Safety and Efficacy Study of Combination Treatment With Excimer Laser, Clobex Spray, and Vectical Ointment in the Treatment of Psoriasis
|First Received Date ICMJE||November 10, 2009|
|Last Updated Date||April 24, 2014|
|Start Date ICMJE||June 2010|
|Estimated Primary Completion Date||December 2014 (final data collection date for primary outcome measure)|
|Current Primary Outcome Measures ICMJE
||The primary endpoint will be the percentage of patients achieving PASI-75 response at week 12. [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]|
|Original Primary Outcome Measures ICMJE||Same as current|
|Change History||Complete list of historical versions of study NCT01012713 on ClinicalTrials.gov Archive Site|
|Current Secondary Outcome Measures ICMJE
|Original Secondary Outcome Measures ICMJE||Same as current|
|Current Other Outcome Measures ICMJE||Not Provided|
|Original Other Outcome Measures ICMJE||Not Provided|
|Brief Title ICMJE||Safety and Efficacy Study of Combination Treatment With Excimer Laser, Clobex Spray, and Vectical Ointment in the Treatment of Psoriasis|
|Official Title ICMJE||Pilot Open-Label Clinical Trial to Test Efficacy and Safety of Combination of Clobex® Spray With Excimer Laser Therapy [Photomedex XTRAC ® Velocity] in the Treatment of Generalized Plaque Psoriasis Followed by Maintenance With Topical Vectical® Ointment|
This is a 12-week, open-label, pilot trial evaluating the efficacy and safety of the combination of Clobex® spray with excimer laser therapy as the initial treatment of generalized plaque psoriasis, followed by maintenance therapy with topical Vectical. The study will be conducted in three distinct periods, namely Period A, Period B, and Period C, each of 4 weeks duration. During Period A (weeks 1 through 4), patients will use Clobex® spray twice daily along with excimer laser treatments twice weekly with the Photomedex XTRAC® Velocity machine. The goal of Period A is to achieve Psoriasis Area Severity Index (PASI) 75 in 100% of patients within four weeks. During Period B (weeks 5 through 8), patients would be treated with topical Vectical® twice daily. Thus, there is a steroid-free interval during which patients will not be using Clobex® spray. The goal of Period B is to maintain the patient's response using only non-steroid options. During Period C of the study, patients will use Clobex® spray BID and Vectical® BID. Period C (weeks 9 through 12) will be a "booster" period in which the goal is to see if 100% of patients can achieve Psoriasis Area Severity Index (PASI) 90-100. Regarding excimer laser therapy: all patients will be receiving excimer laser therapy twice weekly for the first 6 weeks of the study (up to the halfway point) which is 12 excimer laser treatments. At that point, only those patients achieving <Psoriasis Area Severity Index (PASI)75 response will continue to receive twice weekly excimer laser treatments for the remaining 6 weeks of the study.
Psoriasis is an inflammatory skin disease affecting approximately 2% of the population, and approximately one-third of patients experience generalized psoriasis ( ). Current treatment options include topical medications, ultraviolet B and oral psoralen with ultraviolet A phototherapy, biologic agents, non-biologic systemic medications, and combinations of the aforementioned. Phototherapy treatment, although effective for many patients, often is inconvenient, requiring three treatments weekly for 2-3 months in order to achieve significant improvement in a patient's psoriasis. The newer biologic medications, while effective in many patients, work by systemic immunosuppression with increased risk of malignancies, infections including tuberculosis and histoplasmosis, congestive heart failure, lupus-like syndrome, demyelinating diseases, etc. In addition to side effects from systemic immunosuppression, non-biologic systemic agents can have major organ toxicity as a potential side effect including bone marrow suppression, liver toxicity, kidney toxicity, etc.
Currently, we are at the threshold of a new era, where the possibility exists of treating generalized psoriasis with absolute systemic safety and better efficacy than any systemic or biologic agent. This possibility can only become a reality with a "perfect storm," in which three storms collide. This "perfect storm" may achieve a result which no other therapy has yet achieved: a Psoriasis Area Severity Index (PASI)75 response in 100% of patients after only 4 weeks of therapy. The three "storms" include Clobex® spray, Vectical® ointment, and the excimer laser machine XTRAC® Velocity.
Laser therapy (fiberoptically-directed monochromatic UVB light) targets only psoriatic plaques. This allows much more aggressive phototherapy as compared to traditional ultraviolet B and oral psoralen with ultraviolet A , which exposes non-involved skin as well as psoriatic skin to UV light. With aggressive excimer laser therapy, it is well known that psoriasis can improve significantly or clear in approximately ten sessions instead of the 30 to 40 sessions needed with regular full-body phototherapy to achieve clearance of the skin. This dramatic difference is attributed to the fact that psoriatic lesions are able to withstand a much higher dose of light than non-involved skin. Excimer laser therapy dosing is determined by the maximum tolerance of psoriatic skin whereas full body UV therapy dosing is determined by the MED (minimal erythema dose) of non-involved skin. Delivery of higher doses subsequently results in faster clinical response and much greater clinical efficacy. Hence, the new supra-erythemogenic phototherapy strategy results in a fewer number of sessions needed for clearance ( ). The supra-erythemogenic phototherapy strategy involves delivering UVB at a dose much greater than the minimal erythema dose (MED) (2). MED is the traditional limit on how aggressively non-laser phototherapy can be conducted (UVB doses beyond the MED will burn the patient).
In addition, excimer laser therapy results in no photo-damage to non-involved skin, given its targeted application. The Photomedex XTRAC® Velocity is the latest version of the excimer laser, which is 300-400% more powerful than its predecessor, the XTRAC® Ultra machine. This increased power makes treatment of generalized, moderate to severe psoriasis not only feasible but attractive. Time required for each treatment is decreased by one-third, as compared to the XTRAC® Ultra which was previously the most powerful excimer laser machine. XTRAC® Velocity is not yet available: it is scheduled to be introduced in a few months. With XTRAC® Velocity, it is expected that generalized psoriasis patients with 10-30% total body surface involvement can be treated in 10-15 minutes and great improvement can be achieved after approximately just ten laser treatment sessions.
Using the XTRAC® Ultra machine, in a pilot study of 9 patients receiving excimer laser therapy twice weekly for 12 weeks, 77% of patients achieved a Psoriasis Area Severity Index (PASI) 75 response ( ). In another study of 124 patients with stable plaque psoriasis (n = 124) covering less than 10% body surface area (BSA) were enrolled and 80 completed the study ( ). Seventy-two percent of patients achieved at least 75% clearing in an average of 6.2 treatments. Thirty-five percent achieved 90% clearing in an average of 7.5 treatments. In another study of 40 patients treated with the excimer laser under a protocol determined by MED of the involved skin, patients cleared in approximately half the number of treatments compared to patients treated under a protocol where dosage was determined by MED of non-involved skin ( ). However, aggressive laser therapy can also irritate the skin, and Clobex® spray can be an ideal partner to enhance the efficacy and prevent irritation of the skin from aggressive, supra-erythemogenic UVB irradiation. Moreover, beyond prevention of skin irritation, there are additional merits of combining Clobex® spray with excimer laser. These are the following:
In a study of 1254 subjects treated with clobetasol propionate spray 0.05% as monotherapy twice daily for four weeks, 35.7% of patients achieved clearance and 37.3% of patients were almost clear using a 6-point target plaque severity scale. Additionally, at week 4, 80% of subjects achieved target plaque severity (TPS) success, p<0.001. This was specifically defined as a score of clear, almost clear using the TPS scale or an improvement in severity of 2 grades. Topical steroids have the potential for adrenal suppression. However, when topical steroids are used for one month or less at a time, this transient adrenal suppression that may result is not a clinical problem.Furthermore, when using Clobex® spray, patients are required to have a steroid-free interval after 4 weeks of therapy. The effect of Clobex® spray can be maintained with a safe, non-steroidal topical medication, such as Vectical. This newer Vitamin D topical agent can be used up to 210 g weekly, as compared to topical calcipotriol (Dovonex®) which is limited to 100 g weekly, due to the better safety profile of Vectical. Thus, Vectical can be used for patients with generalized plaque psoriasis covering up to 35% body surface area. In addition, a comparative study in 250 patients demonstrated that Vectical caused significantly less skin irritation as compared to calcipotriol ( ). Thus, with the imminent approval of Vectical, we are entering a new era where a Vitamin D analogue can be used to treat patients with generalized psoriasis. With these three "storms" gathering force, we propose the following study.
|Study Type ICMJE||Interventional|
|Study Phase||Phase 4|
|Study Design ICMJE||Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Condition ICMJE||Chronic Stable Plaque Psoriasis|
|Study Arm (s)||Experimental: Open-Label Treatment
All patients will receive treatment with Clobex Spray, Vectical Ointment, and Excimer Laser
|Publications *||Not Provided|
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
|Recruitment Status ICMJE||Recruiting|
|Estimated Enrollment ICMJE||30|
|Estimated Completion Date||December 2014|
|Estimated Primary Completion Date||December 2014 (final data collection date for primary outcome measure)|
|Eligibility Criteria ICMJE||
|Ages||18 Years and older|
|Accepts Healthy Volunteers||No|
|Listed Location Countries ICMJE||United States|
|Removed Location Countries|
|NCT Number ICMJE||NCT01012713|
|Other Study ID Numbers ICMJE||Perfect Storm|
|Has Data Monitoring Committee||No|
|Responsible Party||University of California, San Francisco|
|Study Sponsor ICMJE||University of California, San Francisco|
|Collaborators ICMJE||Not Provided|
|Information Provided By||University of California, San Francisco|
|Verification Date||April 2014|
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP