Study to Investigate Efficacy and Safety of Adalimumab in Japanese Subjects With Generalized Pustular Psoriasis (GPP)

Study Overview
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Brief Summary
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The purpose of this study was to investigate the efficacy, safety, and pharmacokinetics of adalimumab in Japanese participants with generalized pustular psoriasis (GPP) who did not have an adequate response to their currently approved treatment.

Detailed Description
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This was a Phase 3, multicenter, open-label, single-arm study of adalimumab in Japanese participants with generalized pustular psoriasis (GPP). The study included a 30-day screening period, a 52-week treatment period, and a 70-day follow-up period. The dose regimen of adalimumab used in this study was 80 mg at Week 0 by subcutaneous (SC) injection, followed by 40 mg every other week (eow) on and after Week 2 until Week 50. Dose escalation to 80 mg eow was allowed for participants who did not have adequate response on or after Week 8.

Official Title
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A Multicenter, Open-Label Study of Adalimumab in Japanese Subjects With Generalized Pustular Psoriasis

Conditions
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Adalimumab, Generalized Pustular Psoriasis (GPP), Japanese

Intervention / Treatment
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* Drug: Adalimumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of generalized pustular psoriasis Total skin score of at least 3 and erythema with pustules (skin score of at least 1) at baseline in the Japan Dermatology Association (JDA) severity index of Generalized Pustular Psoriasis (GPP) in GPP Medical Care Guideline 2014 in Japan Inadequate response to, or intolerance to, or contraindication to the currently approved GPP treatment (excluding infliximab) Infliximab secondary failure, or intolerant to infliximab Exclusion Criteria: Erythrodermic psoriasis, guttate psoriasis or sub-corneal pustular dermatosis at Screening Drug-induced GPP Cannot stop ongoing use of prohibited GPP treatments Total JDA severity index of GPP of 14 or more in GPP Medical Care Guideline 2014 in Japan

Ages Eligible for Study
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Minimum Age: 15 Years
Maximum Age: 75 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Participants receiving adalimumab<br>80 mg at Week 0 by subcutaneous (SC) injection, followed by 40 mg every other week (eow) on and after Week 2 until Week 50. Dose escalation to 80 mg eow was allowed for participants who did not have adequate response on or after Week 8. | Drug: Adalimumab<br>* Adalimumab pre-filled syringe, administered by subcutaneous injection<br>* Other names: ABT-D2E7;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of Participants Achieving Clinical Response at Week 16 | Clinical Response was defined as reduction of the Generalized Pustular Psoriasis (GPP) total skin score (range 0-9, with 9 representing severe symptoms) relative to baseline (Day 1), according to Japan Dermatology Association (JDA) severity index in GPP medical care guideline 2014. The total skin score is the combined skin scores for area of erythema (redness), area of erythema with pustules (small pockets of pus), and area of edema (swelling). Clinical Response was defined as the improvement (reduction) of total skin score of at least 1 point (if the participant's baseline total skin score was 3); improvement (reduction) at least 2 points (if the participant's baseline total skin score was 4-9); or remission if the total skin score was 0. | Baseline and Week 16 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants Achieving Clinical Response Over Time | Clinical Response was defined as reduction of the Generalized Pustular Psoriasis (GPP) total skin score (range 0-9, with 9 representing severe symptoms) relative to baseline (Day 1), according to Japan Dermatology Association (JDA) severity index in GPP medical care guideline 2014. The total skin score is the combined skin scores for area of erythema (redness), area of erythema with pustules (small pockets of pus), and area of edema (swelling). Clinical Response was defined as the improvement (reduction) of total skin score of at least 1 point (if the participant's baseline total skin score was 3); improvement (reduction) at least 2 points (if the participant's baseline total skin score was 4-9); or remission if the total skin score was 0. | Baseline, Week 2, Week 4, Week 8, Week 12, Week 24, Week 36, Week 52 | 
| Number of Participants Achieving Clinical Remission Over Time | The Generalized Pustular Psoriasis (GPP) total skin score (range 0-9, with 9 representing severe symptoms) was calculated according to Japan Dermatology Association (JDA) severity index in GPP medical care guideline 2014. The total skin score is the combined skin scores for area of erythema (redness), area of erythema with pustules (small pockets of pus), and area of edema (swelling). Clinical remission was defined as a total skin score of 0. | Week 2, Week 4, Week 8, Week 12, Week 16, Week 24, Week 36, Week 52 | 
| Mean Change From Baseline in the Total GPP Score Over Time | The Generalized Pustular Psoriasis (GPP) total score (range 0-17, with 17 representing severe disease) was calculated according to Japan Dermatology Association (JDA) severity index in GPP medical care guideline 2014. The total skin score (range 0-9, with 9 representing severe symptoms) is the combined skin scores for area of erythema (redness), area of erythema with pustules (small pockets of pus), and area of edema (swelling). The systemic and laboratory results score ([range 0-8, with 8 representing severe disease] assesses body temperature, white blood cell [WBC] count, high-sensitivity C-reactive protein [hs-CRP], and serum albumin). Negative values indicate improvement from baseline. | Baseline, Week 2, Week 4, Week 8, Week 12, Week 16, Week 24, Week 36, Week 52 | 
| Mean Change From Baseline in JDA Severity Index of GPP Over Time | The Generalized Pustular Psoriasis (GPP) total score (range 0-17, with 17 representing severe disease) was calculated according to Japan Dermatology Association (JDA) severity index in GPP medical care guideline 2014. The total skin score (range 0-9, with 9 representing severe symptoms) is the combined skin scores for area of erythema (redness), area of erythema with pustules (small pockets of pus), and area of edema (swelling). The systemic and laboratory results score ([range 0-8, with 8 representing severe disease] assesses body temperature, white blood cell [WBC] count, high-sensitivity C-reactive protein [hs-CRP], and serum albumin). A total score on the JDA severity index of 0-6 is categorized as Mild, Moderate is 7-10, and Severe is 11-17. | Baseline, Week 2, Week 4, Week 8, Week 12, Week 16, Week 24, Week 36, Week 52 | 
| Mean Change From Baseline in Total Skin Score Over Time | The Generalized Pustular Psoriasis (GPP) total skin score (range 0-9, with 9 representing severe symptoms) was calculated according to Japan Dermatology Association (JDA) severity index in GPP medical care guideline 2014. The total skin score is the combined skin scores for area of erythema (redness), area of erythema with pustules (small pockets of pus), and area of edema (swelling). Negative values indicate improvement from baseline. | Baseline, Week 2, Week 4, Week 8, Week 12, Week 16, Week 24, Week 36, Week 52 | 
| Mean Percent Change From Baseline in Total Skin Score Over Time | The Generalized Pustular Psoriasis (GPP) total skin score (range 0-9, with 9 representing severe symptoms) was calculated according to Japan Dermatology Association (JDA) severity index in GPP medical care guideline 2014. The total skin score is the combined skin scores for area of erythema (redness), area of erythema with pustules (small pockets of pus), and area of edema (swelling). Negative values indicate improvement from baseline. | Baseline, Week 2, Week 4, Week 8, Week 12, Week 16, Week 24, Week 36, Week 52 | 
| Mean Change From Baseline in Total Systemic/Laboratory Test Score Over Time | The Generalized Pustular Psoriasis (GPP) total systemic/laboratory test score ([range 0-8, with 8 representing severe disease] assesses body temperature, white blood cell [WBC] count, high-sensitivity C-reactive protein [hs-CRP], and serum albumin). Negative values indicate improvement from baseline. | Baseline, Week 2, Week 4, Week 8, Week 12, Week 16, Week 24, Week 36, Week 52 | 
| Mean Change From Baseline in Total Erythema Area Over Time | The Generalized Pustular Psoriasis (GPP) skin score scores for the total area of erythema (redness) were calculated according to Japan Dermatology Association (JDA) severity index in GPP medical care guideline 2014. The total erythema area is evaluated on a scale of 0 (none) to 3 (severe), with the percentage of body surface area involvement defined as follows: severe ≥ 75%; moderate, ≥ 25% and < 75%; mild, < 25%); and none (0%). Negative values indicate improvement from baseline. | Baseline, Week 2, Week 4, Week 8, Week 12, Week 16, Week 24, Week 36, Week 52 | 
| Mean Change From Baseline in Total Erythema Area With Pustules Over Time | The Generalized Pustular Psoriasis (GPP) skin score scores for the total area of erythema with pustules (small pockets of pus) were calculated according to Japan Dermatology Association (JDA) severity index in GPP medical care guideline 2014. The total erythema area with pustules is evaluated on a scale of 0 (none) to 3 (severe), with the percentage of body surface area involvement defined as follows: severe ≥ 50%; moderate, ≥ 10% and < 50%; mild, < 10%); and none (0%). Negative values indicate improvement from baseline. | Baseline, Week 2, Week 4, Week 8, Week 12, Week 16, Week 24, Week 36, Week 52 | 
| Mean Change From Baseline in Total Edema Area Over Time | The Generalized Pustular Psoriasis (GPP) skin score scores for the total area of edema (swelling) were calculated according to Japan Dermatology Association (JDA) severity index in GPP medical care guideline 2014. The total area of edema is evaluated on a scale of 0 (none) to 3 (severe), with the percentage of body surface area involvement defined as follows: severe ≥ 50%; moderate, ≥ 10% and < 50%; mild, < 10%); and none (0%). Negative values indicate improvement from baseline. | Baseline, Week 2, Week 4, Week 8, Week 12, Week 16, Week 24, Week 36, Week 52 | 
| Mean Change From Baseline in Body Temperature Over Time | Body temperature (oral) was obtained at each visit prior to blood sampling. | Baseline, Week 2, Week 4, Week 8, Week 12, Week 16, Week 24, Week 36, Week 52 | 
| Mean Change From Baseline in White Blood Cell (WBC) Concentration Over Time | Blood was drawn at each study visit, and white blood cell concentration was determined. | Baseline, Week 2, Week 4, Week 8, Week 12, Week 16, Week 24, Week 36, Week 52 | 
| Mean Change From Baseline in High-Sensitivity C-Reactive Protein (Hs-CRP) Over Time | Blood was drawn at each study visit, and high-sensitivity C-reactive protein (hs-CRP) concentration was determined. | Baseline, Week 2, Week 4, Week 8, Week 12, Week 16, Week 24, Week 36, Week 52 | 
| Mean Change From Baseline in Serum Albumin Over Time | Blood was drawn at each study visit, and serum albumin concentration was determined. | Baseline, Week 2, Week 4, Week 8, Week 12, Week 16, Week 24, Week 36, Week 52 | 
| Number of Participants Achieving Mild in the JDA Severity Index of Generalized Pustular Psoriasis (GPP) for Participants With Moderate or Severe at Baseline Over Time | The Generalized Pustular Psoriasis (GPP) total score (range 0-17, with 17 representing severe disease) was calculated according to Japan Dermatology Association (JDA) severity index in GPP medical care guideline 2014. The total skin score (range 0-9, with 9 representing severe symptoms) is the combined skin scores for area of erythema (redness), area of erythema with pustules (small pockets of pus), and area of edema (swelling). The systemic and laboratory results score ([range 0-8, with 8 representing severe disease] assesses body temperature, white blood cell [WBC] count, high-sensitivity C-reactive protein [hs-CRP], and serum albumin). A total score on the JDA severity index of 0-6 is categorized as Mild, Moderate is 7-10, and Severe is 11-17. | Baseline, Week 2, Week 4, Week 8, Week 12, Week 16, Week 24, Week 36, Week 52 | 
| Proportion of Participants Achieving Treatment Success in Physician's Global Assessment of Generalized Pustular Psoriasis (PGA-GPP) Over Time | The Physician's Global Assessment of Generalized Pustular Psoriasis (PGA-GPP) is a 6-point scale used to measure the severity of skin disease at the time of the qualified investigator's evaluation of the participant. The degree of overall severity was evaluated using the following categories: erythema, pustulation, and edema, and graded as follows. Grade 0 = cleared, except for residual discoloration; Grade 1 = minimal; Grade 2 = mild; Grade 3 = moderate; Grade 4 = severe; and Grade 5 = very severe. The score is an arithmetic average of the grades for erythema, pustulation, and edema, rounded to the nearest whole number. Treatment Success was defined by at least a 2 grade improvement relative to baseline. | Baseline, Week 2, Week 4, Week 8, Week 12, Week 16, Week 24, Week 36, Week 52 | 
| Change From Baseline in Physician's Global Assessment of Generalized Pustular Psoriasis (PGA-GPP) Grade Over Time | The Physician's Global Assessment of Generalized Pustular Psoriasis (PGA-GPP) is a 6-point scale used to measure the severity of skin disease at the time of the qualified investigator's evaluation of the participant. The degree of overall severity was evaluated using the following categories: erythema, pustulation, and edema, and graded as follows. Grade 0 = cleared, except for residual discoloration; Grade 1 = minimal; Grade 2 = mild; Grade 3 = moderate; Grade 4 = severe; and Grade 5 = very severe. The score is an arithmetic average of the grades for erythema, pustulation, and edema, rounded to the nearest whole number. | Baseline, Week 2, Week 4, Week 8, Week 12, Week 16, Week 24, Week 36, Week 52 | 
| Proportion of Participants Achieving Physician's Global Assessment of Generalized Pustular Psoriasis (PGA-GPP) Grade 0 or 1 for Those With PGA Grade of at Least 2 at Baseline Over Time | The Physician's Global Assessment of Generalized Pustular Psoriasis (PGA-GPP) is a 6-point scale used to measure the severity of skin disease at the time of the qualified investigator's evaluation of the participant. The degree of overall severity was evaluated using the following categories: erythema, pustulation, and edema, and graded as follows. Grade 0 = cleared, except for residual discoloration; Grade 1 = minimal; Grade 2 = mild; Grade 3 = moderate; Grade 4 = severe; and Grade 5 = very severe. The score is an arithmetic average of the grades for erythema, pustulation, and edema, rounded to the nearest whole number. | Baseline, Week 2, Week 4, Week 8, Week 12, Week 16, Week 24, Week 36, Week 52 | 
| Proportion of Participants Achieving Psoriasis Area and Severity Index 90 (PASI 90) Over Time | The proportion of participants with a ≥ 90% reduction (improvement) in the Psoriasis Area and Severity Index (PASI) score from baseline was calculated. PASI is a combination of the intensity of psoriasis, assessed for erythema (reddening), induration (plaque thickness) and desquamation (scaling) on a scale from no symptoms (0), slight (1), moderate (2), marked (3) or very marked (4), together with the percentage of the area affected, rated on a scale from 0 to 6. PASI scoring is performed at four body areas, the head, arms, trunk, and legs. The total PASI score ranges from 0 to 72. The higher the total score, the more severe the disease. | Baseline, Week 2, Week 4, Week 8, Week 12, Week 16, Week 24, Week 36, Week 52 | 
| Proportion of Participants Achieving Psoriasis Area and Severity Index 75 (PASI 75) Over Time | The proportion of participants with a ≥ 75% reduction (improvement) in the Psoriasis Area and Severity Index (PASI) score from baseline was calculated. PASI is a combination of the intensity of psoriasis, assessed for erythema (reddening), induration (plaque thickness) and desquamation (scaling) on a scale from no symptoms (0), slight (1), moderate (2), marked (3) or very marked (4), together with the percentage of the area affected, rated on a scale from 0 to 6. PASI scoring is performed at four body areas, the head, arms, trunk, and legs. The total PASI score ranges from 0 to 72. The higher the total score, the more severe the disease. | Baseline, Week 2, Week 4, Week 8, Week 12, Week 16, Week 24, Week 36, Week 52 | 
| Proportion of Participants Achieving Psoriasis Area and Severity Index 50 (PASI 50) Over Time | The proportion of participants with a ≥ 50% reduction (improvement) in the Psoriasis Area and Severity Index (PASI) score from baseline was calculated. PASI is a combination of the intensity of psoriasis, assessed for erythema (reddening), induration (plaque thickness) and desquamation (scaling) on a scale from no symptoms (0), slight (1), moderate (2), marked (3) or very marked (4), together with the percentage of the area affected, rated on a scale from 0 to 6. PASI scoring is performed at four body areas, the head, arms, trunk, and legs. The total PASI score ranges from 0 to 72. The higher the total score, the more severe the disease. | Baseline, Week 2, Week 4, Week 8, Week 12, Week 16, Week 24, Week 36, Week 52 | 
| Mean Change From Baseline in Psoriasis Area and Severity Index (PASI) Score Over Time | The mean change in the Psoriasis Area and Severity Index (PASI) score from baseline was calculated. PASI is a combination of the intensity of psoriasis, assessed for erythema (reddening), induration (plaque thickness) and desquamation (scaling) on a scale from no symptoms (0), slight (1), moderate (2), marked (3) or very marked (4), together with the percentage of the area affected, rated on a scale from 0 to 6. PASI scoring is performed at four body areas, the head, arms, trunk, and legs. The total PASI score ranges from 0 to 72. The higher the total score, the more severe the disease. Negative values indicate improvement from baseline. | Baseline, Week 2, Week 4, Week 8, Week 12, Week 16, Week 24, Week 36, Week 52 | 
| Mean Percent Change From Baseline in Psoriasis Area and Severity Index (PASI) Score Over Time | The percent change in the Psoriasis Area and Severity Index (PASI) score from baseline was calculated. PASI is a combination of the intensity of psoriasis, assessed for erythema (reddening), induration (plaque thickness) and desquamation (scaling) on a scale from no symptoms (0), slight (1), moderate (2), marked (3) or very marked (4), together with the percentage of the area affected, rated on a scale from 0 to 6. PASI scoring is performed at four body areas, the head, arms, trunk, and legs. The total PASI score ranges from 0 to 72. The higher the total score, the more severe the disease. Negative values indicate improvement from baseline. | Baseline, Week 2, Week 4, Week 8, Week 12, Week 16, Week 24, Week 36, Week 52 | 
| Proportion of Participants Achieving Dermatology Life Quality Index (DLQI) Score of 0 Over Time | The DLQI questionnaire asks participants to evaluate the degree that psoriasis has affected their quality of life in the last week, and includes the following parameters: symptoms and feelings, daily activities, leisure activities, work or school activities, personal relationships and treatment- related feelings. Participants respond to 10 questions on a scale from 0 (not at all) to 3 (very much); the range of the total score is 0 to 30. A score of 21 to 30 means that psoriasis has an extremely large effect on the participant's life whereas 0-1 means that the disease has no effect at all. | Week 8, Week 16, Week 24, Week 36, Week 52 | 
| Mean Change From Baseline in Dermatology Life Quality Index (DLQI) Score Over Time | The DLQI questionnaire asks participants to evaluate the degree that psoriasis has affected their quality of life in the last week, and includes the following parameters: symptoms and feelings, daily activities, leisure activities, work or school activities, personal relationships and treatment- related feelings. Participants respond to 10 questions on a scale from 0 (not at all) to 3 (very much); the range of the total score is 0 to 30. A score of 21 to 30 means that psoriasis has an extremely large effect on the participant's life whereas 0-1 means that the disease has no effect at all. Negative values indicate improvement from baseline. | Baseline, Week 8, Week 16, Week 24, Week 36, Week 52 | 
| Mean Change From Baseline in Short Form-36 Health Status Survey Version 2 (SF-36 V2) Score Over Time | The Short Form-36 Health Status Survey Version 2 (SF-36 V2) is a 36-item generic health-related quality of life questionnaire to assess the participant's view of their health consisting of 2 components: physical and mental. For each component, a transformed summary score is calculated using 8 sub-domains: physical functioning, role-physical, bodily pain, general health, vitality, social functioning, role-emotional, and mental health. Scores range from 0 to 100. Higher scores indicate a better health state. | Baseline, Week 8, Week 16, Week 24, Week 36, Week 52 | 
| Proportion of Participants Taking Systemic Co-medication for Generalized Pustular Psoriasis (GPP) at Any Time During the Study | GPP-specific co-medications were documented at each scheduled study visit. | Baseline, Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24, Week 28, Week 32, Week 36, Week 40, Week 44, Week 48, Week 52 | 
| Proportion of Participants Taking Topical Co-medication for Generalized Pustular Psoriasis (GPP) at Any Time During the Study | Participants using topical co-medications for GPP were documented at each scheduled study visit. | Baseline, Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24, Week 28, Week 32, Week 36, Week 40, Week 44, Week 48, Week 52 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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efficacy, safety