Safety and Efficacy of Combining nbUVB to Etanercept in Patients

Study Overview
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Brief Summary
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This study will provide data on the addition of narrow band ultra violet B (nbUVB) phototherapy to participants who have not shown an excellent response to three months of etanercept.

Detailed Description
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All participants will receive etanercept 50 mg twice a week for 12 weeks. Participants who reach PASI-90 at Day 84 will be discontinued from the study (they can continue receiving commercial etanercept outside the study). Participants remaining in the study at Day 84 will decrease etanercept to 50 mg weekly for another 12 weeks. Participants who do not attain a 90 percent reduction in PASI from baseline (PASI-90) after 12 weeks will be randomized (1:1) to receive either etanercept alone or etanercept with short courses of narrow band ultra violet B (nbUVB)phototherapy. Participants randomized to the nbUVB group will receive nbUVB treatments three times a weeks for at least four weeks. At every planned study visit after Day 84, nbUVB treatment will be discontinued in participants who reach PASI-90. nbUVB phototherapy will be re-initiated for another four weeks at the subsequent planned study visit if they lose their PASI-90 response. Efficacy will be evaluated with PASI, BSA and PGA by a blinded evaluator at Days 0, 28, 84, 112, 140 and 168. The effect of the treatment on quality of life will be evaluated using the DLQI questionnaire at Days 112, 140 and 168. Safety will be evaluated by physical examination and adverse events evaluation.

Official Title
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A Randomized Study Combining Etanercept and Short Courses of Narrow-Band UVB in Patients With Psoriasis Vulgaris

Conditions
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Psoriasis Vulgaris

Intervention / Treatment
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* Drug: Etanercept
* Device: nbUVB


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18 or older; Patient with moderate to severe plaque psoriasis for whom a decision to use etanercept has been made; At the investigator discretion, patient who would benefit from systemic therapy; PASI (psoriasis area and severity index) ≥ 10 and BSA (body surface area affected by psoriasis) ≥ 10 at day 0; Unless surgically sterile (or at least 1 year post-menopausal for women), abstinent or homosexual, patient (men and women) willing to use adequate contraceptive method for at least 30 days before Day 0 and until one month after the last drug administration; Patient capable of giving informed consent; Patient with normal or non clinically significant chest X ray within six months of screening; Patient with negative purified protein derivative (PPD) within 3 months of Day 0; Negative urine pregnancy test for women of childbearing potential Exclusion Criteria: Patient used topical steroid, topical tar preparations, or other anti-psoriatic preparations except tar or salicylic acid shampoo or hydrocortisone for the face, scalp, genital and inframammary areas within two weeks of Day 0; Patient with presence of erythrodermic, pustular or a predominantly guttate psoriasis; At the investigator's discretion, patient with any significant infection within 30 days of screening or a patient at risk of septicemia; Patient with evidence of any skin condition that would interfere with the evaluation of psoriasis; Patient used investigational drugs within 12 weeks or three half-life of Day 0 whichever is longer; Patient used systemic anti-psoriatic drugs such as steroids, retinoids, methotrexate, cyclosporine within four weeks of Day 0; Patient used any biologic such as alefacept, etanercept, efalizumab, infliximab and adalimumab within 12 weeks of Day 0; Patient used ultraviolet light therapy (UVB or nbUVB) within four weeks of Day 0 or PUVA (psoralen ultra violet A) within eight weeks of Day 0; Patient with prior or concurrent use of cyclophosphamide; Patient with concurrent sulfasalazine therapy or concurrent use of anakinra; Patient with an unstable or serious medical condition as defined by the investigator or presence of any significant medical condition that might cause this study to be detrimental to the patient. Uncontrolled or severe comorbidities such as diabetes mellitus requiring insulin; congestive heart failure (NYHA (New York Heart Association) class III or IV) or history of myocardial infarction or cerebrovascular accident or transient ischemic attack within three months of screening visit; unstable angina pectoris; uncontrolled hypertension, oxygen-dependent severe pulmonary disease; Patient with a known sero-positivity for HIV (human immunodeficiency virus) or history of any other immunosuppressing disease; Patient with active or chronic hepatitis B or C; Patient with any active or chronic infection within four weeks before screening or between the screening and baseline visits; Patient with any mycobacterial disease, patient with a positive PPD, a chest X-Ray suggestive of tuberculosis or patient taking anti-tuberculosis medication; Patient with a known hypersensitivity to etanercept or one of its components or known to have antibodies to etanercept; Patient who received a live attenuated vaccines within 12 weeks of Day 0 or plan to receive one during the study; Current pregnancy or lactation; At the investigator's discretion, patient with current or history of alcohol or drug abuse that would interfere with the ability of the patient to comply with the study protocol; Patient with systemic lupus erythematosus or demyelinating disorder (optic neuritis, multiple sclerosis or other); Patient with a history of cancer within five years of Day 0 or presence of cancer except for treated basal or squamous cell carcinoma and in situ cervix carcinoma; Patient who failed to respond to nbUVB in the past; Patient who have a contra-indication to nbUVB; Patient with latex sensitivity (applicable only if they are using prefilled syringe or prefilled SureClickTM autoinjector presentations); Patient with a history of non-compliance with other therapies.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Part 1 - Etanercept<br>All participants received etanercept 50 mg twice a week for 12 weeks. | Drug: Etanercept<br>* Etanercept 50 mg, subcutaneous (SC) injection.<br>* Other names: Enbrel;|
| Active Comparator: Part 2 - Etanercept and nbUVB<br>Participants who did not reach a 90 percent reduction in psoriasis area and severity index (PASI-90) after 12 weeks and were randomized to the narrow band ultra violet B (nbUVB) group. They received nbUVB treatments three times a week and 50 mg Etanercept once per week. | Drug: Etanercept<br>* Etanercept 50 mg, subcutaneous (SC) injection.<br>* Other names: Enbrel;Device: nbUVB<br> <br> * Other names: narrow band UVB;|
| Active Comparator: Part 2 - Etanercept<br>Participants who did not reach PASI-90 after 12 weeks and were randomized to the Etanercept group. They received 50 mg Etanercept once per a week. | Drug: Etanercept<br>* Etanercept 50 mg, subcutaneous (SC) injection.<br>* Other names: Enbrel;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants Attaining a 90 Percent Reduction in PASI From Baseline (PASI 90) - ITT | Four anatomic sites - head, upper extremities, trunk and lower extremities - are assessed for erythema, induration, and desquamation. The severity of each sign is assessed using a 5-point scale: 0 = No symptoms 1 = Slight 2 = Moderate 3 = Marked 4 = Very marked The area affected by psoriasis within a given anatomic site is estimated as a percentage of the total area of that anatomic site and assigned a numerical value according to the degree of psoriatic involvement from 0-6. Total scale 0 = best and 72 = worst | 112 and 140 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants Attaining a 75 Percent Reduction in PASI From Baseline (PASI 75) - ITT | Four anatomic sites - head, upper extremities, trunk and lower extremities - are assessed for erythema, induration, and desquamation. The severity of each sign is assessed using a 5-point scale: 0 = No symptoms 1 = Slight 2 = Moderate 3 = Marked 4 = Very marked The area affected by psoriasis within a given anatomic site is estimated as a percentage of the total area of that anatomic site and assigned a numerical value according to the degree of psoriatic involvement from 0-6. Total scale 0 = best and 72 = worst | 112, 140 and 168 days | 
| Number of Participants Attaining a 100% Reduction in PASI From Baseline (PASI 100) - ITT | Four anatomic sites - head, upper extremities, trunk and lower extremities - are assessed for erythema, induration, and desquamation. The severity of each sign is assessed using a 5-point scale: 0 = No symptoms 1 = Slight 2 = Moderate 3 = Marked 4 = Very marked The area affected by psoriasis within a given anatomic site is estimated as a percentage of the total area of that anatomic site and assigned a numerical value according to the degree of psoriatic involvement from 0-6. Total scale 0 = best and 72 = worst | 112, 140 and 168 days | 
| Number of Participants Attaining a 50% Reduction From Baseline in PASI From Baseline (PASI-50) - ITT | Four anatomic sites - head, upper extremities, trunk and lower extremities - are assessed for erythema, induration, and desquamation. The severity of each sign is assessed using a 5-point scale: 0 = No symptoms 1 = Slight 2 = Moderate 3 = Marked 4 = Very marked The area affected by psoriasis within a given anatomic site is estimated as a percentage of the total area of that anatomic site and assigned a numerical value according to the degree of psoriatic involvement from 0-6. Total scale 0 = best and 72 = worst | 28 and 84 days | 
| Number of Participants Attaining a 75 % Reduction in PASI From Baseline (PASI-75) - ITT | Four anatomic sites - head, upper extremities, trunk and lower extremities - are assessed for erythema, induration, and desquamation. The severity of each sign is assessed using a 5-point scale: 0 = No symptoms 1 = Slight 2 = Moderate 3 = Marked 4 = Very marked The area affected by psoriasis within a given anatomic site is estimated as a percentage of the total area of that anatomic site and assigned a numerical value according to the degree of psoriatic involvement from 0-6. Total scale 0 = best and 72 = worst | 28 and 84 days | 
| Number of Participants Attaining a 90 Percent Reduction in PASI From Baseline (PASI-90) - ITT | Four anatomic sites - head, upper extremities, trunk and lower extremities - are assessed for erythema, induration, and desquamation. The severity of each sign is assessed using a 5-point scale: 0 = No symptoms 1 = Slight 2 = Moderate 3 = Marked 4 = Very marked The area affected by psoriasis within a given anatomic site is estimated as a percentage of the total area of that anatomic site and assigned a numerical value according to the degree of psoriatic involvement from 0-6. Total scale 0 = best and 72 = worst | 28 and 84 days | 
| Number of Participants Attaining a 100 Percent Reduction in PASI From Baseline (PASI-100) - ITT | Four anatomic sites - head, upper extremities, trunk and lower extremities - are assessed for erythema, induration, and desquamation. The severity of each sign is assessed using a 5-point scale: 0 = No symptoms 1 = Slight 2 = Moderate 3 = Marked 4 = Very marked The area affected by psoriasis within a given anatomic site is estimated as a percentage of the total area of that anatomic site and assigned a numerical value according to the degree of psoriatic involvement from 0-6. Total scale 0 = best and 72 = worst | 28 and 84 days | 
| Number of Patients Attaining a PGA (Physician's Global Assessment) of 0 or 1 - ITT | Number of patients attaining a Physician's Global Assessment (PGA) of clear (0) or minimal (1). PGA scores are evaluated at each time point. The degree of overall lesion severity at the time of the physician's evaluation of the patient evaluated using the following scale: 0 = clear 1 = minimal 2 = mild 3 = moderate 4 = severe 5 = very severe The scale evaluates plaque elevation, scaling and erythema. | 0, 112, 140 and 168 days | 
| Body Surface Area (BSA) Affected by Psoriasis - ITT | BSA scores are evaluated at each time point. BSA is a measure of the percentage of body surface affected by psoriasis. | 0, 84, 112, 140 and 168 days | 
| Dermatology Life Quality Index (DLQI) - ITT | The aim of this questionnaire is to measure how much one's skin problem has affected one's life over the week prior to the visit. Questionnaire is patient-assessed (self-reported). DLQI scores are evaluated at each time point. Scale is from 0 best to 30 worst. 0-1 = no effect at all on patient's life 2-5 = small effect on patient's life 6-10 = moderate effect on patient's life 11-20 = very large effect on patient's life 21-30 = extremely large effect on patient's life | 0, 84, 112, 140 and 168 days | 
| Number of Adverse Drug Reactions - ITT | Evaluation of safety of etanercept and nbUVB as compared to etanercept alone by reporting the incidence rates of adverse drug reactions. Definition: A response to a drug that is noxious and unintended and that occurs at doses normally used in man for prophylaxis, diagnosis, or therapy of diseases or for modification of physiological function. Only adverse drug reactions that were at least possibly related to etanercept were recorded. All symptoms observed at the injection site such as erythema, burning, edema and pruritus were recorded together as Injection Site Reaction. | 196 days | 
| Number of Infectious Adverse Events - ITT | Evaluation of safety of etanercept and nbUVB as compared to etanercept alone by reporting the incidence rates of infectious adverse events. Definition: An adverse event is any untoward medical occurrence in a patient administered a pharmaceutical product, without regard to the possibility of a causal relationship with this treatment. Only infectious and malignant (including any type of skin cancer) adverse events were recorded. | 196 days | 
| Number of Serious Adverse Events - ITT | Evaluation of safety of etanercept and nbUVB as compared to etanercept alone by reporting the incidence rates of serious adverse events. Definition: any adverse event from this study that results in one of the following outcomes, or is significant for any other reason: death initial or prolonged inpatient hospitalization a life-threatening experience (that is, immediate risk of dying) persistent or significant disability/incapacity congenital anomaly/birth defect | 196 days | 
| Number of Participants Attaining a 90 Percent Reduction in PASI From Baseline (PASI 90) - PP | Four anatomic sites - head, upper extremities, trunk and lower extremities - are assessed for erythema, induration, and desquamation. The severity of each sign is assessed using a 5-point scale: 0 = No symptoms 1 = Slight 2 = Moderate 3 = Marked 4 = Very marked The area affected by psoriasis within a given anatomic site is estimated as a percentage of the total area of that anatomic site and assigned a numerical value according to the degree of psoriatic involvement from 0-6. Total scale 0 = best and 72 = worst | 84, 112, 140 and 168 days | 
| Number of Participants Attaining a 75 Percent Reductionin PASI From Baseline (PASI-75) - PP | Four anatomic sites - head, upper extremities, trunk and lower extremities - are assessed for erythema, induration, and desquamation. The severity of each sign is assessed using a 5-point scale: 0 = No symptoms 1 = Slight 2 = Moderate 3 = Marked 4 = Very marked The area affected by psoriasis within a given anatomic site is estimated as a percentage of the total area of that anatomic site and assigned a numerical value according to the degree of psoriatic involvement from 0-6. Total scale 0 = best and 72 = worst | 84, 112, 140 and 168 days | 
| Number of Participants Attaining a 100 Percent Reduction in PASI From Baseline (PASI-100) - PP | Four anatomic sites - head, upper extremities, trunk and lower extremities - are assessed for erythema, induration, and desquamation. The severity of each sign is assessed using a 5-point scale: 0 = No symptoms 1 = Slight 2 = Moderate 3 = Marked 4 = Very marked The area affected by psoriasis within a given anatomic site is estimated as a percentage of the total area of that anatomic site and assigned a numerical value according to the degree of psoriatic involvement from 0-6. Total scale 0 = best and 72 = worst | 84, 112, 140 and 168 days | 
| Number of Patients Attaining a PGA (Physician's Global Assessment) of 0 or 1 - PP | Number of patients attaining a Physician's Global Assessment (PGA) of clear (0) or minimal (1). PGA scores are evaluated at each time point. The degree of overall lesion severity at the time of the physician's evaluation of the patient evaluated using the following scale: 0 = clear 1 = minimal 2 = mild 3 = moderate 4 = severe 5 = very severe The scale evaluates plaque elevation, scaling and erythema. | 84, 112, 140 and 168 days | 
| Body Surface Area (BSA) Affected by Psoriasis - PP | BSA scores are evaluated at each time point. BSA is a measure of the percentage of body surface affected by psoriasis. | 0, 84, 112, 140 and 168 days | 
| Dermatology Life Quality Index (DLQI) - PP | The aim of this questionnaire is to measure how much one's skin problem has affected one's life over the week prior to the visit. Questionnaire is patient-assessed (self-reported). DLQI scores are evaluated at each time point. Scale is from 0 best to 30 worst. 0-1 = no effect at all on patient's life 2-5 = small effect on patient's life 6-10 = moderate effect on patient's life 11-20 = very large effect on patient's life 21-30 = extremely large effect on patient's life | 0, 84, 112, 140 and 168 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Etanercept, UVB, Enbrel, Psoriasis.