Clinical trial NCT04404361: PRE-VENT Study in Hospitalized Patients With Severe COVID-19 With or Without Cancer
Official title: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: COVID19
COVID-19
COVID
Keywords: COVID19
COVID-19
COVID
Lead sponsor: CTI BioPharma
Sponsor class: INDUSTRY
First posted: 2020-05-27
Enrollment: 200
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: Inclusion Criteria:

1. 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).
2. Age ≥ 18 years
3. Platelet count ≥ 50,000/µL
4. If fertile, willing to use effective birth control methods during the study
5. Provision of informed consent within 96 hours after hospitalization

Exclusion Criteria:

1. In the opinion of the investigator, progression to death is imminent and inevitable within the next 24 hours, irrespective of the provision of treatments
2. Currently intubated or intubated between screening and randomization
3. Suspected active uncontrolled bacterial, fungal, viral, or other infection (besides COVID 19)
4. Prior allogenic hematopoietic stem cell transplantation
5. Active lung cancer or history of lung cancer within the past 12 months
6. Any active grade 2 or higher hemorrhage
7. Any active gastrointestinal or metabolic condition that could interfere with absorption of oral medication
8. Uncontrolled intercurrent illness that, in the judgment of the treating physician, would limit compliance with study requirements
9. Known seropositivity for human immunodeficiency virus with cluster of differentiation 4 (CD4) count \< 200/mm3 within 3 months prior to randomization
10. Pregnant or breastfeeding, or positive pregnancy test in a pre-dose examination
11. Concurrent enrollment in another interventional trial (investigational COVID-19 antiviral studies are permitted)
12. Serum creatinine \> 2.5 mg/dL
13. Total bilirubin \> 4× the upper limit of normal
14. QT corrected by the Fridericia method (QTcF) prolongation \> 480 msec
15. Known history of New York Heart Association Class II, III, or IV congestive heart failure prior to hospital admission
16. Known allergic reaction to any Janus kinase 2 (JAK2) inhibitor
17. Exposure to any JAK2 inhibitor within 28 days
18. 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
19. Treatment with cytoreductive chemotherapy administered within 14 days prior to randomization
20. Administration of an IL 1 or IL 6 blocking immunomodulatory agent (such as tocilizumab, canakinumab, sarilumab, anakinra) within 48 hours prior to randomization
21. 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.
22. Unable to ingest capsules or tablets at randomization

Primary outcomes:
measure: Percentage of Participants With Progression to IMV and/or ECMO or Death
timeFrame: Baseline to Day 28
Secondary outcomes:
measure: The Number of Ventilator-Free Days
timeFrame: Baseline to Day 28
measure: The Mortality Rate at Day 28
timeFrame: Baseline to Day 28
measure: The Mortality Rate at Day 15
timeFrame: Baseline to Day 15
measure: The Time to Improvement by at Least 2 Points Relative to Baseline on the 7-point Ordinal Scale of Clinical Status
timeFrame: Baseline, Day 8, 15, 22, and 28.
measure: The Clinical Status as Assessed by the 7-point Ordinal Scale of Clinical Status at Days 8, 15, 22, and 28
timeFrame: Baseline, Day 8, 15, 22, 28
measure: The Rate of Use of Immunomodulatory Agents as Treatment for COVID-19
timeFrame: Baseline to Day 28
Other outcomes:
Locations:
city: Orange
country: United States
facility: St. Jude Hospital Yorba Linda dba St. Joseph Heritage Healthcare
state: California
city: Jacksonville
country: United States
facility: Ascension St. Vincent's Riverside Hospital
state: Florida
city: Atlanta
country: United States
facility: Grady Memorial Hospital
state: Georgia
city: Indianapolis
country: United States
facility: St. Vincent Medical Group, Inc
state: Indiana
city: Baltimore
country: United States
facility: St. Agnes Healthcare
state: Maryland
city: Boston
country: United States
facility: Brigham and Women's Hospital
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: Detroit
country: United States
facility: Ascension St. John Hospital
state: Michigan
city: Novi
country: United States
facility: Ascension Providence Hospital - Novi Campus
state: Michigan
city: Southfield
country: United States
facility: Providence Cancer Institute
state: Michigan
city: Morristown
country: United States
facility: Atlantic Melanoma Center
state: New Jersey
city: Morristown
country: United States
facility: Overlook Medical Center
state: New Jersey
city: Pompton Plains
country: United States
facility: Chilton Medical Center
state: New Jersey
city: New York
country: United States
facility: Mount Sinai Medical Center
state: New York
city: Cincinnati
country: United States
facility: The Carl and Edyth Lindner Center for Research and Education at The Christ Hospital
state: Ohio
city: Tulsa
country: United States
facility: St. John Medical Center
state: Oklahoma
city: Philadelphia
country: United States
facility: Albert Einstein Medical Center
state: Pennsylvania
city: Providence
country: United States
facility: Rhode Island Hospital
state: Rhode Island
city: Providence
country: United States
facility: The Miriam Hospital
state: Rhode Island
city: Milwaukee
country: United States
facility: Ascension St. Francis Hospital
state: Wisconsin
city: Racine
country: United States
facility: Ascension All Saints
state: Wisconsin
Study officials:
References: