Efficacy of PJS-539 for Adult Patients With COVID-19. (PJS-539)

Efficacy of PJS-539 for Adult Patients With SARS-CoV-2: Multicentre, Phase 2, Randomized, Double-blind, Placebo-controlled Clinical Trial.

The PJS-539 is a multicentre, phase 2, randomized, double-blind, placebo-controlled clinical trial to evaluate the effect of PJS-539 in the viral load of patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).

Study Overview

• Status: Completed
• Conditions: Covid19; COVID-19 Pneumonia
• Intervention / Treatment: Drug: Placebo; Drug: PJS-539 Dose 1; Drug: PJS-539 Dose 2

Detailed Description

COVID-19, a disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) became a pandemic in March 2020. Clinically, the coronavirus disease 2019 (COVID-19) ranges from asymptomatic disease in some to severe forms. However, until now, only the use of corticosteroids in selected patients has been shown to improve clinical outcomes in patients with COVID-19.

PJS-539 has been demonstrated to inhibit viral uptake and replication of SARS-CoV-2.

The objective of this Phase II trial is to assess the effect of PJS-539 in the viral load of patients with mild to moderate COVID-19 symptoms.

• Study Type: Interventional
• Enrollment (Actual): 153
• Phase: Phase 2

Contacts and Locations

Study Locations

• Brazil
  • SP
    • Sao Paulo, SP, Brazil, 04005-000
      • Hospital do Coracao

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Adult patients (age ≥ 18 years);

2. COVID-19 diagnosis confirmed by:

   1. Detection of SARS-CoV-2 by reverse transcription polymerase chain reaction (RT-PCR), or
   2. Rapid genetic or antigen tests validated by Brazilian National Health Surveillance Agency (ANVISA);
3. Mild or moderate symptoms without indication for hospitalization;
4. Symptoms started seven days ago or less;
5. Be able to access the study's online questionnaire.

Exclusion Criteria:

1. Pregnant or lactating women;
2. Known allergy or hypersensitivity to the study drug;

3. Patients at high risk of bleeding, defined by:

   1. Previous Intracranial hemorrhage,
   2. Ischemic stroke in the last 3 months,
   3. Anatomical vascular alteration of the central nervous system known, such as aneurysms or arteriovenous malformations,
   4. Malignant neoplasm of the central nervous system known,
   5. Metastatic solid neoplasia,
   6. Significant closed head or facial trauma in the last 3 months (defined as any trauma that required medical evaluation or hospitalization),
   7. Known intracranial abnormalities not listed as absolute contraindications (e.g., benign intracranial tumor),
   8. Bleeding in the last 2 to 4 weeks (excluding menstrual bleeding),
   9. Surgical procedure in the last 3 weeks,
   10. Current use of full-dose anticoagulants (warfarin, enoxaparin or new anticoagulants) or dual antiplatelet therapy,
   11. Thrombocytopenia (<100,000/mL) or international normalized ratio (INR) > 1.3;
4. Renal failure, defined as glomerular filtration rate (GFR) estimated by the formulas Modification of Diet in Renal Disease (MDRD) or Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) <30 mL/min/1.73m2;
5. Previous participation in the study;
6. History of liver disease (cirrhosis) reported by the patient or in medical records, presence of esophageal varices or presence of ascites;
7. Decompensated heart failure, defined by the presence of dyspnea attributed to cardiac cause, edema of the lower limbs, crackles on pulmonary auscultation or pathological jugular turgency.
8. Participation in other clinical trials with antivirals in COVID-19

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Patients will receive placebo orally once daily for 10 days.	Drug: Placebo; Patients will receive placebo daily for 10 days.
Experimental: PJS-539 Dose 1; Patients will receive PJS-539 dose 1 orally once daily for 10 days.	Drug: PJS-539 Dose 1; Patients will receive PJS-539 dose 1 daily for 10 days.
Experimental: PJS-539 Dose 2; Patients will receive PJS-539 dose 2 orally once daily for 10 days.	Drug: PJS-539 Dose 2; Patients will receive PJS-539 Dose 2 daily for 10 days.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Decay rate of the SARS-CoV-2 viral load.	Decay rate of the SARS-CoV-2 viral load logarithmic curve obtained via nasopharyngeal swab between the baseline and the fifth and tenth days after randomization.	At day 10

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hospital admission	Need for hospital admission.	Day 28
Need for invasive mechanical ventilation	Intubation and initiation of mechanical ventilation for any given reason	Day 28
Time to symptoms resolution	Time from randomization to symptoms resolution	Day 10
Ordinal clinical scale of symptoms	Evaluation of the clinical scale of symptoms, which ranges from 1 to 7 as follows: 1. not hospitalized, without limitation of daily activities; 2. not hospitalized, with limitation of daily activities; 3. hospitalized, without the need for supplemental oxygen; 4. hospitalized, requiring supplemental oxygen; 5 hospitalized, requiring high-flow nasal oxygen therapy, non-invasive mechanical ventilation, or both; 6. hospitalized, requiring blood oxygenation through a membrane system, invasive mechanical ventilation, or both; 7. Death.	Day 14
Adverse events	Grade 1, 2, 3 and 4 adverse events, which were not present at the patient's entrance, defined by the Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events	Up to 28 days
Bleeding	Defines as: Major: Defined as clinical bleeding associated with any of the following: fatal outcome, critical site involvement (intracranial, intraspinal, intraocular, pericardial, intra-articular, intramuscular with compartmental or retroperitoneal syndrome), or clinical bleeding with a drop in hemoglobin concentration ≥2g/dL, or need for transfusion of ≥2 units of packed red blood cells or whole blood. All intracerebral (or intraparenchymal) bleeds are included in the primary analysis as hemorrhagic stroke. Clinically relevant non-major: Defined as clinical bleeding that does not present major bleeding criteria, but requires medical intervention, unscheduled contact (in person or by telephone) with a doctor, temporary interruption of the study drug, pain or impairment of daily activities. Minor: Defined as clinical bleeding that does not meet criteria for clinically relevant major or non-major bleeding.	Up to 28 days

Collaborators and Investigators

• Sponsor: Hospital do Coracao
• Collaborators: Covicept
• Investigators: Principal Investigator: Bruno Tomazini, MD, Hospital do Coracao; Study Director: Alexandre Biasi Cavalcanti, MD, PhD, Hospital do Coracao

Study record dates

Study Major Dates

• Study Start (Actual): September 25, 2021
• Primary Completion (Actual): February 3, 2022
• Study Completion (Actual): March 4, 2022

Study Registration Dates

• First Submitted: August 16, 2021
• First Submitted That Met QC Criteria: August 16, 2021
• First Posted (Actual): August 17, 2021

Study Record Updates

• Last Update Posted (Actual): April 12, 2022
• Last Update Submitted That Met QC Criteria: April 11, 2022
• Last Verified: February 1, 2022

More Information

Terms related to this study

• Keywords: COVID-19; Antiviral
• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19
• Other Study ID Numbers: IP-HCOR/PJS-539; Phase2_PJS-539 (Other Identifier: IP-HCor)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No