A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study of the Efficacy and Safety of Daily Piclidenoson (CF101) Administered Orally in Subjects With Moderate-to-Severe Plaque Psoriasis
Trial Snapshot
- Phase
- Phase 3
- Status
- Not yet recruiting
- Sponsor
- Can-Fite BioPharma
- Enrollment
- 705
- Primary Endpoint
- Proportion of subjects who achieve a Psoriasis Area and Severity Index (PASI) score response of ≥75% (PASI 75)
Study Overview
Brief Summary
This is a double-blind, placebo-controlled study in adults with a diagnosis of moderate-to-severe chronic plaque psoriasis to test the efficacy and safety of piclidenoson in this patient population.
Detailed Description
This is a multicenter, randomized, double-blind, placebo-controlled study in adult males and females, aged 18 years and above, with a diagnosis of moderate-to-severe chronic plaque psoriasis.
This trial will be conducted in 2 sequential Segments. When the required number of subjects have completed Segment 1, enrollment will be paused to perform an interim analysis for futility. If futility is not declared, enrollment in Segment 2 will commence. No subject will participate in both Segment 1 and Segment 2.
For subjects in Segment 1, the design is as follows:
At the Screening Visit (Visit 1, performed within 4 weeks prior to randomization), subjects who provide written informed consent will have screening procedures performed, including a complete medical history, medication history, physical examination (including height, weight, sitting blood pressure, respiratory rate, pulse rate and temperature), ECG, Patient Health Questionnaire-9 (PHQ-9), Columbia Suicide Severity Rating Scale (C-SSRS), and assessment of psoriasis (including Psoriasis Area and Severity Index (PASI), Static Physician's Global Assessment (sPGA), Body Surface Area (BSA) involved, Psoriasis Symptoms and Signs Diary (PSSD), and Dermatology Life Quality Index (DLQI)), and clinical laboratory tests.
For subjects enrolled in Segment 2, the design is as follows:
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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 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; and
- •Ability to understand and provide written informed consent.
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, trimethyl-psoralens, fumarate, PDE4 inhibitors, or aryl hydrocarbon receptor-modulating 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; and
- •Participation in another investigational drug or vaccine trial concurrently or within 30 days prior to the Screening visit.
Arms & Interventions
Piclidenoson treatment
Intervention: piclidenoson (Drug)
Placebo
Intervention: Placebo (Drug)
Outcomes
Primary Outcomes
Proportion of subjects who achieve a Psoriasis Area and Severity Index (PASI) score response of ≥75% (PASI 75)
Time Frame: 16 weeks
Improvement of psoriasis by 75% or more
proportion of subjects who achieve a Static Physician's Global Assessment (sPGA) of 0 or 1 with at least a 2-point improvement from Baseline
Time Frame: 16 weeks
Improvement of psoriasis by physicians' judgment
Proportion of subjects who experience adverse events
Time Frame: 52 weeks
All adverse events occurring the trial will be recorded
Secondary Outcomes
- Efficacy as determined by the proportion of subjects who achieve both PASI 75 and sPGA of 0 or 1 with at least a 2-point improvement from Baseline(16 weeks)
- Efficacy as determined by the proportion of subjects who achieve improvement of the Psoriasis Symptoms and Signs Diary (PSSD) to a score of 0 or 1(16 weeks)
- Efficacy as determined by the proportion of subjects who achieve improvement of the Dermatology Life Quality Index (DLQI) to a score of 0 or 1(16 weeks)