Safety and Efficacy Study of CF101 to Treat Psoriasis

A Phase 2, Randomized, Double-Blind, Dose-Ranging, Placebo-Controlled Study of the Safety and Activity of Daily CF101 Administered Orally in Patients With Moderate-to-Severe Plaque Psoriasis

This study will test the hypothesis that CF101, which is under development to treat other immune-mediated inflammatory diseases, will provide clinical benefits in the treatment of chronic plaque psoriasis. Patients with psoriasis who qualify for the study will be treated every 12 hours (q12h) with CF101 capsules, or placebo capsules, for 12 weeks. The safety of treatment will be carefully assessed through clinical and laboratory monitoring. The effect of treatment on psoriasis will be evaluated through standard techniques of examination and measurement of the severity of skin involvement.

This is a Phase 2, multicenter, randomized, double-blind, dose-ranging, placebo-controlled, study in adult males and females, ages 18 to 70 years, inclusive, with a diagnosis of moderate-to-severe chronic plaque psoriasis. At the Screening Visit, patients who provide written informed consent will have screening procedures performed, including a complete medical history, medication history, physical examination, including height, weight, blood pressure, pulse rate and temperature, and clinical laboratory tests.

Eligible patients will be those who have not received systemic retinoids, corticosteroids, or immunosuppressants (e.g., methotrexate, cyclosporine) within 6 weeks prior to initiation of study; or high potency topical corticosteroids (Class I-III), keratolytics, or coal tar (other than on the scalp, palms, groin, and/or soles); and UV or Dead Sea therapy within 4 weeks prior to initiation of study treatment. Eligible patients will be sequentially assigned to 1 of 3 dosing cohorts:

Cohort 1: CF101 1 mg (15 patients) or Placebo (5 patients); Cohort 2: CF101 2 mg (15 patients) or Placebo (5 patients); Cohort 3: CF101 4 mg (15 patients) or Placebo (5 patients).

Medication will be taken orally q12h for 12 weeks. Disease activity will be assessed using the Psoriasis Area and Severity Index (PASI) and the Physician Global Assessment (PGA). Patients will return for assessments at Weeks 2, 4, 8, 12 and 14.

Inclusion Criteria:

• Male or female, 18 to 70 years of age, inclusive;
• Diagnosis of moderate-to-severe chronic plaque-type psoriasis with body surface area involvement ≥10%, as judged by the Investigator;
• Duration of psoriasis of at least 6 months;
• PASI score ≥10;
• Body weight ≤100 kg;
• Candidate for systemic treatment or phototherapy for psoriasis;
• ECG is normal or shows abnormalities which, in the judgment of the Investigator, are not clinically significant;
• Females of child-bearing potential must have a negative serum pregnancy test at screening;
• Females of child-bearing potential must be willing to use 2 methods of contraception deemed adequate by the Investigator (for example oral contraceptive pills plus a barrier method) to be eligible for, and continue participation in, the study;
• Ability to complete the study in compliance with the protocol; and
• Ability to understand and provide written informed consent.

Exclusion Criteria:

• Erythrodermic, guttate, palmar, plantar, or generalized pustular psoriasis;
• Treatment with systemic retinoids, corticosteroids, or immunosuppressants (e.g., methotrexate, cyclosporine) within 6 weeks of the Baseline visit;
• Treatment with high potency topical corticosteroids (Class I-III), keratolytics, or coal tar (other than on the scalp, palms, groin, and/or soles) 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 a biological agent (including etanercept, adalimumab, efalizumab, infliximab, or alefacept) within a period of time equal to 5 times its circulating half-life, or 30 days, whichever is longer, prior to the Baseline visit;
• History of poor clinical response to methotrexate after an adequate regimen and duration of treatment;
• Treatment with systemic nonsteroidal anti-inflammatory drugs, beta-blockers, lithium, hydroxychloroquine, chloroquine, or systemic terbinafine within 2 weeks of the Baseline visit, or anticipated need for such drugs during the study period;
• Presence or history of uncontrolled asthma;
• Presence or history of uncontrolled arterial hypertension or symptomatic hypotension;
• Significant cardiac arrhythmia or conduction block, congestive heart failure (New York Heart Association Class 3-4), or any other evidence of clinically significant heart disease or clinically significant findings on screening electrocardiogram;
• Hemoglobin level <9.0 gm/L;
• Platelet count <125,000/mm^3;
• White blood cell count <3500/mm^3;
• Serum creatinine level greater than 1.5 times the laboratory's upper limit of normal;
• Liver aminotransferase levels greater than 2 times the laboratory's upper limit of normal;
• Pregnancy, planned pregnancy, lactation, or inadequate contraception as judged by the Investigator;
• History of malignancy within the past 5 years (excluding basal cell carcinoma of the skin and ≤3 cutaneous squamous cell carcinomas, all of which have been completely excised);
• Significant acute or chronic medical or psychiatric illness that, in the judgment of the Investigator, could compromise patient safety, limit the patient'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; or within 5 half lives of a biological investigational product, whichever is longer;
• Other conditions which would confound the study evaluations or endanger the safety of the patient.