Adalimumab in Combination With Topical Treatment (Calcipotriol/Betamethasone) in Subjects With Moderate to Severe Psoriasis and Insufficient Response to Classic Systemic Treatment

Study Overview
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Brief Summary
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The objective of this study is to assess the efficacy and safety of adalimumab in combination with topical psoriasis treatment, calcipotriol/betamethasone, vs. adalimumab in combination with matching vehicle in subjects with moderate to severe chronic plaque psoriasis.

Detailed Description
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Additional information regarding sponsors: Abbott GmbH & Co. KG is sponsor for EU member states. Abbott US is sponsor for non-EU member states.

Official Title
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A Multi-center, Randomized, Vehicle-Controlled Study to Assess the Efficacy and Safety of Adalimumab in Combination With Topical Treatment (Calcipotriol/Betamethasone) in Subjects With Moderate to Severe Psoriasis and Insufficient Response to Classic Systemic Treatment (BELIEVE)

Conditions
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Chronic Plaque Psoriasis

Intervention / Treatment
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* Biological: adalimumab
* Drug: Calcipotriol/Betamethasone Ointment
* Drug: placebo (vehicle ointment)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject is >= 18 years of age Subject had a clinical diagnosis of chronic plaque psoriasis for at least 6 months, and has moderate to severe plaque psoriasis Subject must have been treated and failed to respond to, or has a contraindication to, or is intolerant to at least two different systemic therapies, one of which must be cyclosporine, or methotrexate or oral PUVA Subject is judged to be in generally good health as determined by the principal investigator Exclusion Criteria: Subject has previous exposure to adalimumab Subject cannot discontinue systemic therapies and/or topical therapies for the treatment of psoriasis and cannot avoid UVB or PUVA phototherapy Subject is taking or requires oral or injectible corticosteroids Subject diagnosed with erythrodermic psoriasis, pustular psoriasis, medication-induced or medication-exacerbated psoriasis or new onset guttate psoriasis Subject considered by the investigator, for any reason, to be an unsuitable candidate Female subject who is pregnant or breast-feeding or considering becoming pregnant Subject has a calcium metabolism disorder

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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: adalimumab + placebo<br>adalimumab + placebo (vehicle ointment) | Biological: adalimumab<br>* subcutaneous injection using prefilled pen/syringe, solution containing 40 mg in 0.8 milliliters; 2 injections given at Baseline (Day 1) then once every other week from Weeks 1 though 15<br>* Other names: Humira;Drug: placebo (vehicle ointment)<br>* Topical vehicle ointment (matching active calcipotriol/betamethasone ointment) to be applied once daily to affected psoriasis skin on trunk and extremities for first 4 weeks and as needed from Week 5 through Week 16<br>|
| Active Comparator: adalimumab + calcipotriol/betamethasone<br>adalimumab + calcipotriol/betamethasone ointment | Biological: adalimumab<br>* subcutaneous injection using prefilled pen/syringe, solution containing 40 mg in 0.8 milliliters; 2 injections given at Baseline (Day 1) then once every other week from Weeks 1 though 15<br>* Other names: Humira;Drug: Calcipotriol/Betamethasone Ointment<br>* Topical ointment (calcipotriol 50 mcg/g and betamethasone 500 mcg/g) to be applied once daily to affected psoriasis skin on trunk and extremities for first 4 weeks and as needed from Week 5 through Week 16<br>* Other names: Daivobet;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Who Achieve a PASI75 Response at Week 16 Compared With Baseline (Week 0) | PASI75 is defined as at least a 75% reduction in PASI (Psoriasis Area and Severity Index) score compared with the Baseline PASI score. PASI scores range from 0.0 (best) to 72.0 (worst), with the highest score representing complete erythroderma of the severest degree. The percent decrease in score is calculated as (Week 0 PASI score minus Week 16 PASI score) divided by Week 0 PASI score. Positive percent decreases indicate improvement, with best improvement being 100%. The outcome measure is the percentage of participants who had at least a 75% PASI score decrease. | Week 0 and Week 16 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With a PASI50 Response at Week 16 Compared With Baseline (Week 0) | PASI50 is defined as at least a 50% reduction in PASI (Psoriasis Area and Severity Index) score compared with the Baseline PASI score. PASI scores range from 0.0 (best) to 72.0 (worst), with the highest score representing complete erythroderma of the severest degree. The percent decrease in score is calculated as (Week 0 PASI score minus Week 16 PASI score) divided by Week 0 PASI score. Positive percent decreases indicate improvement, with best improvement 100%. The outcome measure is the percentage of participants who had at least a 50% PASI score decrease. | Week 0 and Week 16 | 
| Percentage of Participants With a PASI90 Response at Week 16 Compared With Baseline (Week 0) | PASI90 is defined as at least a 90% reduction in PASI (Psoriasis Area and Severity Index) score compared with the Baseline PASI score. PASI scores range from 0.0 (best) to 72.0 (worst), with the highest score representing complete erythroderma of the severest degree. The percent decrease in score is calculated as (Week 0 PASI score minus Week 16 PASI score) divided by Week 0 PASI score. Positive percent decreases indicate improvement, with best improvement 100%. The outcome measure is the percentage of participants who had at least a 90% PASI score decrease. | Week 0 and Week 16 | 
| Percentage of Participants With a PASI100 Response at Week 16 Compared With Baseline (Week 0) | PASI100 is defined as at least a 100% reduction in PASI (Psoriasis Area and Severity Index) score compared with the Baseline PASI score. PASI scores range from 0.0 (best) to 72.0 (worst) with the highest score representing complete erythroderma of the severest degree. The percent decrease in score is calculated as (Week 0 PASI score minus Week 16 PASI score) divided by Week 0 PASI score. Positive percent decreases indicate improvement, with best improvement 100%. The outcome measure is the percentage of participants who had at least a 100% PASI score decrease. | Week 0 and Week 16 | 
| Percentage of Participants Achieving a Physician's Global Assessment (PGA) of Clear or Minimal at Week 2 | PGA is a physician's assessment of severity of disease (grading lesion severity). PGA scores range from 0 (best) to 6 (worst): on the 6-point scale, a score of 0 = Clear and a score of 6 = Very Severe for the lesion severity. PGA Clear (0) is no plaque elevation over normal skin and no scale with or without erythema. Minimal (1) is possible plaque elevation but difficult to ascertain a slight elevation above normal skin. Percentage of participants: 0% to 100% (best). | Week 2 | 
| Percentage of Participants Achieving a Physician's Global Assessment (PGA) of Clear or Minimal at Week 4 | PGA is a physician's assessment of severity of disease (grading lesion severity). PGA scores range from 0 (best) to 6 (worst): on the 6-point scale, a score of 0 = Clear and a score of 6 = Very Severe for the lesion severity. PGA Clear (0) is no plaque elevation over normal skin and no scale with or without erythema. Minimal (1) is possible plaque elevation but difficult to ascertain a slight elevation above normal skin. Percentage of participants: 0% to 100% (best). | Week 4 | 
| Percentage of Participants Achieving a Physician's Global Assessment (PGA) of Clear or Minimal at Week 8 | PGA is a physician's assessment of severity of disease (grading lesion severity). PGA scores range from 0 (best) to 6 (worst): on the 6-point scale, a score of 0 = Clear and a score of 6 = Very Severe for the lesion severity. PGA Clear (0) is no plaque elevation over normal skin and no scale with or without erythema. Minimal (1) is possible plaque elevation but difficult to ascertain a slight elevation above normal skin. Percentage of participants: 0% to 100% (best). | Week 8 | 
| Percentage of Participants Achieving a Physician's Global Assessment (PGA) of Clear or Minimal at Week 12 | PGA is a physician's assessment of severity of disease (grading lesion severity). PGA scores range from 0 (best) to 6 (worst): on the 6-point scale, a score of 0 = Clear and a score of 6 = Very Severe for the lesion severity. PGA Clear (0) is no plaque elevation over normal skin and no scale with or without erythema. Minimal (1) is possible plaque elevation but difficult to ascertain a slight elevation above normal skin. Percentage of participants: 0% to 100% (best). | Week 12 | 
| Percentage of Participants Achieving a Physicians Global Assessment (PGA) Response of Clear or Minimal at Week 16 | PGA is a physician's assessment of severity of disease (grading lesion severity). PGA scores range from 0 (best) to 6 (worst): on the 6-point scale, a score of 0 = Clear and a score of 6 = Very Severe for the lesion severity. PGA Clear (0) is no plaque elevation over normal skin and no scale with or without erythema. Minimal (1) is possible plaque elevation but difficult to ascertain a slight elevation above normal skin. Percentage of participants: 0% to 100% (best). | Week 16 | 
| Percent Change From Baseline in the Dermatology Life Quality Index (DLQI) Total Score at Week 16 Compared With Baseline (Week 0) | DLQI is a participant-reported outcome consisting of a set of 10 questions regarding the degree to which (i.e., how much) the subject's skin has affected certain behaviors and quality of life over the last week. Responses to each are: very much, a lot, a little, or not at all. Total score range: 0 (best) to 30 (worst). Negative change and percent change from Baseline indicate improvement, with best improvement -100%. | Week 0 and Week 16 | 
| Percent Change in the Dermatology Life Quality Index (DLQI) Total Score at Week 2 Compared With Baseline (Week 0) | DLQI is a participant-reported outcome consisting of a set of 10 questions regarding the degree to which (i.e., how much) the subject's skin has affected certain behaviors and quality of life over the last week. Responses to each are: very much, a lot, a little, or not at all. Total score range: 0 (best) to 30 (worst). Negative change and percent change from Baseline indicate improvement, with best improvement -100%. | Week 0 and Week 2 | 
| Percent Change From Baseline in the Dermatology Life Quality Index (DLQI) Total Score at Week 4 Compared With Baseline (Week 0) | DLQI is a participant-reported outcome consisting of a set of 10 questions regarding the degree to which (i.e., how much) the subject's skin has affected certain behaviors and quality of life over the last week. Responses to each are: very much, a lot, a little, or not at all. Total score range: 0 (best) to 30 (worst). Negative change and percent change from Baseline indicate improvement, with best improvement -100%. | Week 0 and Week 4 | 
| Percent Change From Baseline in the Dermatology Life Quality Index (DLQI) Total Score at Week 8 Compared With Baseline (Week 0) | DLQI is a participant-reported outcome consisting of a set of 10 questions regarding the degree to which (i.e., how much) the subject's skin has affected certain behaviors and quality of life over the last week. Responses to each are: very much, a lot, a little, or not at all. Total score range: 0 (best) to 30 (worst). Negative change and percent change from Baseline indicate improvement, with best improvement -100%. | Week 0 and Week 8 | 
| Percent Change From Baseline in the Dermatology Life Quality Index (DLQI) Total Score at Week 12 Compared With Baseline (Week 0) | DLQI is a participant-reported outcome consisting of a set of 10 questions regarding the degree to which (i.e., how much) the subject's skin has affected certain behaviors and quality of life over the last week. Responses to each are: very much, a lot, a little, or not at all. Total score range: 0 (best) to 30 (worst). Negative change and percent change from Baseline indicate improvement, with best improvement -100%. | Week 0 and Week 12 | 
| Percent Change in Short Form 36 Health Survey (SF-36) Physical Component Score (PCS) at Week 16 Compared With Baseline (Week 0) | Short Form 36 Health Survey (SF-36) Physical Component Score (PCS) is a participant-reported outcome that employs a questionnaire that asks for the participant's views about their health. Percent change at Week 16 is calculated as (Week 16 SF-36 PCS minus Week 0 SF-36 PCS) divided by Week 0 SF-36 PCS. Positive percent change in score indicates improvement, with best improvement 100%. | Week 0 and Week 16 | 
| Percent Change in Short Form 36 Health Survey (SF-36) Physical Component Score (PCS) at Week 8 Compared With Baseline (Week 0) | Short Form 36 Health Survey (SF-36) Physical Component Score (PCS) is a participant-reported outcome that employs a questionnaire that asks for the participant's views about their health. Percent change at Week 8 is calculated as (Week 8 SF-36 PCS minus Week 0 SF-36 PCS) divided by Week 0 SF-36 PCS. Positive percent change in score indicates improvement, with best improvement 100%. | Week 0 and Week 8 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Psoriasis, Moderate Psoriasis, Severe Psoriasis, Chronic Plaque Psoriasis, Severe Chronic Plaque Psoriasis