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

Trial Profile

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

Status: Recruiting
Phase of Trial: Phase II

Latest Information Update: 15 Jul 2020

At a glance

  • Drugs Piclidenoson (Primary)
  • Indications COVID 2019 infections; Respiratory insufficiency
  • Focus Adverse reactions; Expanded access; Therapeutic Use
  • Sponsors Can-Fite BioPharma
  • Most Recent Events

    • 04 Jul 2020 Outcome measures amended. Time frame changed from 28 days to 29 days. Arms amended. Study design changed from open label to double blind. Eligibility criteria amended.
    • 04 Jul 2020 Planned End Date changed from 6 Jun 2020 to 6 Jul 2021.
    • 04 Jul 2020 Planned primary completion date changed from 6 Jun 2020 to 6 Mar 2021.

Trial Overview

Purpose

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.

Primary Endpoints

Proportion of subjects alive and free of respiratory failure

description: 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
time_frame: 29 days

Proportion of subjects discharged home alive

description: Proportion of subjects alive and discharged to home without need for supplemental oxygen at Day 29
time_frame: 29 days

Treatment-emergent adverse events (AEs)

description: Proportion of patients experiencing AEs
time_frame: 29 days

Other Endpoints

Clinical status

description: Clinical status at Day 29 on a 7-point ordinal scale, where 1 = not hospitalized with resumption of normal activities; 2 = not hospitalized but unable to resume normal activities; 3 = hospitalized but not requiring supplemental oxygen; 4 = hospitalized and requiring supplemental oxygen; 5 = hospitalized and requiring nasal high-flow oxygen therapy and/or noninvasive mechanical ventilation; 6 = hospitalized and requiring invasive mechanical ventilation and/or extra-corporeal membrane oxygenation; and 7 = death
time_frame: 29 days

Time to improvement

description: Time (days) to improvement of 2 points on 7-point ordinal clinical scale
time_frame: 29 days

Incidence of mechanical ventilation

description: Proportion of patients who require mechanical ventilation
time_frame: 29 days

Ventilator-free days

description: Ventilator-free days to Day 29
time_frame: 29 days

Incidence of Intensive Care Unit (ICU) admission

description: Proportion of patients who require ICU admission
time_frame: 29 days

Duration of ICU stay

description: Duration (days) of ICU stay
time_frame: 29 days

Time to hospital discharge

description: Time (days) to hospital discharge
time_frame: 29 days

Duration of need for supplemental oxygen

description: Duration (days) of need for supplemental oxygen
time_frame: 29 days

Time to virus negativity

description: Time (days) to virus negativity by RT-PCR, defined as absence of SARS CoV 2 on 2 consecutive days of sampling
time_frame: 29 days

SARS-CoV-2 viral load

description: SARS-CoV-2 viral load (number of copies) by quantitative RT-PCR
time_frame: 29 days

AEs leading to withdrawal

description: Proportion of patients experiencing AEs leading to early discontinuation of trial treatment
time_frame: 29 days

Treatment-emergent serious AEs (SAEs)

description: Proportion of patients experiencing SAEs
time_frame: 29 days

Treatment-emergent abnormalities in clinical laboratory parameters or electrocardiograms (ECGs)

description: Proportion of patients experiencing treatment-emergent changes in clinical laboratory parameters or ECGs
time_frame: 29 days

Incidence of meeting safety-related stopping rules

description: Proportion of patients who meet study safety-related stopping rules
time_frame: 29 days

Pharmacokinetics of piclidenoson in this patient population

description: Plasma concentrations over time of piclidenoson
time_frame: 5 days [1]

Diseases Treated

Indication Qualifiers Patient Segments
COVID 2019 infections treatment -
Respiratory insufficiency treatment -

Subjects

  • Subject Type patients
  • Number

    Planned: 40

  • Sex male & female
  • Age Group ≥ 18 years; adult

Patient Inclusion Criteria

Inclusion Criteria 1. ≥18 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 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 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.

Patient 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) - Immunologically mediated disease (e.g., rheumatoid arthritis, inflammatory bowel disease, severe psoriasis, systemic lupus erythematosus) that requires more than intermittent nonsteroidal anti-inflammatory medications for management or that requires use of systemic corticosteroids in the 1 month before screening (inhaled asthma medications are allowed) - 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)

Trial Details

Identifiers

Identifier Owner
NCT04333472 ClinicalTrials.gov: US National Institutes of Health
CF101-241COVID19 -

Organisations

  • Sponsors Can-Fite BioPharma
  • Affiliations Can-Fite BioPharma

Trial Dates

  • Initiation Dates

    Planned : 06 Sep 2020

  • Primary Completion Dates

    Planned : 06 Mar 2021

  • End Dates

    Planned : 06 Jul 2021

Other Details

  • Design double-blind; parallel; prospective; randomised
  • Phase of Trial Phase II
  • Location Israel
  • Focus Adverse reactions; Expanded access; Therapeutic Use

Interventions

Drugs Route Formulation
PiclidenosonPrimary Drug Oral Tablet

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

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

Trial Centres

Investigators

Investigator Centre Name Trial Centre Country
Zivit Harpaz
+972-3-9241114
Zivit@canfite.co.il
show details
Can-Fite BioPharma Ltd
-

Centres

Centre Name Location Trial Centre Country
Can-Fite BioPharma
-
-
Can-Fite BioPharma Ltd
-
-
Rabin Medical Center
-
-
Rabin Medical Center Petah tikva Israel

Trial History

Event Date Event Type Comment
15 Jul 2020 Other trial event Last checked against ClinicalTrials.gov record. Updated 15 Jul 2020
04 Jul 2020 Protocol amendment Outcome measures amended. Time frame changed from 28 days to 29 days. Arms amended. Study design changed from open label to double blind. Eligibility criteria amended. Updated 08 Jul 2020
04 Jul 2020 Completion date Planned End Date changed from 6 Jun 2020 to 6 Jul 2021. Updated 08 Jul 2020
04 Jul 2020 Other trial event Planned primary completion date changed from 6 Jun 2020 to 6 Mar 2021. Updated 08 Jul 2020
01 Jun 2020 Status change - recruiting Status changed from not yet recruiting to recruiting, according to a Can-Fite Biopharma media release. Updated 04 Jun 2020
01 Jun 2020 Other trial event According to a Can-Fite Biopharma media release, company commenced the trial, it has not enrolled patients due to the decreased number of COVID-19 cases in Israel. Updated 04 Jun 2020
13 Apr 2020 Other trial event According to a Can-Fite Biopharma media release, the company has received approval from the Institutional Review Board (IRB) at Rabin Medical Center to initiate this pilot clinical study. Patient enrollment and dosing will begin immediately. Updated 15 Apr 2020
07 Apr 2020 Other trial event New source identified and integrated: (ClinicalTrials.gov: US National Institutes of Health: NCT04333472). Updated 07 Apr 2020
06 Apr 2020 Status change - not yet recruiting Status changed from planning to not yet recruiting. Updated 07 Apr 2020
31 Mar 2020 New trial record New trial record Updated 31 Mar 2020
23 Mar 2020 Other trial event According to a Can-Fite Biopharma media release, the company has submitted Piclidenoson for a compassionate use program to treat coronavirus patients to the Institutional Review Board at Rabin Medical Center. If approved, the compassionate use program will be led by Dr. Dror Diker, M.D., Head of Internal Medicine D at the Rabin Medical Center. Patients would be treated at Rabins Golda Hasharon Campus which is currently positioned to treat coronavirus patients in a specialized setting. Updated 31 Mar 2020

References

  1. ClinicalTrials.gov: US National Institutes of Health. Trial-Reg 2016;.

    Available from: URL: http://clinicaltrials.gov
  2. Can-Fite BioPharma. Can-Fite: Piclidenoson is Submitted for Compassionate Use Treatment for Coronavirus Patients in Israel. Media-Rel 2020;.

    Media Release
  3. Can-Fite BioPharma. Can Fite Received Approval for COVID-19 Clinical Trial in Israel, Patient Enrollment and Dosing to Commence Immediately. Media-Rel 2020;.

    Media Release
  4. Can-Fite BioPharma. Can-Fite Reports First Quarter 2020 Financial Results & Provides Clinical Update. Media-Rel 2020;.

    Media Release
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