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

NCT ID: NCT04404361

Last Updated: 2024-06-05

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 200 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-05-22
• Study Completion Date: 2021-09-21

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.

Conditions

COVID19; COVID-19; COVID

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Pacritinib and SOC

Pacritinib 400 mg once daily \[QD\] on Day 1, then 200 mg twice daily \[BID\] from Day 2 to Day 14) + SOC

Group Type: EXPERIMENTAL

Pacritinib

Intervention Type: DRUG

100 mg capsules

Placebo and SOC

4 capsules once daily \[QD\] on Day 1, then 2 capsules twice daily \[BID\] from Day 2 to Day 14) + SOC

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Placebo capsules matching pacritinib 100 mg capsules

Interventions

Pacritinib

100 mg capsules

Intervention Type: DRUG

Placebo

Placebo capsules matching pacritinib 100 mg capsules

Intervention Type: DRUG

Other Intervention Names

SB1518; Oral Jak Inhibitor; Oral Irak inhibitor; Oral Csf1 inhibitor

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

CTI BioPharma

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

St. Jude Hospital Yorba Linda dba St. Joseph Heritage Healthcare

Orange, California, United States

Ascension St. Vincent's Riverside Hospital

Jacksonville, Florida, United States

Grady Memorial Hospital

Atlanta, Georgia, United States

St. Vincent Medical Group, Inc

Indianapolis, Indiana, United States

St. Agnes Healthcare

Baltimore, Maryland, United States

Brigham and Women's Hospital

Boston, Massachusetts, United States

University of Michigan

Ann Arbor, Michigan, United States

Ascension St. John Hospital

Detroit, Michigan, United States

Ascension Providence Hospital - Novi Campus

Novi, Michigan, United States

Providence Cancer Institute

Southfield, Michigan, United States

Atlantic Melanoma Center

Morristown, New Jersey, United States

Overlook Medical Center

Morristown, New Jersey, United States

Chilton Medical Center

Pompton Plains, New Jersey, United States

Mount Sinai Medical Center

New York, New York, 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

Albert Einstein Medical Center

Philadelphia, Pennsylvania, United States

Rhode Island Hospital

Providence, Rhode Island, United States

The Miriam Hospital

Providence, Rhode Island, United States

Ascension St. Francis Hospital

Milwaukee, Wisconsin, United States

Ascension All Saints

Racine, Wisconsin, United States

Countries

United States

References

Cafardi J, Miller C, Terebelo H, Tewell C, Benzaquen S, Park D, Egan P, Lebovic D, Pettit K, Whitman E, Tremblay D, Feld J, Buckley S, Roman-Torres K, Smith J, Craig A, Mascarenhas J. Efficacy and Safety of Pacritinib vs Placebo for Patients With Severe COVID-19: A Phase 2 Randomized Clinical Trial. JAMA Netw Open. 2022 Dec 1;5(12):e2242918. doi: 10.1001/jamanetworkopen.2022.42918.

Reference Type: DERIVED

PMID: 36469321 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

PAC319

Identifier Type: -

Identifier Source: org_study_id