COVID-19
Conditions
Interventions
Product Name: Piclidenoson
Product Code: CF101
Pharmaceutical Form: Tablet
INN or Proposed INN: Piclidenoson
CAS Number: 152918-18-8
Current Sponsor code: CF101
Other descriptive name: IB-MECA
Concent
Sponsors
Can-Fite BioPharma, Ltd.
Eligibility
Sex/Gender
All
Inclusion 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) 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 [hCG]) 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. a. For females: 2 of the following contraceptive methods, with at least 1 being a barrier method: - Hormonal contraceptives for = 27 days before dosing - Intrauterine device (IUD) in place = 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 = 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 [hCG]) within 24 hours prior to the start of investigational product. b. For males: Surgical sterilization (vasectomy = 1 month before screening) Or Both of the following contraceptive methods from screening: - Consistently and correctly use a condom - Partner must use a hormonal contraceptive or a nonhormonal barrier method (IUD or diaphragm with spermicide or cervical cap with spermicide). Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 40 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 20
Exclusion criteria
Exclusion criteria: 1. “Critical” Illness, per NIH COVID-19 Treatment Guidelines, including any of the following: Respiratory failure; or Septic shock; or Multiple organ dysfunction 2. Participation in another clinical trial concurrently 3. Subjects who require mechanical ventilation or extracorporeal membrane oxygenation (ECMO) 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 CredibleMedsTM list of drugs known to cause Torsades de Pointes (https://crediblemeds.org/) 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 Cockcroft-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)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the benefits of treatment with piclidenoson plus standard supportive care (SSC) (intervention arm) vs. placebo plus SSC (control arm) in hospitalized subjects with Moderate or Severe COVID-19. To evaluate the safety and tolerability of treatment with oral piclidenoson 2 mg every 12 hours (Q12H) in this population. ;Secondary Objective: None;Primary end point(s): Efficacy endpoints: • Proportion of subjects alive and free of respiratory failure (defined as need for non-invasive or invasive mechanical ventilation, high-flow oxygen, or ECMO) at Day 29 • Proportion of subjects alive and discharged to home without need for supplemental oxygen at Day 29 • 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 • Time (days) to improvement of 2 points on 8-point ordinal clinical scale • Incidence of mechanical ventilation • Ventilator-free days to Day 29 • Incidence of Intensive Care Unit (ICU) admission • Duration (days) of ICU stay • Time (days) to hospital discharge • Duration (days) of need for supplemental oxygen • SARS-CoV-2 viral load by quantitative RT-PCR • Time (days) to virus negativity by RT-PCR, defined as absence of SARS-CoV-2 on 2 consecutive days of sampling • Changes in serum cytokine levels Safety endpoints: • Incidence, nature, and severity of treatment-emergent and treatment-related severe adverse events (SAEs) • Incidence of AEs leading to early discontinuation of trial treatment • Incidence of treatment-emergent changes in clinical laboratory parameters (CBC, chemistry, coagulation, urinalysis) • Incidence of treatment-emergent changes in vital signs, ECGs, and physical examination results • Incidence of m | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): None;Timepoint(s) of evaluation of this end point: NA | — |
Countries
Bulgaria, Israel, Romania
Contacts
Public ContactDirector Clinical Operations
CanFite BioPharma Ltd.
Outcome results
None listed