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

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).

Completed
COVID-19
Coronavirus Infection

Drug: Piclidenoson

Piclidenoson 2 mg orally every 12 hours for up to 28 days
Other Name: CF101

Drug: Placebo

Placebo orally every 12 hours for up to 28 days

Eligibility Criteria

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)

Eligibility Gender
All
Eligibility Age
Minimum: 18 Years ~ Maximum: N/A
Countries
Bulgaria
Israel
Romania
Locations

II Multiprofile Hospital for Active Treatment - Sofia EAD
Sofia, Bulgaria

IV Multiprofile Hospital for Active Treatment - Sofia EAD
Sofia, Bulgaria

Hadassah Medical Center
Jerusalem, Israel

Shaare Zedek Medical Center
Jerusalem, Israel

Clinical Hospital for Infectious Diseases "St. Parascheva" Iasi
Iaşi, Romania

"Sfantul Ioan cel Nou" County Emergency Hospital Suceava
Suceava, Romania

Zivit Harpaz, Study Director
Can-Fite BioPharma Ltd

Rabin Medical Center
NCT Number
Keywords
Piclidenoson
CF101
SARS-CoV-2
MeSH Terms
COVID-19
Coronavirus Infections