PRE-VENT Study in Hospitalized Patients With Severe COVID... | NCT04404361

Description Module

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.

Label	Type	Description	Intervention Names
Pacritinib and SOC	Experimental	Pacritinib 400 mg once daily [QD] on Day 1, then 200 mg twice daily [BID] from Day 2 to Day 14) + SOC	Drug: Pacritinib
Placebo and SOC	Placebo Comparator	4 capsules once daily [QD] on Day 1, then 2 capsules twice daily [BID] from Day 2 to Day 14) + SOC	Drug: Placebo

Name	Type	Description	Arm Group Labels	Other Names
Pacritinib	Drug	100 mg capsules	Pacritinib and SOC	SB1518

Measure	Description	Time Frame
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

Measure	Description	Time Frame
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
The Mortality Rate at Day 28	the number of patients with outcome of death during the 28 days following randomization

Eligibility Module

Eligibility Criteria

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

Facility	Status	City	State	ZIP	Country	Contacts
St. Jude Hospital Yorba Linda dba St. Joseph Heritage Healthcare		Orange	California	92868	United States

PubMed Identifier	Type	Citation	Retractions
36469321	Derived	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.

ID	Title	Description
FG000	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 Pacritinib: 100 mg capsules
FG001	Placebo and SOC

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Aug 11, 2021	Dec 29, 2023

ID	Title	Description
BG000	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 Pacritinib: 100 mg capsules
BG001	Placebo and SOC	4 capsules once daily [QD] on Day 1, then 2 capsules twice daily [BID] from Day 2 to Day 14) + SOC Placebo: Placebo capsules matching pacritinib 100 mg capsules
BG002	Total	Total of all reporting groups

Units	Counts
Participants	BG00099 BG001101 BG002200

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

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).

Posted

Count of Participants

Participants

Baseline to Day 28

ID	Title	Description
OG000	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 Pacritinib: 100 mg capsules
OG001	Placebo and SOC	4 capsules once daily [QD] on Day 1, then 2 capsules twice daily [BID] from Day 2 to Day 14) + SOC Placebo: Placebo capsules matching pacritinib 100 mg capsules

Units	Counts
Participants	OG00099 OG001101

Title

Denominators

Categories

Title	Measurements
	OG00026 OG00125

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001		Cochran-Mantel-Haenszel	Cochran-Mantel-Haenszel test stratified by age (<60 years versus ≥60 years) and 7-point clinical status scale (baseline 3 or 4 versus 5).	0.8516		Risk Difference (RD)	1.51			2-Sided	95	-10.55	13.53					Superiority

Secondary

The Number of Ventilator-Free Days

the number of days that patients are alive and not intubated, from randomization to Day 28

Posted

Mean

Standard Deviation

days

Baseline to Day 28

ID	Title	Description
OG000	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 Pacritinib: 100 mg capsules
OG001	Placebo and SOC	4 capsules once daily [QD] on Day 1, then 2 capsules twice daily [BID] from Day 2 to Day 14) + SOC Placebo: Placebo capsules matching pacritinib 100 mg capsules

Units	Counts
Participants	OG000

Secondary

The Mortality Rate at Day 28

the number of patients with outcome of death during the 28 days following randomization

Posted

Number

95% Confidence Interval

% of patients with outcome of death /D28

Baseline to Day 28

ID	Title	Description
OG000	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 Pacritinib: 100 mg capsules
OG001	Placebo and SOC	4 capsules once daily [QD] on Day 1, then 2 capsules twice daily [BID] from Day 2 to Day 14) + SOC Placebo: Placebo capsules matching pacritinib 100 mg capsules

Units	Counts
Participants	OG000

Secondary

The Mortality Rate at Day 15

the number of patients with outcome of death in the 15 days following randomization

Posted

Number

95% Confidence Interval

% of patients with outcome of death /D15

Baseline to Day 15

ID	Title	Description
OG000	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 Pacritinib: 100 mg capsules
OG001	Placebo and SOC	4 capsules once daily [QD] on Day 1, then 2 capsules twice daily [BID] from Day 2 to Day 14) + SOC Placebo: Placebo capsules matching pacritinib 100 mg capsules

Units	Counts
Participants	OG000

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.

Posted

Median

95% Confidence Interval

days

Baseline, Day 8, 15, 22, and 28.

ID	Title	Description
OG000	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 Pacritinib: 100 mg capsules
OG001	Placebo and SOC	4 capsules once daily [QD] on Day 1, then 2 capsules twice daily [BID] from Day 2 to Day 14) + SOC Placebo: Placebo capsules matching pacritinib 100 mg capsules

Units	Counts
Participants	OG000

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.

Posted

Number

participants

Baseline, Day 8, 15, 22, 28

ID	Title	Description
OG000	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 Pacritinib: 100 mg capsules
OG001	Placebo and SOC	4 capsules once daily [QD] on Day 1, then 2 capsules twice daily [BID] from Day 2 to Day 14) + SOC Placebo: Placebo capsules matching pacritinib 100 mg capsules

Units	Counts
Participants

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

Posted

Count of Participants

Participants

Baseline to Day 28

ID	Title	Description
OG000	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 Pacritinib: 100 mg capsules
OG001	Placebo and SOC	4 capsules once daily [QD] on Day 1, then 2 capsules twice daily [BID] from Day 2 to Day 14) + SOC Placebo: Placebo capsules matching pacritinib 100 mg capsules

Units	Counts
Participants	OG000

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
respiratory failure	Respiratory, thoracic and mediastinal disorders	MedDRA 23.1	Systematic Assessment	EG0007 events7 affected96 at risk EG00115 events15 affected101 at risk
acute respiratory failure	Respiratory, thoracic and mediastinal disorders	MedDRA 23.1	Systematic Assessment	EG0006 events6 affected96 at risk EG0018 events8 affected101 at risk
hypoxia	Respiratory, thoracic and mediastinal disorders	MedDRA 23.1	Systematic Assessment	EG0005 events4 affected96 at risk EG0018 events6 affected101 at risk
septic shock	Infections and infestations	MedDRA 23.1	Systematic Assessment	EG0002 events2 affected96 at risk EG0016 events6 affected101 at risk
acute kidney injury	Renal and urinary disorders	MedDRA 23.1	Systematic Assessment	EG0003 events3 affected96 at risk EG0013 events3 affected101 at risk
cardiac arrest	Cardiac disorders	MedDRA 23.1	Systematic Assessment	EG0001 events1 affected96 at risk EG0013 events3 affected101 at risk
acute respiratory distress syndrome	Respiratory, thoracic and mediastinal disorders	MedDRA 23.1	Systematic Assessment	EG0003 events3 affected96 at risk EG0010 events0 affected101 at risk
hypotension	Cardiac disorders	MedDRA 23.1	Systematic Assessment	EG0002 events2 affected96 at risk EG0011 events1 affected101 at risk
pulmonary embolism	Respiratory, thoracic and mediastinal disorders	MedDRA 23.1	Systematic Assessment	EG0000 events0 affected96 at risk EG0013 events3 affected101 at risk
cardio-respiratory arrest	Cardiac disorders	MedDRA 23.1	Systematic Assessment	EG0002 events2 affected96 at risk EG0010 events0 affected101 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Alanine aminotransferase increased	Hepatobiliary disorders	MedDRA 23.1	Systematic Assessment	EG00017 events15 affected96 at risk EG00119 events17 affected101 at risk
anaemia	Blood and lymphatic system disorders	MedDRA 23.1	Systematic Assessment	EG00012 events12 affected96 at risk EG00118 events18 affected101 at risk
bradycardia	Cardiac disorders	MedDRA 23.1	Systematic Assessment	EG00015 events15 affected96 at risk EG00111 events11 affected101 at risk
constipation	Gastrointestinal disorders	MedDRA 23.1	Systematic Assessment	EG00012 events12 affected96 at risk EG00113 events13 affected101 at risk
hypokalaemia	Metabolism and nutrition disorders	MedDRA 23.1	Systematic Assessment	EG00012 events12 affected96 at risk EG00117 events12 affected101 at risk
hyperkalaemia	Metabolism and nutrition disorders	MedDRA 23.1	Systematic Assessment	EG0009 events9 affected96 at risk EG00117 events11 affected101 at risk
acute kidney injury	Renal and urinary disorders	MedDRA 23.1	Systematic Assessment	EG00015 events9 affected96 at risk EG0017 events7 affected101 at risk
hypotension	Cardiac disorders	MedDRA 23.1	Systematic Assessment	EG0009 events8 affected96 at risk EG00113 events8 affected101 at risk
diarrhoea	Gastrointestinal disorders	MedDRA 23.1	Systematic Assessment	EG00012 events12 affected96 at risk EG0014 events4 affected101 at risk
Aspartate aminotransferase increased	Hepatobiliary disorders	MedDRA 23.1	Systematic Assessment	EG0009 events9 affected96 at risk EG0016 events6 affected101 at risk
hyperglycaemia	Metabolism and nutrition disorders	MedDRA 23.1	Systematic Assessment	EG0003 events3 affected96 at risk EG00111 events11 affected101 at risk
hypertension	Cardiac disorders	MedDRA 23.1	Systematic Assessment	EG0005 events5 affected96 at risk EG0018 events8 affected101 at risk
hypocalcaemia	Metabolism and nutrition disorders	MedDRA 23.1	Systematic Assessment	EG0008 events4 affected96 at risk EG00112 events8 affected101 at risk
insomnia	Nervous system disorders	MedDRA 23.1	Systematic Assessment	EG0006 events6 affected96 at risk EG0016 events6 affected101 at risk
atrial fibrillation	Cardiac disorders	MedDRA 23.1	Systematic Assessment	EG0005 events5 affected96 at risk EG0014 events4 affected101 at risk
Deep vein thrombosis	Vascular disorders	MedDRA 23.1	Systematic Assessment	EG0005 events5 affected96 at risk EG0014 events4 affected101 at risk
nausea	General disorders	MedDRA 23.1	Systematic Assessment	EG0004 events4 affected96 at risk EG0016 events6 affected101 at risk
anxiety	Psychiatric disorders	MedDRA 23.1	Systematic Assessment	EG0007 events6 affected96 at risk EG0013 events3 affected101 at risk
agitation	Psychiatric disorders	MedDRA 23.1	Systematic Assessment	EG0003 events3 affected96 at risk EG0015 events5 affected101 at risk
thrombocytopenia	Blood and lymphatic system disorders	MedDRA 23.1	Systematic Assessment	EG0003 events3 affected96 at risk EG0015 events5 affected101 at risk
encephalopathy	Nervous system disorders	MedDRA 23.1	Systematic Assessment	EG0001 events1 affected96 at risk EG0015 events5 affected101 at risk
epistaxis	General disorders	MedDRA 23.1	Systematic Assessment	EG0002 events2 affected96 at risk EG0015 events5 affected101 at risk
headache	Nervous system disorders	MedDRA 23.1	Systematic Assessment	EG0001 events1 affected96 at risk EG0015 events5 affected101 at risk

ID	Term
D011024	Pneumonia, Viral
D011014	Pneumonia
D012141	Respiratory Tract Infections
D007239	Infections
D014777	Virus Diseases
D018352	Coronavirus Infections
D003333	Coronaviridae Infections
D030341	Nidovirales Infections
D012327	RNA Virus Infections
D008171	Lung Diseases
D012140	Respiratory Tract Diseases

ID	Term
C561234	11-(2-pyrrolidin-1-ylethoxy)-14,19-dioxa-5,7,26-triazatetracyclo(19.3.1.1(2,6).1(8,12))heptacosa-1(25),2(26),3,5,8,10,12(27),16,21,23-decaene
D000075242	Janus Kinase Inhibitors

ID	Term
D047428	Protein Kinase Inhibitors
D004791	Enzyme Inhibitors
D045504	Molecular Mechanisms of Pharmacological Action
D020228	Pharmacologic Actions
D020164	Chemical Actions and Uses

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	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 Pacritinib: 100 mg capsules	12	96	20	96	74	96
EG001	Placebo and SOC	4 capsules once daily [QD] on Day 1, then 2 capsules twice daily [BID] from Day 2 to Day 14) + SOC Placebo: Placebo capsules matching pacritinib 100 mg capsules	12	101	33	101	79	101