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
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 248
- 试验地点
- 12
- 主要终点
- For Segment 2 only: Percentage Change from Baseline in PSSI
研究概览
简要总结
The co-primary efficacy objectives of this study for all subjects (Segments 1 and 2) are to: • Evaluate the efficacy of oral piclidenoson 3 mg twice daily (BID) in subjects with moderate-to-severe plaque psoriasis, compared with placebo, as determined by the proportion of subjects who achieve a Psoriasis Area and Severity Index (PASI) score response at Week 16 of ≥75% (PASI 75); and • Evaluate the efficacy of oral piclidenoson 3 mg BID in subjects with moderate-to-severe plaque psoriasis, compared with placebo, as determined by the proportion of subjects who achieve a Static Physician's Global Assessment (sPGA) at Week 16 of 0 or 1 with at least a 2-point improvement from Baseline. The primary safety objective of this study for all subjects (Segments 1 and 2) is to: • Evaluate the safety of oral piclidenoson in this population.
研究设计
- 分配方式
- Randomized
- 主要目的
- Segment 2
- 盲法
- Double (Analyst, Monitor, Investigator, Subject)
入排标准
- 年龄范围
- 18 years 至 65+ years（18-64 Years, 65+ Years）
- 接受健康志愿者
- 否
入选标准
- •Male or female, 18 years and above
- •Ability to complete the study in compliance with the protocol
- •Ability to understand and provide written informed consent
- •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
排除标准
- •Psoriasis limited to erythrodermic, guttate, palmar, plantar, or generalized pustular psoriasis in the absence of plaque psoriasis
- •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
- •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
- •Participation in another investigational drug or vaccine trial concurrently or within 30 days prior to the Screening 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)
结局指标
主要结局
For Segment 2 only: Percentage Change from Baseline in PSSI
For Segment 2 only: Percentage Change from Baseline in PSSI
For Segment 2 only: Percentage Change from Baseline in NAPSI
For Segment 2 only: Percentage Change from Baseline in NAPSI
For Segment 2 only: Time to psoriasis relapse during the placebo-controlled withdrawal period
For Segment 2 only: Time to psoriasis relapse during the placebo-controlled withdrawal period
Proportion of subjects achieving PASI 75
Proportion of subjects achieving PASI 75
Proportion of subjects achieving sPGA of 0 or 1 with at least a 2- point improvement from Baseline
Proportion of subjects achieving sPGA of 0 or 1 with at least a 2- point improvement from Baseline
Proportion of subjects achieving PASI 50, PASI 90, or PASI 100
Proportion of subjects achieving PASI 50, PASI 90, or PASI 100
Proportion of subjects achieving both PASI 75 and sPGA of 0 or 1 with at least a 2-point improvement from Baseline
Proportion of subjects achieving both PASI 75 and sPGA of 0 or 1 with at least a 2-point improvement from Baseline
Change from Baseline and Percent Change from Baseline in PASI score
Change from Baseline and Percent Change from Baseline in PASI score
Proportion of subjects achieving PSSD of 0 or 1
Proportion of subjects achieving PSSD of 0 or 1
Proportion of subjects achieving DLQI of 0 or 1
Proportion of subjects achieving DLQI of 0 or 1
Change from Baseline in percentage of BSA involved
Change from Baseline in percentage of BSA involved
Change from Baseline in PSSD
Change from Baseline in PSSD
Change from Baseline in DLQI
Change from Baseline in DLQI
For Segment 2 only: Proportion of subjects who experience a psoriasis relapse during the placebo-controlled withdrawal period
For Segment 2 only: Proportion of subjects who experience a psoriasis relapse during the placebo-controlled withdrawal period
For Segment 2 only: Proportion of subjects who experience a psoriasis relapse and subsequently achieve PASI 75 during retreatment with piclidenoson
For Segment 2 only: Proportion of subjects who experience a psoriasis relapse and subsequently achieve PASI 75 during retreatment with piclidenoson
次要结局
- Proportion of subjects who achieve both PASI 75 and sPGA of 0 or 1 with at least a 2-point improvement from Baseline at Week 16
- Proportion of subjects who achieve improvement of the PSSD to a score of 0 or 1 at Week 16
- Proportion of subjects who achieve improvement of the DLQI to a score of 0 or 1 at Week 16
研究者
Zivit Harpaz
Scientific
Can-Fite Biopharma Ltd.