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

COVID-19 Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT04404361
• Other study ID #: PAC319
• Status: Terminated
• Phase: Phase 2
• Start date: May 22, 2020
• Est. completion date: September 21, 2021

Study information

• Verified date: May 2024
• Source: CTI BioPharma
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 200
• Est. completion date: September 21, 2021
• Est. primary completion date: September 21, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• COVID
• COVID-19
• COVID19

Intervention

Drug:
• Pacritinib
100 mg capsules
• Placebo
Placebo capsules matching pacritinib 100 mg capsules

Locations

Country	Name	City	State
United States	University of Michigan	Ann Arbor	Michigan
United States	Grady Memorial Hospital	Atlanta	Georgia
United States	St. Agnes Healthcare	Baltimore	Maryland
United States	Brigham and Women's Hospital	Boston	Massachusetts
United States	The Carl and Edyth Lindner Center for Research and Education at The Christ Hospital	Cincinnati	Ohio
United States	Ascension St. John Hospital	Detroit	Michigan
United States	St. Vincent Medical Group, Inc	Indianapolis	Indiana
United States	Ascension St. Vincent's Riverside Hospital	Jacksonville	Florida
United States	Ascension St. Francis Hospital	Milwaukee	Wisconsin
United States	Atlantic Melanoma Center	Morristown	New Jersey
United States	Overlook Medical Center	Morristown	New Jersey
United States	Mount Sinai Medical Center	New York	New York
United States	Ascension Providence Hospital - Novi Campus	Novi	Michigan
United States	St. Jude Hospital Yorba Linda dba St. Joseph Heritage Healthcare	Orange	California
United States	Albert Einstein Medical Center	Philadelphia	Pennsylvania
United States	Chilton Medical Center	Pompton Plains	New Jersey
United States	Rhode Island Hospital	Providence	Rhode Island
United States	The Miriam Hospital	Providence	Rhode Island
United States	Ascension All Saints	Racine	Wisconsin
United States	Providence Cancer Institute	Southfield	Michigan
United States	St. John Medical Center	Tulsa	Oklahoma

Sponsors (1)

Lead Sponsor	Collaborator
CTI BioPharma

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants With Progression to IMV and/or ECMO or Death	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).	Baseline to Day 28
Secondary	The Number of Ventilator-Free Days	the number of days that patients are alive and not intubated, from randomization to Day 28	Baseline to Day 28
Secondary	The Mortality Rate at Day 28	the number of patients with outcome of death during the 28 days following randomization	Baseline to Day 28
Secondary	The Mortality Rate at Day 15	the number of patients with outcome of death in the 15 days following randomization	Baseline to Day 15
Secondary	The Time to Improvement by at Least 2 Points Relative to Baseline on the 7-point Ordinal Scale of Clinical Status	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.	Baseline, Day 8, 15, 22, and 28.
Secondary	The Clinical Status as Assessed by the 7-point Ordinal Scale of Clinical Status at Days 8, 15, 22, and 28	Clinical status assessment based on the adapted scale from Cao et al. The patient CS is summarized by study visit.; STATUS: not hospitalized with resumption of normal activities; not hospitalized but unable to resume normal activities; hospitalization, not requiring supplemental oxygen; hospitalization, requiring supplemental oxygen not meeting the criteria for categories 5 or 6; hospitalization, on non-invasive positive pressure ventilation or high-flow nasal cannula; hospitalization, requiring IMV and/or ECMO; death.	Baseline, Day 8, 15, 22, 28
Secondary	The Rate of Use of Immunomodulatory Agents as Treatment for COVID-19	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	Baseline to Day 28