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Piclidenoson for Treatment of COVID-19

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04333472
Recruitment Status : Not yet recruiting
First Posted : April 3, 2020
Last Update Posted : September 29, 2020
Sponsor:
Collaborator:
Rabin Medical Center
Information provided by (Responsible Party):
Can-Fite BioPharma

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
COVID-19 Coronavirus Infection Drug: Piclidenoson Drug: Placebo Phase 2

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" 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).

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 40 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Piclidenoson for Treatment of COVID-19 - A Randomized, Double-Blind, Placebo-Controlled Trial
Estimated Study Start Date : October 6, 2020
Estimated Primary Completion Date : March 6, 2021
Estimated Study Completion Date : July 6, 2021

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Piclidenoson
Piclidenoson 2 mg every 12 hours orally added to standard of care
Drug: Piclidenoson
Piclidenoson 2 mg orally every 12 hours for up to 28 days
Other Name: CF101

Placebo Comparator: Placebo
Placebo every 12 hours orally added to standard of care
Drug: Placebo
Placebo orally every 12 hours for up to 28 days




Primary Outcome Measures :
  1. 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

  2. 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

  3. Treatment-emergent adverse events (AEs) [ Time Frame: 29 days ]
    Proportion of patients experiencing AEs


Secondary Outcome Measures :
  1. 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

  2. Time to improvement [ Time Frame: 29 days ]
    Time (days) to improvement of 2 points on 7-point ordinal clinical scale

  3. Incidence of mechanical ventilation [ Time Frame: 29 days ]
    Proportion of patients who require mechanical ventilation

  4. Ventilator-free days [ Time Frame: 29 days ]
    Ventilator-free days to Day 29

  5. Incidence of Intensive Care Unit (ICU) admission [ Time Frame: 29 days ]
    Proportion of patients who require ICU admission

  6. Duration of ICU stay [ Time Frame: 29 days ]
    Duration (days) of ICU stay

  7. Time to hospital discharge [ Time Frame: 29 days ]
    Time (days) to hospital discharge

  8. Duration of need for supplemental oxygen [ Time Frame: 29 days ]
    Duration (days) of need for supplemental oxygen

  9. 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

  10. SARS-CoV-2 viral load [ Time Frame: 29 days ]
    SARS-CoV-2 viral load (number of copies) by quantitative RT-PCR

  11. AEs leading to withdrawal [ Time Frame: 29 days ]
    Proportion of patients experiencing AEs leading to early discontinuation of trial treatment

  12. Treatment-emergent serious AEs (SAEs) [ Time Frame: 29 days ]
    Proportion of patients experiencing SAEs

  13. 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

  14. Incidence of meeting safety-related stopping rules [ Time Frame: 29 days ]
    Proportion of patients who meet study safety-related stopping rules

  15. Pharmacokinetics of piclidenoson in this patient population [ Time Frame: 5 days ]
    Plasma concentrations over time of piclidenoson

  16. Serum cytokine levels [ Time Frame: 29 days ]
    Change from baseline in serum concentrations of cytokines



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria

  1. 18-85 years of age
  2. Able and willing to sign informed consent
  3. Molecular (RT-PCR) diagnosis of SARS-CoV-2 infection
  4. Moderate illness per NIH COVID-19 Treatment Guidelines:

    • 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
  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. 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
  2. Critical illness, including any of the following:

    • Respiratory failure; or
    • Septic shock; or
    • Multiple organ dysfunction
  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)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04333472


Contacts
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Contact: Zivit Harpaz +972-3-9241114 Zivit@canfite.co.il

Locations
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Israel
Shaare Zedek Medical Center
Jerusalem, Israel
Contact: Ramzi Kurd, MD    +972-52-2362671    ramzik@szmc.org.il   
Rabin Medical Center
Petah tikva, Israel
Contact: Yoseph Caraco, MD    +972-2-6778584    caraco@hadassah.org.il   
Sponsors and Collaborators
Can-Fite BioPharma
Rabin Medical Center
Investigators
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Study Director: Zivit Harpaz Can-Fite BioPharma Ltd
Additional Information:
Publications:
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Responsible Party: Can-Fite BioPharma
ClinicalTrials.gov Identifier: NCT04333472    
Other Study ID Numbers: CF101-241COVID-19
First Posted: April 3, 2020    Key Record Dates
Last Update Posted: September 29, 2020
Last Verified: September 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: To be determined
Supporting Materials: Study Protocol
Clinical Study Report (CSR)
Time Frame: January 2021, indefinitely
Access Criteria: To be determined

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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
Keywords provided by Can-Fite BioPharma:
Piclidenoson
CF101
SARS-CoV-2
Additional relevant MeSH terms:
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Coronavirus Infections
Severe Acute Respiratory Syndrome
Coronaviridae Infections
Nidovirales Infections
RNA Virus Infections
Virus Diseases
Respiratory Tract Infections
Respiratory Tract Diseases