PRE-VENT Study in Hospitalized Patients With Severe COVID-19 With or Without Cancer

Study Overview
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Brief Summary
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This is a Phase 2 randomized, double-blind, placebo-controlled, multicenter study to evaluate the efficacy and safety of pacritinib in hospitalized patients with severe COVID-19 with or without cancer.

Detailed Description
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This is a Phase 2 randomized, double-blind, placebo-controlled, multicenter study to evaluate the efficacy and safety of pacritinib in hospitalized patients with severe COVID-19 with or without cancer. Severe COVID-19 is defined as confirmed disease in patients who are hospitalized with hypoxia (blood oxygen saturation [SpO2] ≤93% on room air at sea level), respiratory rate >30, arterial oxygen partial pressure [PaO2]/ fraction of inspired oxygen [FiO2] <300, or lung infiltrates >50% but do not require IMV. Patients will be randomized 1:1 to receive pacritinib (400 mg once daily [QD] on Day 1, then 200 mg twice daily [BID] from Day 2 to Day 14) + SOC or placebo + SOC. Assigned treatment will continue for up to Day 14 or until the patient experiences intolerable adverse events (AEs), withdraws consent, or initiates another investigational therapy or until the study is terminated. Assigned therapy may be given for an additional 7 days (for a total of 21 days) with the approval of the Medical Monitor if, in the opinion of the investigator, the patient's clinical signs and symptoms are improving and the potential benefit outweighs the potential risk.In the event of hospital discharge, patients will complete treatment with the assigned therapy as an outpatient.

Official Title
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A Phase 2 Randomized, Double-blind, Placebo-controlled, Multicenter Study of Pacritinib Plus Standard of Care Versus Placebo and Standard of Care in Hospitalized Patients With Severe COVID-19 With or Without Cancer

Conditions
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COVID19, COVID-19, COVID

Intervention / Treatment
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* Drug: Pacritinib
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Hospitalized or will be hospitalized prior to randomization for the treatment of severe COVID-19 with SARS-CoV-2 infection confirmed by either a) a positive reverse transcriptase polymerase chain reaction (RT PCR) or b) an antigen-based test from any respiratory, nasopharyngeal, saliva, blood, or stool specimen at Screening or documented within 1 week prior to the start of Screening (Severe COVID-19 is defined as confirmed disease in patients who are hospitalized with hypoxia [SpO2 ≤93% on room air], respiratory rate >30, PaO2/FiO2 <300, but do not require IMV). Age ≥ 18 years Platelet count ≥ 50,000/µL If fertile, willing to use effective birth control methods during the study Provision of informed consent within 96 hours after hospitalization Exclusion Criteria: In the opinion of the investigator, progression to death is imminent and inevitable within the next 24 hours, irrespective of the provision of treatments Currently intubated or intubated between screening and randomization Suspected active uncontrolled bacterial, fungal, viral, or other infection (besides COVID 19) Prior allogenic hematopoietic stem cell transplantation Active lung cancer or history of lung cancer within the past 12 months Any active grade 2 or higher hemorrhage Any active gastrointestinal or metabolic condition that could interfere with absorption of oral medication Uncontrolled intercurrent illness that, in the judgment of the treating physician, would limit compliance with study requirements Known seropositivity for human immunodeficiency virus with cluster of differentiation 4 (CD4) count < 200/mm3 within 3 months prior to randomization Pregnant or breastfeeding, or positive pregnancy test in a pre-dose examination Concurrent enrollment in another interventional trial (investigational COVID-19 antiviral studies are permitted) Serum creatinine > 2.5 mg/dL Total bilirubin > 4× the upper limit of normal QT corrected by the Fridericia method (QTcF) prolongation > 480 msec Known history of New York Heart Association Class II, III, or IV congestive heart failure prior to hospital admission Known allergic reaction to any Janus kinase 2 (JAK2) inhibitor Exposure to any JAK2 inhibitor within 28 days Currently receiving a strong CYP3A4 inhibitor or strong P450 inducer (Appendix 1 and Appendix 2, respectively) and unable to stop the medication prior to the first dose of study drug and throughout the duration of study drug administration Treatment with cytoreductive chemotherapy administered within 14 days prior to randomization Administration of an IL 1 or IL 6 blocking immunomodulatory agent (such as tocilizumab, canakinumab, sarilumab, anakinra) within 48 hours prior to randomization Currently receiving therapeutic anticoagulation or anti platelet medication and unable to stop the medication prior to randomization. Prophylactic anticoagulation therapy or aspirin (≤ 100mg) are permitted. Unable to ingest capsules or tablets at randomization

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Pacritinib and SOC<br>Pacritinib 400 mg once daily [QD] on Day 1, then 200 mg twice daily [BID] from Day 2 to Day 14) + SOC | Drug: Pacritinib<br>* 100 mg capsules<br>* Other names: Oral Csf1 inhibitor;|
| Placebo Comparator: Placebo and SOC<br>4 capsules once daily [QD] on Day 1, then 2 capsules twice daily [BID] from Day 2 to Day 14) + SOC | Drug: Placebo<br>* Placebo capsules matching pacritinib 100 mg capsules<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of patients who progress to IMV and/or ECMO or death during the 28 days following randomization | The proportion is calculated as the number of patients who progress divided by the total number of patients in the ITT population. | 28 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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COVID19, COVID-19, COVID