Piclidenoson for Treatment of COVID-19

April 21, 2022 updated by: Can-Fite BioPharma

Piclidenoson for Treatment of COVID-19 - A Randomized, Double-Blind, Placebo-Controlled Trial

Patients with documented moderate COVID-19 infection will be randomized 1:1 to receive piclidenoson 2 mg Q12H orally with standard supportive care (SSC - intervention arm) or placebo orally with SSC (control arm) for up to 28 days.

Study Overview

Status

Completed

Intervention / Treatment

Detailed Description

This is a randomized, double-blind, placebo-controlled, pilot trial of piclidenoson 2 mg Q12H added to SSC, compared to placebo plus SSC, in a population of hospitalized subjects with "Moderate" or "Severe" COVID-19 per U.S. National Institutes of Health (NIH) Coronavirus Disease 2019 (COVID-19) Treatment Guidelines (2020). Subjects will be randomized according to a 1:1 ratio to one of the trial arms, and treated for up to 28 days, at the discretion of the Investigator. Piclidenoson 2 mg and placebo are supplied as matching tablets for oral administration.

Following initial diagnosis of COVID-19, and after having provided informed consent, subjects will be randomized according to 1:1 ratio to one of the trial arms on Day 0. SSC will be implemented and documented for all subjects, and maintained throughout the treatment period.

Vital signs (temperature, blood pressure, pulse rate per minute, respiratory rate per minute, oxygen saturation (SpO2), and PaO2/FiO2) of subjects will be monitored twice daily according to SSC. Parameters of clinical, respiratory, and vital status will be collected daily. Viral shedding will be assessed on a regular basis. Samples for pharmacokinetic (PK) analysis will be collected on Day 4.

Efficacy of piclidenoson will be assessed by clinical, respiratory, and virologic parameters. Safety and tolerability of piclidenoson will be assessed by adverse event (AE) monitoring, vital signs assessment, electrocardiograms (ECGs), and clinical laboratory tests (complete blood count (CBC) and extended chemistry panel). Adverse events will be graded by the Common Terminology Criteria for Adverse Events (CTCAE v5.0).

Study Type

Interventional

Enrollment (Actual)

6

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

      • Sofia, Bulgaria
        • II Multiprofile Hospital for Active Treatment - Sofia EAD
      • Sofia, Bulgaria
        • IV Multiprofile Hospital for Active Treatment - Sofia EAD
      • Jerusalem, Israel
        • Hadassah medical Center
      • Jerusalem, Israel
        • Shaare Zedek Medical Center
      • Iaşi, Romania
        • Clinical Hospital for Infectious Diseases "St. Parascheva" Iasi
      • Suceava, Romania
        • "Sfantul Ioan cel Nou" County Emergency Hospital Suceava

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

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. Hospitalized subjects 18 to 85 years of age, inclusive
  2. Able and willing to sign informed consent
  3. Molecular (RT-PCR) diagnosis of SARS-CoV-2 infection
  4. Moderate or Severe illness per NIH COVID-19 Treatment Guidelines:

    "Moderate" Illness:

    • Symptoms such as cough, fever, sore throat, malaise, myalgias, headache; and
    • Evidence of lower respiratory tract disease by clinical assessment and/or imaging; and
    • SpO2 >93% on room air at sea level

    "Severe" Illness, including any of the following:

    • Respiratory rate >30 breaths/minute; or
    • SpO2 ≤93% on room air at sea level; or
    • Ratio of arterial partial pressure of oxygen to fraction of inspired oxygen (PaO2/FiO2) <300; or
    • Lung infiltrates >50% of pulmonary volume on imaging
  5. Female subjects must have a negative serum pregnancy test (minimum sensitivity 25 IU/L or equivalent units of human chorionic gonadotropin) within 24 hours prior to the start of investigational product
  6. Female subjects of childbearing potential and male subjects with partners of childbearing potential must agree to use adequate methods of contraception during the study and through 90 days after the last dose of study medication. Female subjects of childbearing potential are all those except subjects who are surgically sterile, who have medically documented ovarian failure, or who are at least 1 year postmenopausal.

    1. For females: 2 of the following contraceptive methods, with at least 1 being a barrier method:

      • Hormonal contraceptives for at least 27 days before dosing
      • Intrauterine device (IUD) in place at least 27 days before dosing
      • Double-barrier methods (use of condom [male partner] with either diaphragm with spermicide or cervical cap with spermicide) from screening
      • Surgical sterilization of the partner (vasectomy at least 1 month before screening)
      • Female subjects must have a negative urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of human chorionic gonadotropin) within 24 hours prior to the start of investigational product.
    2. For males: Surgical sterilization (vasectomy at least 1 month before screening) or double barrier methods.

Exclusion Criteria

  1. 1. "Critical" Illness, per NIH COVID-19 Treatment Guidelines, including any of the following:

    • Respiratory failure; or
    • Septic shock; or
    • Multiple organ dysfunction
  2. Subjects who require mechanical ventilation or extracorporeal membrane oxygenation (ECMO)
  3. Participation in another clinical trial concurrently
  4. Concurrent treatment with immunomodulators or anti-rejection drugs
  5. Nursing women, pregnant women, women of childbearing potential who do not want adequate contraception
  6. History of any of the following diseases or conditions:

    • Advanced or decompensated liver disease (including presence or history of bleeding varices, ascites, encephalopathy, or hepato-renal syndrome)
    • Inability to swallow tablets, or gastrointestinal disease which could interfere with the absorption of piclidenoson
    • Any malignancy within 5 years before screening; exceptions are superficial dermatologic malignancies (e.g., squamous cell or basal cell skin cancer treated with curative intent)
    • Cardiomyopathy, significant ischemic cardiac or cerebrovascular disease (including history of angina, myocardial infarction, or interventional procedure for coronary artery disease), or cardiac rhythm disorder
    • QTcF interval on an average of triplicate ECGs >450 milliseconds (msec) for males or >470 msec for females (except when QT prolongation is associated with right or left bundle branch block, in which case enrollment is allowed)
    • Any condition which increases proarrhythmic risk, including hypokalemia, hypomagnesemia, congenital Long QT Syndrome
    • Ongoing or planned use of a concomitant medication that is on the CredibleMeds list of drugs known to cause Torsades de Pointes unless the subject can be screened and monitored under the guidelines proposed by Giudicessi (2020)
    • Pancreatitis
    • Severe or uncontrolled psychiatric disorder, e.g., depression, manic condition, psychosis, acute and/or chronic cognitive dysfunction, suicidal behavior, and relapse of substance abuse
    • Active seizure disorder defined by either an untreated seizure disorder or continued seizure activity within the preceding year despite treatment with anti-seizure medication
    • Bone marrow or solid organ transplantation
    • Any serious condition that, in the opinion of the investigator, would preclude evaluation of response or make it unlikely that the contemplated course of therapy and follow-up could be completed
  7. Any of the following abnormal laboratory tests:

    • Platelet count <90,000 cells/mm3
    • Absolute neutrophil count (ANC) <1,500 cells/mm3
    • Estimated creatinine clearance (CrCl) <50 mL/min by Cockroft-Gault formulation
    • Bilirubin level ≥2.5 mg/dL unless due to Gilbert's syndrome
    • AST or ALT level ≥3X the upper limit of normal
    • Serum albumin level <3.0 g/dL
    • International normalized ratio (INR) ≥1.5 (except subjects maintained on anticoagulant medications)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: QUADRUPLE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: Piclidenoson
Piclidenoson 2 mg every 12 hours orally added to standard of care
Piclidenoson 2 mg orally every 12 hours for up to 28 days
Other Names:
  • CF101
PLACEBO_COMPARATOR: Placebo
Placebo every 12 hours orally added to standard of care
Placebo orally every 12 hours for up to 28 days

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Proportion of subjects alive and free of respiratory failure
Time Frame: 29 days
Proportion of subjects alive and free of respiratory failure (defined as need for non-invasive or invasive mechanical ventilation, high-flow oxygen, or extracorporeal membrane oxygenation) at Day 29
29 days
Proportion of subjects discharged home alive
Time Frame: 29 days
Proportion of subjects alive and discharged to home without need for supplemental oxygen at Day 29
29 days
Treatment-emergent adverse events (AEs)
Time Frame: 29 days
Proportion of patients experiencing AEs
29 days

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Clinical status
Time Frame: 29 days

• Clinical status at Day 29 on NIAID 8-point ordinal scale (NIH 2020):

  1. Not hospitalized, no limitations
  2. Not hospitalized, with limitations
  3. Hospitalized, no active medical problems
  4. Hospitalized, not on oxygen
  5. Hospitalized, on oxygen
  6. Hospitalized, on high-flow oxygen or noninvasive mechanical ventilation
  7. Hospitalized, on mechanical ventilation or ECMO
  8. Death
29 days
Time to improvement
Time Frame: 29 days
Time (days) to improvement of 2 points on 7-point ordinal clinical scale
29 days
Incidence of mechanical ventilation
Time Frame: 29 days
Proportion of patients who require mechanical ventilation
29 days
Ventilator-free days
Time Frame: 29 days
Ventilator-free days to Day 29
29 days
Incidence of Intensive Care Unit (ICU) admission
Time Frame: 29 days
Proportion of patients who require ICU admission
29 days
Duration of ICU stay
Time Frame: 29 days
Duration (days) of ICU stay
29 days
Time to hospital discharge
Time Frame: 29 days
Time (days) to hospital discharge
29 days
Duration of need for supplemental oxygen
Time Frame: 29 days
Duration (days) of need for supplemental oxygen
29 days
Time to virus negativity
Time Frame: 29 days
Time (days) to virus negativity by RT-PCR, defined as absence of SARS CoV 2 on 2 consecutive days of sampling
29 days
SARS-CoV-2 viral load
Time Frame: 29 days
SARS-CoV-2 viral load (number of copies) by quantitative RT-PCR
29 days
AEs leading to withdrawal
Time Frame: 29 days
Proportion of patients experiencing AEs leading to early discontinuation of trial treatment
29 days
Treatment-emergent serious AEs (SAEs)
Time Frame: 29 days
Proportion of patients experiencing SAEs
29 days
Treatment-emergent abnormalities in clinical laboratory parameters or electrocardiograms (ECGs)
Time Frame: 29 days
Proportion of patients experiencing treatment-emergent changes in clinical laboratory parameters or ECGs
29 days
Incidence of meeting safety-related stopping rules
Time Frame: 29 days
Proportion of patients who meet study safety-related stopping rules
29 days
Pharmacokinetics of piclidenoson in this patient population
Time Frame: 5 days
Plasma concentrations over time of piclidenoson
5 days
Serum cytokine levels
Time Frame: 29 days
Change from baseline in serum concentrations of cytokines
29 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Collaborators

Investigators

  • Study Director: Zivit Harpaz, Can-Fite BioPharma Ltd

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

January 6, 2021

Primary Completion (ACTUAL)

March 6, 2022

Study Completion (ACTUAL)

April 21, 2022

Study Registration Dates

First Submitted

April 1, 2020

First Submitted That Met QC Criteria

April 2, 2020

First Posted (ACTUAL)

April 3, 2020

Study Record Updates

Last Update Posted (ACTUAL)

April 22, 2022

Last Update Submitted That Met QC Criteria

April 21, 2022

Last Verified

March 1, 2022

More Information

Terms related to this study

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

To be determined

IPD Sharing Time Frame

January 2021, indefinitely

IPD Sharing Access Criteria

To be determined

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • CSR

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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