paused on 03-May-2022 due to slow enrollment following low infection rates and hospitalizations of patients with severe COVID-19, and did not recommence prior to study closure (early termination) on 22-Nov-2022.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (11)Papers the sponsor has linked to this study.
- Other trials for Coronavirus Disease 2019Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- 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.
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 18 participants (actual)
Sponsor and investigators
- Lead sponsor
- Ophirex, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Premier Research
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04969991
- Sponsor's protocol ID
- OPX-PR-02
- Other IDs
- W81XWH20C0066
- Acronym
- STAIRS
- Status last verified
- Apr 2025
- First submitted
- 8 Jul 2021
- Last updated
- 15 May 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Rezoagli E, Fumagalli R, Bellani G. Definition and epidemiology of acute respiratory distress syndrome. Ann Transl Med. 2017 Jul;5(14):282. doi: 10.21037/atm.2017.06.62.
PubMed 28828357Englert 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.
PubMed 30674720Mirastschijski 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.
PubMed 32574339Griffiths 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.
PubMed 31258917Huang 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.
PubMed 31986264Wang 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.
PubMed 32031570Yang 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.
PubMed 32105632Gandhi 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.
PubMed 32329974Abraham 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.
PubMed 12626975Ware 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.
PubMed 8628042Food and Drug Administration. Guidance for Industry on COVID-19: Developing Drugs and Biological Products for Treatment or Prevention, May 2020.
Study at a glance
From the registry record, last updated by the sponsor on 15 May 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 2, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Safety, Tolerability, and Efficacy of Varespladib in Patients Hospitalized With Severe COVID 19 Caused by SARS-CoV-2
- ClinicalTrials.gov ID
- NCT04969991
- Acronym / sponsor ID
- STAIRS / OPX-PR-02
- 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
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Part 2 of the study was paused on 03-May-2022 due to slow enrollment following low infection rates and hospitalizations of patients with severe COVID-19, and did not recommence prior to study closure (early termination) on 22-Nov-2022.
- Enrolment
- 18 participants (actual)
- Lead sponsor
- Ophirex, Inc.Industry (pharma, biotech, devices)
- Collaborators
- Premier Research
- Study start
- 30 Jun 2021 (actual)
- Primary completion
- 11 Feb 2022 (actual)
- Study completion
- 22 Nov 2022 (actual)
- First posted
- 21 Jul 2021 (actual)
- Results
- Posted 15 May 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
The goals of this 2-part, multi-center, randomized, double-blind, placebo-controlled, phase 2 study are to define a safe dose for the population and to assess the safety, tolerability, and efficacy of orally dosed varespladib to improve survival without respiratory failure in patients hospitalized with severe coronavirus disease 2019 (COVID-19), when given in addition to the institutional standard of care therapy.
Mortality rates of COVID-19 are strongly linked to acute respiratory distress syndrome (ARDS) which may be, additionally, correlated with elevations of secretory phospholipase 2 (sPLA2) and widespread loss of functioning lung tissue. Upregulation of sPLA2 is thought to be involved in the dysregulated inflammatory cascade pathways (increased markers of immune activation, also known as cytokine release syndrome) and enzymatic degradation of lung surfactant linked to the development of ARDS. It is believed that treatment with varespladib, a potent inhibitor of sPLA2, might prevent or mitigate progression of pulmonary dysfunction in COVID-19 patients by two mechanisms: suppression of sPLA2-induced inflammation and, uniquely, preservation of pulmonary surfactant by direct inhibition of the enzyme responsible for surfactant phospholipid degradation: sPLA2.
Data from previous phase 2 clinical trials of varespladib suggested it had potential to reduce mortality in severely septic patients with ARDS, particularly when treatment was initiated within 18 hours of identification of organ failure.
The study will be conducted in two parts. Both parts will be randomized and double-blind. Part 1 will be dose-finding in four parallel treatment groups randomized to treatment with varespladib (at 250 mg once daily [QD], twice daily [BID], or three times daily [TID] [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, including all available safety data through Day 60, 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 active varespladib or placebo in addition to institutional standard of care for 7 days.
Participants will be assessed daily per standard of care while hospitalized and on a regular basis after discharge. The Day 1, 4, 7, 14, and 28 visits will be performed in person (either at the hospital/site or via a home health provider) to assess safety, obtain blood and urine samples for laboratory tests, and obtain clinical outcome data. The Day 2, 3, 5, 6, 8, 9, 10, 11, 12, 13, 15, 16, 17, 18, 19, 20, 21, 45, and 60 visits for discharged participants may be conducted by phone or via electronic patient-reported outcome (ePRO) devices.
Efficacy will be assessed by respiratory failure-free survival at Day 28. Safety will be assessed by evaluating adverse events (AEs), vital sign measurements, use of oxygen therapies, changes in levels of biomarkers, clinical laboratory test results, electrocardiograms (ECGs), physical examination findings, and concomitant medications and therapies. A DSMB will evaluate safety data at specified intervals during both parts of the trial.
Pharmacokinetic (PK) samples will be drawn from all participants in Part 1 and in a subset of approximately 14 participants in Part 2 in order to enable estimation of PK parameters in approximately 22 participants receiving active treatment with varespladib.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 6
- Model description
- 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.
| Arm | Type | Receives |
|---|---|---|
| Varespladib: 250 mg QD + Placebo + placebo | Experimental | Drug: Varespladib, Drug: PlaceboFor 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. |
| Varespladib: 250 mg BID + placebo | Experimental | Drug: Varespladib, Drug: PlaceboFor 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. |
| Varespladib: 250 mg TID | Experimental | Drug: VarespladibFor 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. |
| Placebo | Placebo comparator | Drug: PlaceboFor 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. |
| Varespladib: 250mg BID (Part 2 of trial) | Experimental | Drug: VarespladibDose 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. |
| Placebo (Part 2 of trial) | Placebo comparator | Drug: PlaceboFor 7 days, and in addition to institutional standard of care, participants will take 1 placebo tablet in the morning, and in the afternoon. |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- 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):
- 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.
Key exclusion criteria (39 listed)
- Participant has mild, moderate, or critical COVID-19 defined in accordance with the FDA Guidance for Industry:
- Participant has taken investigational medications within 7 days or 5 half-lives prior to enrollment, whichever is shorter.
- Participant has required any new form of sedation, anxiolysis or central nervous system (CNS) depressant within the 48 hours prior to enrollment that would interfere with neurologic assessments at enrollment.
- Has history of cerebrovascular accident or intracranial bleeding of any kind, acute coronary syndrome, myocardial infarction, or severe pulmonary hypertension.
- Participant has chronic respiratory failure not associated with COVID-19, defined as prior need for home oxygen, need for home noninvasive positive-pressure ventilation (NIPPV) for reasons other than isolated sleep apnea, or other signs of chronic respiratory failure, in the investigator's judgment.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| VarespladibAlso: LY333013250 mg immediate-release oblong, white, film-coated tablet for oral administration | Drug | Varespladib: 250 mg BID + placebo, Varespladib: 250 mg QD + Placebo + placebo, Varespladib: 250 mg TID, Varespladib: 250mg BID (Part 2 of trial) |
| PlaceboOral formulation matched to the oral varespladib tablet | Drug | Placebo, Placebo (Part 2 of trial), Varespladib: 250 mg BID + placebo, Varespladib: 250 mg QD + Placebo + placebo |
Primary outcome
Proportion of Participants Alive and Free of Respiratory Failure at Day 28
Time frame: Baseline to 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)
7 secondary outcomes
Proportion of Subjects Using HFNC Within the First 28 Days After Randomization
Time frame: From randomization through Day 28
Proportion of Subjects Using Noninvasive Respiratory Support Within the First 28 Days After Randomization
Time frame: From randomization through Day 28
Proportion of Subjects Using Mechanical Ventilation Within the First 28 Days After Randomization
Time frame: From randomization through Day 28
Number of Days of Oxygen Support Through Day 28 After Randomization
Time frame: From randomization through Day 28
Proportion of Participants Remaining Free of Mechanical Ventilation or ECMO Throughout the 28 Days After Randomization
Time frame: From randomization through Day 28
Proportion of Subjects With All-cause Mortality Through Day 60
Time frame: From randomization through Day 60
Number of Participants With Change in Body Temperature
Time frame: From providing informed consent through Day 60
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 May 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 28828357Rezoagli E, Fumagalli R, Bellani G. Definition and epidemiology of acute respiratory distress syndrome. Ann Transl Med. 2017 Jul;5(14):282. doi: 10.21037/atm.2017.06.62.
- Background: PubMed 30674720Englert 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.
- Background: PubMed 32574339Mirastschijski 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.
- Background: PubMed 31258917Griffiths 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.
- Background: PubMed 31986264Huang 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.
- Background: PubMed 32031570Wang 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.
- Background: PubMed 32105632Yang 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.
- Background: PubMed 32329974Gandhi 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.
- Background: PubMed 12626975Abraham 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.
- Background: PubMed 8628042Ware 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.
- BackgroundFood and Drug Administration. Guidance for Industry on COVID-19: Developing Drugs and Biological Products for Treatment or Prevention, May 2020.
- COVID-19 Clinical management: living guidanceLink provided by the sponsor.
- In patients of COVID-19, what are the symptoms and clinical features of mild and moderate cases?Link provided by the sponsor.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
7 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Varespladib in people with Coronavirus Disease 2019 and Disease Caused by Severe Acute Respiratory Syndrome Coronavirus 2, run by Ophirex, Inc. at 7 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 13 inclusion and 39 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 15 May 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 7 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 15 May 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Proportion of Participants Alive and Free of Respiratory Failure at Day 28 (time frame: Baseline to Day 28). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04969991, which also lists 11 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 May 2025.