Psoriasis
Conditions
Keywords
Psoriasis, T-lymphocytes, Fluphenazine
Brief summary
The objective of this study is to assess the safety and biologic activity of intralesional injection of fluphenazine in adult subjects with psoriasis.
Detailed description
This is a double-blind, placebo-controlled, bilateral, ascending dose study. In vitro, fluphenazine has been shown to suppress growth of proliferating T-lymphocytes. Fluphenazine would be expected to also suppress growth of proliferating T-lymphocytes in psoriatic plaques.
Interventions
DRUGFluphenazine
Intralesional injection of Fluphenazine
DRUGPlacebo
Intralesional injection of placebo
Sponsors
Immune Control
Tufts Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
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 as determined by the Principal Investigator based upon the results of medical history, laboratory profile, and physical examination * Must have symmetric target lesions 2-4 cm in diameter on each side of the body (e.g., thighs) with baseline Target Lesion Score (TLS) of 6 or higher (scale of 0-12) for each target * Women are eligible to participate in the study if they meet one of the following criteria: * Women who are postmenopausal (for at least one year), sterile, or hysterectomized * Women of childbearing potential must undergo monthly pregnancy testing during the study and agree to use two of the following methods of contraception throughout the study and for 60 days after the last dose of study drug: * Oral contraceptives * Transdermal contraceptives * Injectable or implantable methods * Intrauterine devices * Barrier methods (diaphragm with spermicide, condom with spermicide) (Abstinence and Tubal Ligation are also considered a form of Birth control.)
Exclusion criteria
* Patient is not asymptomatic and has major ailments on screening exam. * 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 oral psoralen with ultraviolet A (PUVA) 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) with the exception of betamethasone valerate lotion (0.01%) for treatment of scalp lesions, and triamcinolone cream (0.1%) for lesions at least 3 inches away from the target lesions * Receipt of an investigation agent within the past 4 weeks * Systemic corticosteroid therapy * Inability to understand consent or comply with protocol (patients will be asked if they understand or have any questions) * 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 (drinking more than two drinks per day on average for men or more than one drink per day on average for women) * Use of phenothiazine antipsychotics or anticholinergics * Current use of selective serotonin reuptake inhibitor (SSRI), tricyclic, or norepinephrine 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 * Known allergy to fluphenazine or other phenothiazines, sesame oil or sesame seeds * Known allergy to parabens, para-aminobenzoate (PABA) or benzyl alcohol * Clinically significant and uncontrolled cardiovascular disease * corrected QT interval (QTc) \> 450 msec, or evidence of a clinically significant dysrhythmia on ECG * Operator of heavy machinery * Pheochromocytoma * Clinically significant mitral valve disease * History of breast cancer * History of seizure disorder * Occupational exposure to organophosphate insecticides * Parkinson's disease and other related movement disorders * Screening Lab abnormalities including: * Serum Asparate transaminase (AST) or Alanine transaminase (ALT) \> 2.5 upper limits of normal * Creatinine ≥ 1.6 mg/dL * Bilirubin ≥ 1.5 mg/dL * White blood cell (WBC) count \< 3 x 10\^9 /L * Platelets \< 100 x 10\^9/L * Hemoglobin \< 10 g/dL in females or \< 12g/dL in males * Glucose ≥ 200 mg/dL * Fasting blood sugar ≥ 126 mg/dL * Concurrent use of drugs listed in Appendix E of protocol
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Target Lesion Scoring Evaluated at Baseline and 4 Weeks | 4 weeks | Actual change in target lesion score comparing 4 week score with baseline score. Improvement is positive, worsening is negative. Target lesions scores range from 0 (no disease) to 12 (severe disease), and are scored based on the sum of erythema (0-4), induration (0-4) and scale (0-4) scores. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in the Target Lesion Visual Analog Scale (VAS) Score for Pruritus Evaluated at Baseline and 4 Weeks | 4 weeks | Visual Analog Scale (VAS) score for pruritus. Subjective measurement of pruritus on an analog scale with a single mark denoting self-perceived pruritus: Minimum 0mm for no itch, Maximum 100mm for worst itch imaginable. Scores are measured in millimeters. This secondary outcome is a percentage improvement from baseline score for pruritus. Improvement is negative, worsening is positive. |
| Safety Outcome Measures | 8 weeks | adverse events will be recorded and monitored. Adverse events will be noted in a separate chart. |
| Fluphenazine Serum Levels Measured at Baseline, 2 Hours Post Dose and 1 Week Post Dose. | 1 week | Number of participants with fluphenazine serum levels \> 0.200ng/ml, at baseline, 2 hours post dose and 1 week post dose. |
Countries
United States
Participant flow
Recruitment details
Recruitment from a dermatology clinic of a tertiary care medical center. Recruitment dates from Oct 2008 to Sep 2010.
Participants by arm
| Arm | Count |
|---|---|
| All Study Participants - Fluphenazine This will be an ascending dose study with the first cohort of 5 subjects dosed at 100 µg/mL, followed by cohorts at 500 and 2500 µg/mL. Dosing will be on Days 0, 7 and 14 and will consist of 5, or 10, 100 µL injections into the psoriatic lesion. The number of injections will depend on the lesion size. As this is a vehicle controlled study, subjects will receive intralesional injections of both drug and placebo, each into a separate target plaque, in a randomized fashion. | 15 |
| Total | 15 |
Baseline characteristics
| Characteristic | All Study Participants - Fluphenazine |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 1 Participants |
| Age, Categorical Between 18 and 65 years | 14 Participants |
| Age, Continuous | 51.5 years STANDARD_DEVIATION 12.5 |
| Region of Enrollment United States | 15 participants |
| Sex: Female, Male Female | 3 Participants |
| Sex: Female, Male Male | 12 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 12 / 15 |
| serious Total, serious adverse events | 0 / 15 |
Outcome results
Primary
Change in Target Lesion Scoring Evaluated at Baseline and 4 Weeks
Actual change in target lesion score comparing 4 week score with baseline score. Improvement is positive, worsening is negative. Target lesions scores range from 0 (no disease) to 12 (severe disease), and are scored based on the sum of erythema (0-4), induration (0-4) and scale (0-4) scores.
Time frame: 4 weeks
Population: All participants who successfully were enrolled.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change in Target Lesion Scoring Evaluated at Baseline and 4 Weeks | -1.4 units on a scale | Standard Deviation 1.5 |
| Fluphenazine | Change in Target Lesion Scoring Evaluated at Baseline and 4 Weeks | -1.4 units on a scale | Standard Deviation 1.8 |
Secondary
Change in the Target Lesion Visual Analog Scale (VAS) Score for Pruritus Evaluated at Baseline and 4 Weeks
Visual Analog Scale (VAS) score for pruritus. Subjective measurement of pruritus on an analog scale with a single mark denoting self-perceived pruritus: Minimum 0mm for no itch, Maximum 100mm for worst itch imaginable. Scores are measured in millimeters. This secondary outcome is a percentage improvement from baseline score for pruritus. Improvement is negative, worsening is positive.
Time frame: 4 weeks
Population: Participants who completed entire trial.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change in the Target Lesion Visual Analog Scale (VAS) Score for Pruritus Evaluated at Baseline and 4 Weeks | 0.86 percentage of baseline pruritus | Standard Deviation 15 |
| Fluphenazine | Change in the Target Lesion Visual Analog Scale (VAS) Score for Pruritus Evaluated at Baseline and 4 Weeks | -2.16 percentage of baseline pruritus | Standard Deviation 22.9 |
Secondary
Fluphenazine Serum Levels Measured at Baseline, 2 Hours Post Dose and 1 Week Post Dose.
Number of participants with fluphenazine serum levels \> 0.200ng/ml, at baseline, 2 hours post dose and 1 week post dose.
Time frame: 1 week
Population: All participants who were enrolled and completed baseline and week 1 were included.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Fluphenazine Serum Levels Measured at Baseline, 2 Hours Post Dose and 1 Week Post Dose. | 0 participants |
| Fluphenazine | Fluphenazine Serum Levels Measured at Baseline, 2 Hours Post Dose and 1 Week Post Dose. | 2 participants |
| 1 Week Post Dose | Fluphenazine Serum Levels Measured at Baseline, 2 Hours Post Dose and 1 Week Post Dose. | 2 participants |
Secondary
Safety Outcome Measures
adverse events will be recorded and monitored. Adverse events will be noted in a separate chart.
Time frame: 8 weeks
Population: All participants who completed enrollment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Safety Outcome Measures | 12 All Study Participant |