• Improvement in Target Lesion Score at Week 4
  

• Changes in target lesion pruritus Visual Analog Scale (VAS) at Week 4
  

Psoriasis is a hyperproliferative, inflammatory, immune-mediated skin disease that affects approximately 2% of the United States and European populations (Tutrone 2001, Kipnis 2005). This disease manifests as red, scaly plaques that are itchy and/or painful. Patients with psoriasis may be socially stigmatized because of their appearance. Currently, there is no cure for this condition. Often, repeated medical treatments are necessary and can become expensive. Treatment with topical corticosteroids is the mainstay therapy for mild to moderate psoriasis. In more severe cases, systemic therapies (e.g., cyclosporine) and phototherapy (e.g., UVB irradiation) are used. These treatments, however, are associated with toxicities or inconvenience. There is anecdotal evidence to suggest that antipsychotic drugs have a beneficial effect on psoriasis (Gupta 2001, 2003).

Fluphenazine is a phenothiazine antipsychotic drug. In vitro, fluphenazine kills activated human T cells under conditions that do not affect resting T cells (Immune Control Inc. data not shown). To determine the size of a therapeutic window for human PBMCs, Immune Control Inc. performed the following experiments. First, PHA-activated cells were exposed to 2, 10, or 20 µM fluphenazine for 0, 18, 24, 36, 48, or 72 hours. Second, resting cells were exposed to identical fluphenazine concentrations for identical time periods, after which the drug was washed out of the cells, and the cells activated with PHA. In all cases, DNA synthesis was measured by exposing the cells to tritiated thymidine, and measuring the incorporated nucleotide by scintillation counting. The data show that exposure of activated cells to 10 µM fluphenazine for 72 hours, or 20 µM fluphenazine for 36 hours, caused the death of virtually all of the activated cells. The ability of the resting cells to initiate DNA synthesis after activation, by contrast, was largely unaffected by these fluphenazine exposures. Although we cannot precisely control intralesional fluphenazine concentrations, we expect that injections of up to 1 mg fluphenazine decanoate will yield local concentrations that exceed 10 µM without significant systemic fluphenazine concentrations.

We propose that fluphenazine will suppress proliferating T-lymphocytes in psoriatic plaques in vivo and thus result in healing of plaques. The objective of this study is to assess the safety and biologic activity of intralesional injection of fluphenazine decanoate in adult subjects with psoriasis.

Inclusion Criteria:

• Adults 18 to 65 years of age with psoriasis, in general good health
• Must have symmetric target lesions approximately 2-4 cm in diameter on each side of the body (e.g., thighs) with baseline target lesion score of 6 or higher (scale of 0-12) for each target
• Women of childbearing potential must agree to use two forms of contraception for the duration of the study

Exclusion Criteria:

• Infliximab (Remicade) or alefacept (Amevive) within the past 6 months (24 weeks)
• Etanercept (Enbrel), efalizumab (Raptiva), adalimumab (Humira), or other TNF-alpha inhibitor within the past 3 months (12 weeks)
• Other systemic psoriasis therapies (e.g., methotrexate, cyclosporine, acitretin) or PUVA (psoralen plus UVA) within the past 4 weeks
• UVB or topical therapy (other than OTC moisturizers and shampoos) within the past 2 weeks (including topical corticosteroids, vitamin A and D analogues)
• Receipt of an investigational agent within the past 4 weeks
• Systemic corticosteroid therapy
• Inability to understand consent or comply with protocol
• Pregnancy, lactation, or unwillingness to use adequate birth control during the study
• Impaired hepatic function
• Known HIV/AIDS, hepatitis B/C
• Blood dyscrasia
• Epilepsy
• Tardive dyskinesia
• Excessive alcohol consumption
• Current use of SSRI, tricyclic, or norephinephrine reuptake inhibitor antidepressants or use within 6 weeks of beginning the study
• Concurrent use of anti-seizure drugs, with the exception of gabapentin for treatment of neuropathy
• Use of phenothiazine antipsychotics or anticholinergics
• Known allergy to fluphenazine decanoate or other phenothiazines
• Known allergy to parabens/PABA, benzyl alcohol, sesame oil or sesame seeds
• Clinically significant mitral valve disease
• Clinically significant and uncontrolled cardiovascular disease
• QTc >450 msec, or evidence of a clinically significant dysrhythmia on ECG
• Operator of heavy machinery
• Pheochromocytoma
• History of breast cancer
• History of seizure disorder
• Occupational exposure to organophosphate insecticides
• Parkinson's disease and other related movement disorders
• Lab abnormalities including:
• AST/ALT ≥ 2X upper limit of reference range
• Creatinine ≥ 1.5X upper limit of reference range
• Bilirubin ≥ 2X upper limit of reference range
• Absolute total lymphocyte or polymorphonuclear leucocyte count ≤ 1000/uL or ≥ 3X upper limit of ref range
• Platelets ≤ 80,000/uL
• Hemoglobin ≤ 8.0 g/dL
• Glucose ≥ 200 mg/dL
• Fasting blood sugar ≥ 126 mg/dL
• Concurrent use of drugs listed in Appendix F