COVID-19Phase 2NCT04333472
Piclidenoson for Treatment of COVID-19
A Phase 2 study testing Piclidenoson in people with COVID-19 and Coronavirus Infection, run by Can-Fite BioPharma at 6 sites in 3 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- COVID-19, Coronavirus Infection
- What is being tested?
- Piclidenoson
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 6 participants
- Where
- 6 sitesin 3 countries
- Study dates
- 6 Jan 2021to 21 Apr 2022
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Hospitalized subjects 18 to 85 years of age, inclusive
- Able and willing to sign informed consent
- Molecular (RT-PCR) diagnosis of SARS-CoV-2 infection
- Moderate or Severe illness per NIH COVID-19 Treatment Guidelines:
- "Moderate" Illness:
- Symptoms such as cough, fever, sore throat, malaise, myalgias, headache; and
Show all 22Show fewer
- 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
- 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
- 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.
- 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.
- For males: Surgical sterilization (vasectomy at least 1 month before screening) or double barrier methods.
Who cannot join
- 1. "Critical" Illness, per NIH COVID-19 Treatment Guidelines, including any of the following:
- Respiratory failure; or
- Septic shock; or
- Multiple organ dysfunction
- Subjects who require mechanical ventilation or extracorporeal membrane oxygenation (ECMO)
- Participation in another clinical trial concurrently
Show all 29Show fewer
- Concurrent treatment with immunomodulators or anti-rejection drugs
- Nursing women, pregnant women, women of childbearing potential who do not want adequate contraception
- 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
- 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 locations and contacts
6 sites in 3 countries.
6 sites in 3 countries
Bulgaria2 sites
II Multiprofile Hospital for Active Treatment - Sofia EAD
Sofia
IV Multiprofile Hospital for Active Treatment - Sofia EAD
Sofia
Israel2 sites
Hadassah Medical Center
Jerusalem
Shaare Zedek Medical Center
Jerusalem
Romania2 sites
Clinical Hospital for Infectious Diseases "St. Parascheva" Iasi
Iași
"Sfantul Ioan cel Nou" County Emergency Hospital Suceava
Suceava
About this study
Official title: 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.
Read the 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).
- Conditions
- COVID-19, Coronavirus Infection
- Being tested
- Piclidenoson, Placebo
- Keywords
- Piclidenoson, CF101, SARS-CoV-2
- Medical subject headings
- COVID-19, Coronavirus Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PiclidenosonDrug
Also called CF101
Piclidenoson 2 mg orally every 12 hours for up to 28 days
PlaceboDrug
Placebo orally every 12 hours for up to 28 days
| Study group | Role | What they receive |
|---|---|---|
| Piclidenoson | Experimental | Piclidenoson 2 mg every 12 hours orally added to standard of care Receives: Drug: Piclidenoson |
| Placebo | Placebo comparator | Placebo every 12 hours orally added to standard of care Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Proportion of subjects alive and free of respiratory failure
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
Measured: 29 days
Proportion of subjects discharged home alive
Proportion of subjects alive and discharged to home without need for supplemental oxygen at Day 29
Measured: 29 days
Treatment-emergent adverse events (AEs)
Proportion of patients experiencing AEs
Measured: 29 days
Secondary outcomes (16)
Clinical status
- Clinical status at Day 29 on NIAID 8-point ordinal scale (NIH 2020):
- Not hospitalized, no limitations
- Not hospitalized, with limitations
- Hospitalized, no active medical problems
- Hospitalized, not on oxygen
- Hospitalized, on oxygen
- Hospitalized, on high-flow oxygen or noninvasive mechanical ventilation
- Hospitalized, on mechanical ventilation or ECMO
- Death
Measured: 29 days
Time to improvement
Time (days) to improvement of 2 points on 7-point ordinal clinical scale
Measured: 29 days
Incidence of mechanical ventilation
Proportion of patients who require mechanical ventilation
Measured: 29 days
Ventilator-free days
Ventilator-free days to Day 29
Measured: 29 days
Incidence of Intensive Care Unit (ICU) admission
Proportion of patients who require ICU admission
Measured: 29 days
Duration of ICU stay
Duration (days) of ICU stay
Measured: 29 days
Time to hospital discharge
Time (days) to hospital discharge
Measured: 29 days
Duration of need for supplemental oxygen
Duration (days) of need for supplemental oxygen
Measured: 29 days
Time to virus negativity
Time (days) to virus negativity by RT-PCR, defined as absence of SARS CoV 2 on 2 consecutive days of sampling
Measured: 29 days
SARS-CoV-2 viral load
SARS-CoV-2 viral load (number of copies) by quantitative RT-PCR
Measured: 29 days
AEs leading to withdrawal
Proportion of patients experiencing AEs leading to early discontinuation of trial treatment
Measured: 29 days
Treatment-emergent serious AEs (SAEs)
Proportion of patients experiencing SAEs
Measured: 29 days
Treatment-emergent abnormalities in clinical laboratory parameters or electrocardiograms (ECGs)
Proportion of patients experiencing treatment-emergent changes in clinical laboratory parameters or ECGs
Measured: 29 days
Incidence of meeting safety-related stopping rules
Proportion of patients who meet study safety-related stopping rules
Measured: 29 days
Pharmacokinetics of piclidenoson in this patient population
Plasma concentrations over time of piclidenoson
Measured: 5 days
Serum cytokine levels
Change from baseline in serum concentrations of cytokines
Measured: 29 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Apr 2020
- Study start6 Jan 2021
- Primary completion6 Mar 2022
- Study completion21 Apr 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for COVID-19Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 6 participants (actual)
Sponsor and investigators
- Lead sponsor
- Can-Fite BioPharma
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Rabin Medical Center
- Responsible party
- Sponsor
- Investigators
- Zivit Harpaz, Study director, Can-Fite BioPharma Ltd
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04333472
- Sponsor's protocol ID
- CF101-241COVID-19
- Status last verified
- Mar 2022
- First submitted
- 1 Apr 2020
- Last updated
- 22 Apr 2022
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: To be determined
Publications
Fishman P, Cohen S. The A3 adenosine receptor (A3AR): therapeutic target and predictive biological marker in rheumatoid arthritis. Clin Rheumatol. 2016 Sep;35(9):2359-62. doi: 10.1007/s10067-016-3202-4. Epub 2016 Feb 17.
PubMed 26886128Cohen S, Fishman P. Targeting the A3 adenosine receptor to treat cytokine release syndrome in cancer immunotherapy. Drug Des Devel Ther. 2019 Jan 30;13:491-497. doi: 10.2147/DDDT.S195294. eCollection 2019.
PubMed 30787591
Study at a glance
From the registry record, last updated by the sponsor on 22 Apr 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Piclidenoson for Treatment of COVID-19 - A Randomized, Double-Blind, Placebo-Controlled Trial
- ClinicalTrials.gov ID
- NCT04333472
- Acronym / sponsor ID
- CF101-241COVID-19
- Conditions
- COVID-19, Coronavirus Infection
- Keywords
- Piclidenoson, CF101, SARS-CoV-2
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 6 participants (actual)
- Lead sponsor
- Can-Fite BioPharmaIndustry (pharma, biotech, devices)
- Collaborators
- Rabin Medical Center
- Study start
- 6 Jan 2021 (actual)
- Primary completion
- 6 Mar 2022 (actual)
- Study completion
- 21 Apr 2022 (actual)
- First posted
- 3 Apr 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Piclidenoson | Experimental | Drug: PiclidenosonPiclidenoson 2 mg every 12 hours orally added to standard of care |
| Placebo | Placebo comparator | Drug: PlaceboPlacebo every 12 hours orally added to standard of care |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (22 listed)
- Hospitalized subjects 18 to 85 years of age, inclusive
- Able and willing to sign informed consent
- Molecular (RT-PCR) diagnosis of SARS-CoV-2 infection
- Moderate or Severe illness per NIH COVID-19 Treatment Guidelines:
- 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
Key exclusion criteria (29 listed)
- 1. "Critical" Illness, per NIH COVID-19 Treatment Guidelines, including any of the following:
- Subjects who require mechanical ventilation or extracorporeal membrane oxygenation (ECMO)
- Participation in another clinical trial concurrently
- Concurrent treatment with immunomodulators or anti-rejection drugs
- Nursing women, pregnant women, women of childbearing potential who do not want adequate contraception
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PiclidenosonAlso: CF101Piclidenoson 2 mg orally every 12 hours for up to 28 days | Drug | Piclidenoson |
| PlaceboPlacebo orally every 12 hours for up to 28 days | Drug | Placebo |
Primary outcome
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
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
Treatment-emergent adverse events (AEs)
Time frame: 29 days
Proportion of patients experiencing AEs
16 secondary outcomes
Clinical status
Time frame: 29 days
Time to improvement
Time frame: 29 days
Incidence of mechanical ventilation
Time frame: 29 days
Ventilator-free days
Time frame: 29 days
Incidence of Intensive Care Unit (ICU) admission
Time frame: 29 days
Duration of ICU stay
Time frame: 29 days
Time to hospital discharge
Time frame: 29 days
Duration of need for supplemental oxygen
Time frame: 29 days
Time to virus negativity
Time frame: 29 days
SARS-CoV-2 viral load
Time frame: 29 days
AEs leading to withdrawal
Time frame: 29 days
Treatment-emergent serious AEs (SAEs)
Time frame: 29 days
Treatment-emergent abnormalities in clinical laboratory parameters or electrocardiograms (ECGs)
Time frame: 29 days
Incidence of meeting safety-related stopping rules
Time frame: 29 days
Pharmacokinetics of piclidenoson in this patient population
Time frame: 5 days
Serum cytokine levels
Time frame: 29 days
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Apr 2022.
- Background: PubMed 26886128Fishman P, Cohen S. The A3 adenosine receptor (A3AR): therapeutic target and predictive biological marker in rheumatoid arthritis. Clin Rheumatol. 2016 Sep;35(9):2359-62. doi: 10.1007/s10067-016-3202-4. Epub 2016 Feb 17.
- Background: PubMed 30787591Cohen S, Fishman P. Targeting the A3 adenosine receptor to treat cytokine release syndrome in cancer immunotherapy. Drug Des Devel Ther. 2019 Jan 30;13:491-497. doi: 10.2147/DDDT.S195294. eCollection 2019.
- Sponsor websiteLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. To be determined
Related trials for COVID-19
Not yet recruitingPhase 1
Phase I Open-Label Safety Trial of Pembrolizumab for Neurological Post- Acute Sequelae of SARS-CoV-2 (PD1-PASC I)
Post-Acute COVID-19 Syndrome
Active, not recruitingPhase 1
A Safety and Immunogenicity Trial of OCU500, ChAd36 Vector Encoding SARS-CoV-2 Spike Vaccine Via Intranasal and Inhalational Routes in Previously Vaccinated Adults
COVID-19
Active, not recruiting
Intervention to Address Disparate Mental Health Consequences of COVID-19 Pandemic on Latinx and African Newcomers
Mental Health Issue, Mental Health Disorder
Recruiting
Home-Based Exercise Tele-Rehabilitation After COVID-19
Post SARS-CoV2 (COVID-19)
Not yet recruitingPhase 1
A Safety, Reactogenicity and Immunogenicity Trial of RVX-sCPD9 Booster Intranasal COVID-19 Vaccine
COVID -19
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Zivit Harpaz study director
Can-Fite BioPharma Ltd
6 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Piclidenoson in people with COVID-19 and Coronavirus Infection, run by Can-Fite BioPharma at 6 sites in 3 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 22 inclusion and 29 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 22 Apr 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 6 sites in Bulgaria, Israel, Romania. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Proportion of subjects alive and free of respiratory failure (time frame: 29 days). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04333472, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Apr 2022.