This trial will test the hypothesis that the administration of CF101, a novel anti-inflammatory agent, to patients with moderate to severe plaque psoriasis will relieve signs and symptoms of the disease. CF101 effect will be in comparison to apremilast in this study population
This is a multicenter, randomized, double-blind, placebo- and active-controlled, study in adult males and females, aged 18 to 80 years, inclusive, with a diagnosis of moderate-to-severe chronic plaque psoriasis. Eligible subjects will be randomly assigned to CF101 2 mg, 3 mg, matching apremilast 30 mg BID, or matching placebo, in a 3:3:3:2 ratio. Blinding will be maintained using a double-dummy technique. Medication will be taken orally BID for 32 weeks in a double-blinded fashion, with the option to continue treatment through an Extension Period to 48 weeks. Subjects initially assigned to the placebo group will be re-randomized at Week 16 to either CF101 2 mg, CF101 3 mg, or apremilast (with appropriate dose titration) in a 1:1:1 ratio and treated through Week 32, while subjects originally assigned to 1 of the active treatment groups will remain on that treatment through Week 32. The primary efficacy endpoint will be assessed at Weeks 16 and 32; at Week 32, all subjects will be offered the opportunity to remain on their assigned blinded drug through Week 48 (ie, the Extension Period of Weeks 33-48). Disease will be assessed using PASI , static PGA , the percentage of BSA involved, and PDI. Subjects will return for assessments and a new supply of study medication at Weeks 4, 8, 12, 16, 20, 24, and 28, and for final study assessments at Week 32. For those subjects continuing into the Extension Period, efficacy and safety assessments will also occur at Weeks 36, 40, 44, and 48. PK will be assessed in a subgroup of approximately 120 subjects at Weeks 0, 8, 16, 24 and 32. PK will be assessed through sparse sampling. Assessment of whole blood A3AR expression levels will occur at Screening, Week 16, and Week 32.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
528
CF101 tablets, 2mg BID for 16 weeks
CF101 tablets, 3mg BID for 16 weeks
Apremilast tablets, 30mg BID for 16 weeks
Psoriasis Area and Severity Index (PASI) score response of ≥75% (PASI 75) at Week 16
Evaluate the efficacy of oral CF101 2 mg or 3 mg twice daily (BID) in patients 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 of ≥75% (PASI 75) at Week 16 (superiority)
Time frame: 16 weeks
Adverse event profile in this patient popluation
Nature, incidence and severity of treatment-emergent adverse events
Time frame: 16 weeks
Psoriasis Area and Severity Index (PASI) score response of ≥50% (PASI 50) at Week 16
Evaluate the efficacy of oral piclidenoson 2 mg or 3 mg BID, compared with placebo, as determined by the proportion of subjects who achieve PASI 50 at Week 16 (superiority);
Time frame: 16 weeks
Physician Global Assessment (PGA)
Evaluate the efficacy of oral piclidenoson 2 mg or 3 mg BID, compared with placebo, as determined by the proportion of subjects who achieve PGA score of 0 or 1 at Week 16;
Time frame: 16 weeks
Psoriasis Disability Index (PDI)
Evaluate the efficacy of oral piclidenoson 2 mg or 3 mg BID, compared with placebo, as determined by the proportion of subjects who achieve improvement on the PDI at Week 16;
Time frame: 16 weeks
CF101 PASI 75 compare to apremilast
Evaluate the efficacy of oral piclidenoson 2 mg or 3 mg BID, compared with apremilast, as determined by the proportion of subjects who achieve PASI 75 at Weeks 16 and 32;
Time frame: weeks 16-32
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Placebo tablets, BID for 16 weeks
Clinical Centre of Republika Srpska
Banja Luka, Bosnia and Herzegovina
University Clinical Centre Mostar
Mostar, Bosnia and Herzegovina
Clinical Centre of Sarajevo University
Sarajevo, Bosnia and Herzegovina
"Multiprofile Hospital for Active Treatment - Pazardzhik"
Pazardzhik, Bulgaria
"MHAT"Rahila Angelova"AD, Department of Skin and Venereal Diseases
Pernik, Bulgaria
"University Multiprofile Hospital for Active Treatment - D-r Georgi Stranski" - EAD, Pleven, Clinic of Skin and Venereal Diseases
Pleven, Bulgaria
"Diagnostic-Consultative Aleksandrovska" EOOD
Sofia, Bulgaria
"Diagnostic-Consultative Centre XX - Sofia" EOOD
Sofia, Bulgaria
Ambulatory for Specialized Medical Help - Group Practice Dermatology - Clinic EuroDerma" OOD
Sofia, Bulgaria
K. Papp Clinical Research
Waterloo, Canada
...and 20 more locations
CF101 PGA score compare to apremilast
Evaluate the efficacy of oral piclidenoson 2 mg or 3 mg BID, compared with apremilast, as determined by the proportion of subjects who achieve PGA score of 0 or 1, at Weeks 16 and 32;
Time frame: weeks 16-32
CF101 PASI 50 compare to apremilast
Evaluate the efficacy of oral piclidenoson 2 mg or 3 mg BID, compared with apremilast, as determined by the proportion of subjects who achieve PASI 50 at Weeks 16 and 32;
Time frame: weeks 16-32
CF101 PDI improvement compare to apremilast
Evaluate the efficacy of oral piclidenoson 2 mg or 3 mg BID, compared with apremilast, as determined by the proportion of subjects who achieve an improvement in PDI at Weeks 16 and 32;
Time frame: weeks 16-32
Apremilast PASI 75 compare to placebo
Establish assay sensitivity within this trial by comparing the efficacy of apremilast 30 mg BID with that of placebo tablets BID, as determined by the proportion of subjects who achieve PASI 75, PGA score of 0 or 1, PASI 50, and improvement in PDI at Week 16 (superiority);
Time frame: weeks 16-32
Apremilast PGA compare to placebo
Establish assay sensitivity within this trial by comparing the efficacy of apremilast 30 mg BID with that of placebo tablets BID, as determined by the proportion of subjects who achieve PGA score of 0 or 1 at Week 16;
Time frame: weeks 16-32
Apremilast PASI 50 compare to placebo
Establish assay sensitivity within this trial by comparing the efficacy of apremilast 30 mg BID with that of placebo tablets BID, as determined by the proportion of subjects who achieve PASI 50 at Week 16;
Time frame: weeks 16-32
Apremilast PDI compare to placebo
Establish assay sensitivity within this trial by comparing the efficacy of apremilast 30 mg BID with that of placebo tablets BID, as determined by the proportion of subjects who achieve improvement in PDI at Week 16;
Time frame: 16 weeks
Adverse event profile of piclidenoson through the Extension Period of up to 48 weeks of treatment
Nature, incidence, and severity of treatment-emergent adverse events
Time frame: 48 weeks
Efficacy of piclidenoson, as determined by changes in PASI score, through the Extension Period of up to 48 weeks of treatment
The proportion of subjects who achieve a Psoriasis Area and Severity Index (PASI) score response of ≥75% (PASI 75) at Week 48
Time frame: 48 weeks
Determine pharmacokinetics (PK) of piclidenoson under the circumstances of this trial using sparse sampling
Serum concentration of piclidenoson
Time frame: 48 weeks
Evaluate the relationship between pre-treatment whole blood A3 adenosine receptor (A3AR) expression levels and response to piclidenoson treatment.
Explore the relationship between white blood cell (WBC) adenosine A3 receptor (A3AR) expression and treatment response, by taking WBC sample at baseline
Time frame: 16 weeks