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

Phase 2

Terminated

• Conditions: COVID-19; COVID; COVID19
• Interventions: Drug: Placebo; Drug: Pacritinib

• Registration Number: NCT04404361
• Lead Sponsor: CTI BioPharma

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.

Study Timeline

• Study Start: 2020-05-22
• Study First Submitted: 2020-05-22
• Study First Submitted QC: 2020-05-22
• Study First Posted: 2020-05-27
• Primary Completion: 2021-09-21
• Study Completion: 2021-09-21
• Results First Submitted: 2024-02-09
• Status Verified: 2024-05
• Results First Submitted QC: 2024-05-07
• Last Update Submitted: 2024-05-07
• Results First Posted: 2024-06-05
• Last Update Posted: 2024-06-05

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 200

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo and SOC	Placebo	4 capsules once daily \[QD\] on Day 1, then 2 capsules twice daily \[BID\] from Day 2 to Day 14) + SOC
Pacritinib and SOC	Pacritinib	Pacritinib 400 mg once daily \[QD\] on Day 1, then 200 mg twice daily \[BID\] from Day 2 to Day 14) + SOC

Primary Outcome Measures

Name	Time	Method
Percentage of Participants With Progression to IMV and/or ECMO or Death	Baseline to Day 28	The percentage is calculated as the number of patients who progress to IMV/ECMO or death divided by the total number of patients in the ITT population (n/N \* 100).

Secondary Outcome Measures

Name	Time	Method
The Mortality Rate at Day 15	Baseline to Day 15	the number of patients with outcome of death in the 15 days following randomization
The Number of Ventilator-Free Days	Baseline to Day 28	the number of days that patients are alive and not intubated, from randomization to Day 28
The Mortality Rate at Day 28	Baseline to Day 28	the number of patients with outcome of death during the 28 days following randomization
The Clinical Status as Assessed by the 7-point Ordinal Scale of Clinical Status at Days 8, 15, 22, and 28	Baseline, Day 8, 15, 22, 28	Clinical status assessment based on the adapted scale from Cao et al. The patient CS is summarized by study visit.; STATUS: 1. not hospitalized with resumption of normal activities; 2. not hospitalized but unable to resume normal activities; 3. hospitalization, not requiring supplemental oxygen; 4. hospitalization, requiring supplemental oxygen not meeting the criteria for categories 5 or 6; 5. hospitalization, on non-invasive positive pressure ventilation or high-flow nasal cannula; 6. hospitalization, requiring IMV and/or ECMO; 7. death.
The Time to Improvement by at Least 2 Points Relative to Baseline on the 7-point Ordinal Scale of Clinical Status	Baseline, Day 8, 15, 22, and 28.	Time to Improvement (days) = Date of improvement - Date of randomization + 1. Date of Improvement was defined as the time to first ordinal scale assessment 2 points or more lower than the baseline clinical status assessment.
The Rate of Use of Immunomodulatory Agents as Treatment for COVID-19	Baseline to Day 28	the proportion of patients reporting use of medications such as corticosteroids, tocilizumab, anakinra, or eculizumab as treatment for COVID-19, during 28 days following randomization

Trial Locations

Locations (21)

St. Jude Hospital Yorba Linda dba St. Joseph Heritage Healthcare; 🇺🇸 Orange, California, United States

Overlook Medical Center; 🇺🇸 Morristown, New Jersey, United States

Ascension St. Vincent's Riverside Hospital; 🇺🇸 Jacksonville, Florida, United States

Mount Sinai Medical Center; 🇺🇸 New York, New York, United States

Ascension St. John Hospital; 🇺🇸 Detroit, Michigan, United States

Grady Memorial Hospital; 🇺🇸 Atlanta, Georgia, United States

Ascension Providence Hospital - Novi Campus; 🇺🇸 Novi, Michigan, United States

Providence Cancer Institute; 🇺🇸 Southfield, Michigan, United States

Albert Einstein Medical Center; 🇺🇸 Philadelphia, Pennsylvania, United States

St. Agnes Healthcare; 🇺🇸 Baltimore, Maryland, United States

The Carl and Edyth Lindner Center for Research and Education at The Christ Hospital; 🇺🇸 Cincinnati, Ohio, United States

St. John Medical Center; 🇺🇸 Tulsa, Oklahoma, United States

St. Vincent Medical Group, Inc; 🇺🇸 Indianapolis, Indiana, United States

Atlantic Melanoma Center; 🇺🇸 Morristown, New Jersey, United States

Ascension All Saints; 🇺🇸 Racine, Wisconsin, United States

Chilton Medical Center; 🇺🇸 Pompton Plains, New Jersey, United States

The Miriam Hospital; 🇺🇸 Providence, Rhode Island, United States

Brigham and Women's Hospital; 🇺🇸 Boston, Massachusetts, United States

University of Michigan; 🇺🇸 Ann Arbor, Michigan, United States

Ascension St. Francis Hospital; 🇺🇸 Milwaukee, Wisconsin, United States

Rhode Island Hospital; 🇺🇸 Providence, Rhode Island, United States