Efficacy and Safety of Oral Piclidenoson in Moderate-to-Severe Plaque Psoriasis: A Phase 3 Randomized, Double-Blind, Placebo-Controlled Trial

Trial ID: 2024-519919-34-00
Protocol: CF101-302PS
Sponsor: Can-Fite Biopharma Ltd.

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Diseases & Conditions

Psoriasis

Objectives

The primary objective of this Phase 3, randomized, double-blind, placebo-controlled study is to evaluate the **efficacy** and **safety** of oral piclidenoson 3 mg twice daily (BID) in subjects with moderate-to-severe **plaque psoriasis**. The efficacy will be assessed by the proportion of subjects achieving a Psoriasis Area and Severity Index (PASI) score response of ≥75% (PASI 75) and a Static Physician's Global Assessment (sPGA) score of 0 or 1 with at least a 2-point improvement from baseline at Week 16. The safety of oral piclidenoson in this population will also be evaluated. These objectives are clinically relevant as they aim to determine the potential of piclidenoson as a therapeutic option for improving the clinical outcomes and quality of life in patients with moderate-to-severe plaque psoriasis.

Secondary objectives include:

Evaluating the efficacy at Week 16 of oral piclidenoson 3 mg BID, compared with placebo, by the proportion of subjects achieving both PASI 75 and sPGA of 0 or 1 with at least a 2-point improvement from baseline, improvement of the Psoriasis Symptoms and Signs Diary (PSSD) to a score of 0 or 1, and improvement of the Dermatology Life Quality Index (DLQI) to a score of 0 or 1.
Determining the pharmacokinetics (PK) of piclidenoson under the circumstances of this trial using sparse sampling in Segment 2.

These secondary objectives are important for understanding the broader impact of piclidenoson on patient-reported outcomes and its pharmacokinetic profile, which can inform dosing strategies and patient management.

Participants

The clinical trial involves participants diagnosed with **plaque psoriasis**, specifically targeting individuals with moderate-to-severe chronic plaque-type psoriasis. The study population includes both male and female subjects aged 18 years and above. Participants are required to have a Body Surface Area (BSA) involvement of at least 10%, a Psoriasis Area and Severity Index (PASI) score of 12 or higher, and a Static Physician's Global Assessment (sPGA) score of 3 or more at both the Screening and Baseline visits. The trial does not include a vulnerable population. Participants must be candidates for systemic treatment or phototherapy and have had psoriasis for a minimum duration of 12 months. Females of childbearing potential are required to have a negative serum pregnancy test at screening and must use at least one acceptable contraceptive method throughout the trial and for one month after the last dose of study medication. Male participants must refrain from sperm donation and agree to use condoms during the trial and for one month after the last dose of study medication. The sponsor has not provided information regarding the total number of participants in the trial.

Plans and Procedures

The clinical trial is a **Phase 3**, randomized, double-blind, placebo-controlled study designed to evaluate the efficacy and safety of daily oral administration of **Piclidenoson** in subjects with moderate-to-severe **plaque psoriasis**. The trial aims to assess the proportion of subjects achieving a Psoriasis Area and Severity Index (PASI) score response of at least 75% (PASI 75) and a Static Physician's Global Assessment (sPGA) score of 0 or 1 with at least a 2-point improvement from baseline at Week 16. The study will also evaluate the safety profile of Piclidenoson in this population.

The trial is expected to commence recruitment on April 28, 2025, and conclude by January 31, 2028. Participants will be involved in the study for a maximum treatment period of 52 weeks. The study will include an initial screening visit to confirm eligibility based on criteria such as age, diagnosis of moderate-to-severe plaque psoriasis, and other health parameters. Eligible participants will be randomized to receive either Piclidenoson or a matching placebo, administered orally in tablet form.

Study visits will be scheduled at regular intervals to monitor the participants' health status, adherence to the treatment regimen, and response to the medication. These visits will include assessments of PASI and sPGA scores, as well as safety evaluations. The end-of-study visit will occur after the completion of the treatment period, where final assessments will be conducted to evaluate the primary and secondary endpoints.

Participants may be withdrawn from the study early if they experience significant adverse events, fail to comply with the study protocol, or choose to withdraw consent. The trial's design ensures that all data collected will contribute to understanding the therapeutic potential and safety of Piclidenoson in treating plaque psoriasis.

Treatment

The clinical trial involves the administration of **Piclidenoson**, an experimental medication, in the form of a **tablet**. Piclidenoson is chemically derived and is provided by CAN-FITE BIOPHARMA LTD. The active substance in this medication is piclidenoson, also known by the product code CF101. The medication is administered orally at a dosage of 3 mg twice daily (BID) to participants with moderate-to-severe plaque psoriasis. The maximum daily dose is 6 mg, and the total maximum dose over the treatment period is 312 mg. The treatment duration is set for a maximum of 52 weeks. Compliance with the dosing schedule is monitored throughout the study to ensure adherence to the protocol.

The study also includes a **matching placebo** for Piclidenoson, which is used as a comparator treatment. The placebo is designed to mimic the appearance and administration route of the active medication, ensuring the study remains double-blind. The placebo is administered orally in the same frequency and form as Piclidenoson, maintaining the integrity of the study's design. The use of a placebo allows for the evaluation of Piclidenoson's efficacy and safety by comparing outcomes between the active treatment group and the placebo group.

Efficacy

The efficacy of Piclidenoson in the treatment of moderate-to-severe plaque psoriasis will be assessed through a Phase 3, randomized, double-blind, placebo-controlled study. The primary efficacy endpoints include the proportion of subjects achieving a **Psoriasis Area and Severity Index (PASI)** score response of at least 75% improvement (PASI 75) at Week 16, and the proportion of subjects achieving a Static Physician's Global Assessment (sPGA) score of 0 or 1 with at least a 2-point improvement from Baseline at Week 16. Secondary efficacy endpoints will evaluate the proportion of subjects achieving both PASI 75 and sPGA of 0 or 1 with at least a 2-point improvement from Baseline at Week 16, as well as improvements in the Psoriasis Symptom Severity Diary (PSSD) and Dermatology Life Quality Index (DLQI) to scores of 0 or 1 at Week 16.

Data collection will occur at specified timepoints, with primary assessments conducted at Week 16. The PASI and sPGA scores will be utilized as validated scales to measure the severity and extent of psoriasis. Additional assessments will include changes from Baseline in PASI score, percentage of Body Surface Area (BSA) involved, and scores on the PSSD and DLQI. For Segment 2 of the study, additional endpoints will include the percentage change from Baseline in the Psoriasis Scalp Severity Index (PSSI) and Nail Psoriasis Severity Index (NAPSI), as well as the time to psoriasis relapse during the placebo-controlled withdrawal period. The analysis will focus on comparing the efficacy of Piclidenoson 3 mg administered orally twice daily against a matching placebo.

Inclusion and Exclusion Criteria

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Inclusion Criteria

Male or female, 18 years and above
Diagnosis of moderate-to-severe chronic plaque-type psoriasis with BSA involvement ≥10%
PASI score ≥12 at the Screening and Baseline visits
Static PGA ≥3 at the Screening and Baseline visits
Candidate for systemic treatment or phototherapy for psoriasis
Duration of psoriasis of at least 12 months
Females of childbearing potential must have a negative serum pregnancy test at screening
Female subjects of childbearing potential must use at least one acceptable contraceptive method (as described in Section 10.7) throughout the course of the trial and for 1 month after the last dose of study medication
Male subjects must refrain from sperm donation during treatment and until at least 1 month after the last dose of study medication. Male subjects must agree to use condoms throughout the course of the trial and for 1 month after the last dose of study medication
Ability to complete the study in compliance with the protocol
Ability to understand and provide written informed consent

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Exclusion Criteria

Psoriasis limited to erythrodermic, guttate, palmar, plantar, or generalized pustular psoriasis in the absence of plaque psoriasis
Treatment with systemic retinoids, systemic corticosteroids, tofacitinib, apremilast, immunosuppressive agents (e.g., methotrexate, cyclosporine), or any other approved drugs for the indication of plaque psoriasis (e.g., deucravacitinib) within 4 weeks of the Baseline visit
Treatment with a monoclonal antibody or other biologic agent for psoriasis within 8 weeks for etanercept, adalimumab, or infliximab, or within 12 weeks for all other agents, prior to the Baseline visit
Treatment with Vitamin D analogs, keratolytics, coal tar (other than on the scalp, palms, groin, and/or soles), any topical corticosteroid, calcineurin inhibitors, vitamin A analogs, retinoids, anthralin, calcipotriene, tazarotene, methoxsalen, trimethylpsoralens, fumarate, PDE4 inhibitors, or aryl hydrocarbon receptormodulating agents within 2 weeks of the Baseline visit
Ultraviolet or Dead Sea therapy within 4 weeks of the Baseline visit, or anticipated need for either of these therapies during the study period
Treatment with lithium, hydroxychloroquine or chloroquine within 2 weeks of the Baseline visit, or anticipated need for such drugs during the study period, unless dose has been stable for 3 months prior to the Screening visit and will remain stable throughout the trial
Estimated glomerular filtration rate (eGFR) <50 mL/min/1.73m2 by the Modification of Diet in Renal Disease equation at Screening (NOTE: In Segment 2, a renally-impaired subgroup of at least 10-12 subjects with eGFR of 20-49 mL/min/1.73m2 will be enrolled for PK analysis purposes)
Liver aminotransferase levels greater than 1.5 times the laboratory’s upper limit of normal at Screening
QTcF interval > 450 milliseconds (msec) for males or > 470 msec for females on Screening Visit and Baseline visit ECGs (average of triplicate ECGs at each visit) (except when QT prolongation is associated with right or left bundle branch block or cardiac pacemaker, in which case enrollment is allowed)
A condition which increases proarrhythmic risk, including hypokalemia, hypomagnesemia, or congenital Long QT Syndrome
Ongoing or planned use of a concomitant medication that is on the CredibleMedsTM list of drugs known to cause Torsades des Pointes
Active gastrointestinal disease which could interfere with the absorption of oral medication
Pregnancy, planned pregnancy, lactation, or inadequate contraception as judged by the Investigator
Active drug or alcohol dependence
Concomitant use of strong cytochrome P450 inducers, e.g., rifampin, phenobarbital, phenytoin, carbamazepine
PHQ-9 score ˃ 4 at baseline
Any significant/uncontrolled neuropsychiatric illness judged as clinically significant by the investigator during screening or at Day 1, or any lifetime history of suicidal ideation, suicidal behavior, or suicidal attempts by medical history or by Columbia Suicide Severity Rating Scale (C-SSRS) documentation, or by answering “yes” to Question 4 or 5 for suicidal ideation on the C-SSRS at screening or at Day 1, or is clinically deemed to have a suicide risk by the investigator
Previous participation in a piclidenoson (CF101) clinical trial
Significant acute or chronic medical or psychiatric illness that, in the judgment of the Investigator, could compromise subject safety, limit the subject’s ability to complete the study, and/or compromise the objectives of the study
Participation in another investigational drug or vaccine trial concurrently or within 30 days prior to the Screening visit