Psoriasis
Conditions
Brief summary
We are doing this research study to evaluate the effectiveness and safety of fluphenazine decanoate when injected with a needle into psoriasis lesions in adults. Fluphenazine decanoate is FDA (U.S. Food and Drug Administration) approved for use in people who have schizophrenia and psychotic symptoms. Fluphenazine decanoate is not approved by the FDA for use in psoriasis. Fluphenazine decanoate slows T cell growth in cells in laboratory test tubes. Its usefulness and safety in people with psoriasis will be investigated in this study.
Detailed description
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., ultraviolet B (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 peripheral blood mononuclear cells (PBMC)s, Immune Control Inc. performed the following experiments. First, phytohemagglutinin- (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, deoxyribonucleic acid (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.
Interventions
Fluphenazine decanoate marketed by APP Pharmaceuticals (25 mg/mL, 5 mL vial) was used in this study. This was an ascending dose study with the first cohort of 5 subjects dosed at 10 µg/mL, followed by 5 subject dosed in the second cohort at 100 µg/mL. Note: APP Pharmaceuticals is the name of the pharmaceutical company; APP is not an acronym.
DRUGPlacebo
The sterile placebo (sesame oil with 1.2% (w/v) benzyl alcohol) was prepared at the University of Iowa, Division of Pharmaceutical Services, a FDA registered pharmaceutical manufacturing facility.
Sponsors
Immune Control
Tufts Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
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 tumor necrosis factor- (TNF)-alpha inhibitor within the past 3 months (12 weeks) * Other systemic psoriasis therapies (e.g., methotrexate, cyclosporine, acitretin) or PUVA (psoralen plus ultraviolet A) within the past 4 weeks * Ultraviolet B (UVB) or topical therapy (other than over the counter (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 Human immunodeficiency virus (HIV)/acquired immune deficiency syndrome (AIDS), hepatitis B/C * Blood dyscrasia * Epilepsy * Tardive dyskinesia * Excessive alcohol consumption * Current use of selective serotonin reuptake inhibitors (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/para-aminobenzoic acid (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 electrocardiography (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: * Alanine aminotranferease (ALT)/aspartate aminotransferase (AST) ≥ 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Target Lesion Score at Week 4 Compared to Baseline | Baseline to week 4 | Change in score from 0-14 of target lesion disease activity based on scaling, erythema, and induration as determined by a physician assessor at week 4 compared to baseline (with 0 being no disease activity and 14 being maximum disease activity). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Target Lesion Pruritus Visual Analog Scale (VAS) at Week 4 Compared to Baseline. | Baseline to week 4 | Target lesion pruritus as measured by the Visual Analog Scale (VAS) from 0 to 100 mm at week 4 compared to baseline (with 0 being no pruritis and 100 being maximum pruritis). |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Cohort 1: 10 ug/ml Fluphenazine Decanoate Receiving fluphenazine decanoate (10 ug/ml) in a target lesion on one side of the body and placebo in a lesion on the other side of the body | 5 |
| Cohort 2: 100 ug/ml Fluphenazine Decanoate Receiving fluphenazine decanoate (100 ug/ml) in a target lesion on one side of the body and placebo in a lesion on the other side of the body | 5 |
| Total | 10 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Cohort 1: 10 ug/ml | Lack of Efficacy | 1 | 0 |
| Cohort 2: 100 ug/ml (New Patients) | Lack of Efficacy | 0 | 2 |
Baseline characteristics
| Characteristic | Cohort 2: 100 ug/ml Fluphenazine Decanoate | Cohort 1: 10 ug/ml Fluphenazine Decanoate | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 5 Participants | 5 Participants | 10 Participants |
| Age Continuous | 38.8 years STANDARD_DEVIATION 6.69 | 41.6 years STANDARD_DEVIATION 11.7 | 39.1 years STANDARD_DEVIATION 8.99 |
| Region of Enrollment United States | 5 participants | 5 participants | 10 participants |
| Sex: Female, Male Female | 2 Participants | 1 Participants | 3 Participants |
| Sex: Female, Male Male | 3 Participants | 4 Participants | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 4 / 5 | 4 / 5 |
| serious Total, serious adverse events | 0 / 5 | 0 / 5 |
Outcome results
Primary
Change in Target Lesion Score at Week 4 Compared to Baseline
Change in score from 0-14 of target lesion disease activity based on scaling, erythema, and induration as determined by a physician assessor at week 4 compared to baseline (with 0 being no disease activity and 14 being maximum disease activity).
Time frame: Baseline to week 4
Population: all 5 patients per cohort completed the visit at week 4
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1, 10 ug/ml Fluphenazine Treated Lesion | Change in Target Lesion Score at Week 4 Compared to Baseline | -1 units on a scale | Standard Deviation 2.45 |
| Cohort 1, Placebo Treated Lesion | Change in Target Lesion Score at Week 4 Compared to Baseline | -0.8 units on a scale | Standard Deviation 2.68 |
| Cohort 2, 100 ug/ml Fluphenazine Treated Lesion | Change in Target Lesion Score at Week 4 Compared to Baseline | -0.4 units on a scale | Standard Deviation 2.19 |
| Cohort 2, Placebo Treated Lesion | Change in Target Lesion Score at Week 4 Compared to Baseline | -1.5 units on a scale | Standard Deviation 2.4 |
Secondary
Change in Target Lesion Pruritus Visual Analog Scale (VAS) at Week 4 Compared to Baseline.
Target lesion pruritus as measured by the Visual Analog Scale (VAS) from 0 to 100 mm at week 4 compared to baseline (with 0 being no pruritis and 100 being maximum pruritis).
Time frame: Baseline to week 4
Population: all 5 patients per cohort completed the visit at week 4
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1, 10 ug/ml Fluphenazine Treated Lesion | Change in Target Lesion Pruritus Visual Analog Scale (VAS) at Week 4 Compared to Baseline. | -30 mm | Standard Deviation 35.07 |
| Cohort 1, Placebo Treated Lesion | Change in Target Lesion Pruritus Visual Analog Scale (VAS) at Week 4 Compared to Baseline. | -27.2 mm | Standard Deviation 34.69 |
| Cohort 2, 100 ug/ml Fluphenazine Treated Lesion | Change in Target Lesion Pruritus Visual Analog Scale (VAS) at Week 4 Compared to Baseline. | -18 mm | Standard Deviation 34.87 |
| Cohort 2, Placebo Treated Lesion | Change in Target Lesion Pruritus Visual Analog Scale (VAS) at Week 4 Compared to Baseline. | -32.6 mm | Standard Deviation 31.81 |