Study of Secukinumab Compared to Fumaderm® in Adults With Moderate to Severe Psoriasis.

Study Overview
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Brief Summary
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This is a randomized, controlled, multicenter, open-label study with blinded assessment of the efficacy of subcutaneous secukinumab compared to Fumaderm®, in 200 adults with moderate to severe plaque type psoriasis who are candidates for systemic therapy. The study consists of 2 periods: a screening period of at least one week and up to four weeks, and a treatment period of 24 weeks. During the screening period eligibility of the patients is confirmed. Eligible patients are randomized 1:1 to treatment arm A or B at week 0. Patients in treatment arm A receive secukinumab administered at weeks 0, 1, 2, 3, 4, 8, 12, 16 and 20 and are followed up for assessments of the study endpoints until week 24. Patients in treatment arm B receive daily doses of Fumaderm® p.o.. Safety and efficacy measurements of secukinumab and Fumaderm® will be performed throughout the study and up to week 24.

Official Title
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A Randomized, Controlled, Multicenter, Open-label Study With Blinded Assessment of the Efficacy of Subcutaneous Secukinumab Compared to Fumaderm® in Adults With Moderate to Severe Plaque Psoriasis.

Conditions
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Psoriasis

Intervention / Treatment
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* Biological: Secukinumab
* Drug: Fumaric acid


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Men or women must be at least 18 years of age at the time of screening Chronic plaque-type psoriasis diagnosed for at least 6 months before randomization Patients with moderate to severe plaque psoriasis who are candidates for systemic therapy as defined at randomization by: PASI score of >10 Affected body surface area (BSA) > 10% DLQI >10 Inadequate response, intolerance or contraindication to topical psoriasis treatment as documented in the patient's medical history or reported by the patient or determined by the investigator at screening. Exclusion Criteria (abbreviated): Previous systemic treatment of plaque psoriasis or known contraindication for systemic therapy at baseline Ongoing use of other prohibited psoriasis and non-psoriasis treatment. Clinically important active infections or infestations, chronic, recurrent or latent infections or infestations Patients with severe liver diseases Patients with severe gastrointestinal diseases including but not limited to ventricular and duodenal ulcers Patients with severe kidney diseases or serum creatinine above 1 x ULN Patients with known hematological disease or lab abnormalities Pregnancy, breast feeding, or unwillingness/inability to use appropriate measures of contraception (if necessary)

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 |
| --- | --- |
| Experimental: Secukinumab<br>Patients in treatment arm A will receive a dose of 300 mg secukinumab administered as 2 subcutaneous injections of 150 mg in a SensoReady pen (i.e. 2 x 150 mg) at weeks 0, 1, 2, 3, 4, 8, 12, 16 and 20. | Biological: Secukinumab<br>* Secukinumab 150 mg, 1 ml liquid formulation in a pre-filled pen for s.c. injection<br>* Other names: AIN457;|
| Active Comparator: Fumaric acid (initial and maintenance therapy)<br>Participants were daily self-administered with fumaric acid derivatives initial and maintenance therapy in dosetitrated scheme as per protocol. Dose was up-titrated weekly (1 tablet/day) until objective was achieved or until tapering was required or until the maximum dose of 2 tablets each at morning, noon and evening was reached, whichever occurred earlier. | Drug: Fumaric acid<br>* Fumaric acid initial therapy (tablet contains 30 mg dimethylfumarate, 67 mg ethylhydrogenfumarate calcium salt, 5 mg ethylhydrogenfumarate magnesium salt, 3 mg ethylhydrogenfumarate zinc salt) and Fumaric acid maintenance therapy (tablet contains 120 mg dimethylfumarate, 87 mg ethylhydrogenfumarate calcium salt, 5 mg ethylhydrogenfumarate magnesium salt, 3 mg ethylhydrogenfumarate zinc salt)<br>* Other names: Fumarate, Fumaric acid, Fumaric acid esters;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Achieving Psoriasis Area and Severity Index (PASI) 75 Response at Week 24 | PASI score is an average degree of severity of signs in head [H], trunk [T], upper limbs [U] and lower limbs [L], assessed separately for erythema [E], thickening (plaque elevation, induration) [I], and scaling (desquamation) [D]. Area [A] covered by lesions on each body region was estimated as a percentage (%) of total area of that particular body region and was assigned a score of 0=0%; 1=1-9%; 2=10-29%; 3=30-49%; 4=50-69%; 5=70-89%; 6=90-100%. The head and neck, upper limbs, trunk and lower limbs correspond to approximately 10%, 20%, 30% and 40% of the body surface area, respectively. PASI score was calculated as: PASI = 0.1(EH+IH+DH) AH + 0.2(EU+IU+DU) AU + 0.3(ET+IT+DT) AT + 0.4(EL+IL+DL) AL. PASI scores can range from 0 (no signs) to a maximum of 72.0. PASI 75 responders were participants who achieved >=75% improvement (reduction) in PASI score compared to baseline. | Baseline, Week 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Achieving Psoriasis Area and Severity Index (PASI) 50 Response at Week 1, 2, 3, 4, 6, 8, 12, 16, 20 and 24 | PASI score is an average degree of severity of signs in head [H], trunk [T], upper limbs [U] and lower limbs [L], assessed separately for erythema [E], thickening (plaque elevation, induration) [I], and scaling (desquamation) [D]. Area [A] covered by lesions on each body region was estimated as a percentage (%) of total area of that particular body region and was assigned a score of 0=0%; 1=1-9%; 2=10-29%; 3=30-49%; 4=50-69%; 5=70-89%; 6=90-100%. The head and neck, upper limbs, trunk and lower limbs correspond to approximately 10%, 20%, 30% and 40% of the body surface area, respectively. PASI score was calculated as: PASI = 0.1(EH+IH+DH) AH + 0.2(EU+IU+DU) AU + 0.3(ET+IT+DT) AT + 0.4(EL+IL+DL) AL. PASI scores can range from 0 (no signs) to a maximum of 72.0. PASI 50 responders were participants who achieved >=50% improvement (reduction) in PASI score compared to baseline. | Baseline, Week 1, 2, 3, 4, 6, 8, 12, 16, 20 and 24 | 
| Percentage of Participants Achieving Psoriasis Area and Severity Index (PASI) 75 Response at Week 1, 2, 3, 4, 6, 8, 12, 16 and 20 | PASI score is an average degree of severity of signs in head [H], trunk [T], upper limbs [U] and lower limbs [L], assessed separately for erythema [E], thickening (plaque elevation, induration) [I], and scaling (desquamation) [D]. Area [A] covered by lesions on each body region was estimated as a percentage (%) of total area of that particular body region and was assigned a score of 0=0%; 1=1-9%; 2=10-29%; 3=30-49%; 4=50-69%; 5=70-89%; 6=90-100%. The head and neck, upper limbs, trunk and lower limbs correspond to approximately 10%, 20%, 30% and 40% of the body surface area, respectively. PASI score was calculated as: PASI = 0.1(EH+IH+DH) AH + 0.2(EU+IU+DU) AU + 0.3(ET+IT+DT) AT + 0.4(EL+IL+DL) AL. PASI scores can range from 0 (no signs) to a maximum of 72.0. PASI 75 responders were participants who achieved >=75% improvement (reduction) in PASI score compared to baseline. | Baseline, Week 1, 2, 3, 4, 6, 8, 12, 16 and 20 | 
| Percentage of Participants Achieving Psoriasis Area and Severity Index (PASI) 90 Response at Week 1, 2, 3, 4, 6, 8, 12, 16, 20 and 24 | PASI score is an average degree of severity of signs in head [H], trunk [T], upper limbs [U] and lower limbs [L], assessed separately for erythema [E], thickening (plaque elevation, induration) [I], and scaling (desquamation) [D]. Area [A] covered by lesions on each body region was estimated as a percentage (%) of total area of that particular body region and was assigned a score of 0=0%; 1=1-9%; 2=10-29%; 3=30-49%; 4=50-69%; 5=70-89%; 6=90-100%. The head and neck, upper limbs, trunk and lower limbs correspond to approximately 10%, 20%, 30% and 40% of the body surface area, respectively. PASI score was calculated as: PASI = 0.1(EH+IH+DH) AH + 0.2(EU+IU+DU) AU + 0.3(ET+IT+DT) AT + 0.4(EL+IL+DL) AL. PASI scores can range from 0 (no signs) to a maximum of 72.0. PASI 90 responders were participants who achieved >=90% improvement (reduction) in PASI score compared to baseline. | Baseline, Week 1, 2, 3, 4, 6, 8, 12, 16, 20 and 24 | 
| Percentage of Participants Achieving Psoriasis Area and Severity Index (PASI) 100 Response at Week 1, 2, 3, 4, 6, 8, 12, 16, 20 and 24 | PASI score is an average degree of severity of signs in head [H], trunk [T], upper limbs [U] and lower limbs [L], assessed separately for erythema [E], thickening (plaque elevation, induration) [I], and scaling (desquamation) [D]. Area [A] covered by lesions on each body region was estimated as a percentage (%) of total area of that particular body region and was assigned a score of 0=0%; 1=1-9%; 2=10-29%; 3=30-49%; 4=50-69%; 5=70-89%; 6=90-100%. The head and neck, upper limbs, trunk and lower limbs correspond to approximately 10%, 20%, 30% and 40% of the body surface area, respectively. PASI score was calculated as: PASI = 0.1(EH+IH+DH) AH + 0.2(EU+IU+DU) AU + 0.3(ET+IT+DT) AT + 0.4(EL+IL+DL) AL. PASI scores can range from 0 (no signs) to a maximum of 72.0. PASI 100 responders were participants who achieved complete clearance of psoriasis (PASI=0). | Baseline, Week 1, 2, 3, 4, 6, 8, 12, 16, 20 and 24 | 
| Body Surface Area (BSA) at Week 1, 2, 3, 4, 6, 8, 12, 16, 20 and 24 | The Body surface area (BSA) affected by plaque-type psoriasis was the total of percentages of areas affected, including head, trunk, upper limbs and lower limbs. Each reported percentage was multiplied by its respective body region corresponding factor (head = 0.1, trunk = 0.3, upper limbs = 0.2, lower limbs = 0.4). The resulting four percentages were added to estimate the total BSA affected by plaque-type psoriasis. | Week 1, 2, 3, 4, 6, 8, 12, 16, 20 and 24 | 
| Percentage of Participants Achieving Nail Psoriasis Severity Index (NAPSI) 50 Response at Week 1, 2, 3, 4, 6, 8, 12, 16, 20 and 24 | NAPSI was used to assess psoriatic nail involvement in participants with nail psoriasis. NAPSI score was calculated as total of nail matrix and nail bed score, ranging from 0-8 per nail. Total NAPSI score ranges from 0 to 80 for all fingernails. Each nail was divided with imaginary horizontal and longitudinal lines into quadrants. Each nail was given a score of 0 - 4 for nail matrix and nail bed psoriasis 0-4 (0: for none, 1: for 1 quadrant, 2: for 2 quadrants, 3: for 3 quadrants, 4: for all 4 quadrants), based on presence of any feature of nail psoriasis in that quadrant. Nail matrix psoriasis feature includes: pitting, leukonychia red spots in lunula, crumbling. Nail bed psoriasis feature includes: onycholysis, splinter hemorrhages, subungual hyperkeratosis, oil drop (salmon patch dyschroma). NPASI 50 responders were participants who achieved >=50% improvement (reduction) in NPASI score compared to baseline. | Baseline, Week 1, 2, 3, 4, 6, 8, 12, 16, 20 and 24 | 
| Percentage of Participants Achieving Nail Psoriasis Severity Index (NAPSI) 75 Response at Week 1, 2, 3, 4, 6, 8, 12, 16, 20 and 24 | NAPSI was used to assess psoriatic nail involvement in participants with nail psoriasis. NAPSI score was calculated as total of nail matrix and nail bed score, ranging from 0-8 per nail. Total NAPSI score ranges from 0 to 80 for all fingernails. Each nail was divided with imaginary horizontal and longitudinal lines into quadrants. Each nail was given a score of 0 - 4 for nail matrix and nail bed psoriasis 0-4 (0: for none, 1: for 1 quadrant, 2: for 2 quadrants, 3: for 3 quadrants, 4: for all 4 quadrants), based on presence of any feature of nail psoriasis in that quadrant. Nail matrix psoriasis feature includes: pitting, leukonychia red spots in lunula, crumbling. Nail bed psoriasis feature includes: onycholysis, splinter hemorrhages, subungual hyperkeratosis, oil drop (salmon patch dyschroma). NPASI 75 responders were participants who achieved >=75% improvement (reduction) in NPASI score compared to baseline. | Baseline, Week 1, 2, 3, 4, 6, 8, 12, 16, 20 and 24 | 
| Percentage of Participants Achieving Nail Psoriasis Severity Index (NAPSI) 90 Response at Week 1, 2, 3, 4, 6, 8, 12, 16, 20 and 24 | NAPSI was used to assess psoriatic nail involvement in participants with nail psoriasis. NAPSI score was calculated as total of nail matrix and nail bed score, ranging from 0-8 per nail. Total NAPSI score ranges from 0 to 80 for all fingernails. Each nail was divided with imaginary horizontal and longitudinal lines into quadrants. Each nail was given a score of 0 - 4 for nail matrix and nail bed psoriasis 0-4 (0: for none, 1: for 1 quadrant, 2: for 2 quadrants, 3: for 3 quadrants, 4: for all 4 quadrants), based on presence of any feature of nail psoriasis in that quadrant. Nail matrix psoriasis feature includes: pitting, leukonychia red spots in lunula, crumbling. Nail bed psoriasis feature includes: onycholysis, splinter hemorrhages, subungual hyperkeratosis, oil drop (salmon patch dyschroma). NPASI 90 responders were participants who achieved >=90% improvement (reduction) in NPASI score compared to baseline. | Baseline, Week 1, 2, 3, 4, 6, 8, 12, 16, 20 and 24 | 
| Percentage of Participants Achieving Nail Psoriasis Severity Index (NAPSI) 100 Response at Week 1, 2, 3, 4, 6, 8, 12, 16, 20 and 24 | NAPSI was used to assess psoriatic nail involvement in participants with nail psoriasis. NAPSI score was calculated as total of nail matrix and nail bed score, ranging from 0-8 per nail. Total NAPSI score ranges from 0 to 80 for all fingernails. Each nail was divided with imaginary horizontal and longitudinal lines into quadrants. Each nail was given a score of 0 - 4 for nail matrix and nail bed psoriasis 0-4 (0: for none, 1: for 1 quadrant, 2: for 2 quadrants, 3: for 3 quadrants, 4: for all 4 quadrants), based on presence of any feature of nail psoriasis in that quadrant. Nail matrix psoriasis feature includes: pitting, leukonychia red spots in lunula, crumbling. Nail bed psoriasis feature includes: onycholysis, splinter hemorrhages, subungual hyperkeratosis, oil drop (salmon patch dyschroma). NPASI 100 responders were participants who PASI 100 responders were participants who achieved complete clearance of psoriasis. | Baseline, Week 1, 2, 3, 4, 6, 8, 12, 16, 20 and 24 | 
| Number of Participants With Investigator's Global Assessment (IGA Mod 2011) at Week 1, 2, 3, 4, 6, 8, 12, 16, 20 and 24 | IGA mod 2011 is a global static severity rating scale referring exclusively to the participant's disease state at the time of the assessments and don't attempt comparison with participant's any previous disease states at baseline or visit. IGA mod 2011 has a scale of 0-4 with the lower scores correlating to better performance. Scores used were: 0/Clear: no signs of psoriasis, Post-inflammatory hyperpigmentation may be present; 1/almost clear: Normal to pink coloration of lesions/no thickening/no to minimal focal scaling; 2/Mild: Pink to light red coloration/just detectable to mild thickening/predominantly fine scaling; 3/Moderate: Dull bright red, clearly distinguishable erythema/clearly distinguishable to moderate thickening/moderate scaling; 4/Severe: Bright to deep dark red coloration/severe thickening with hard edges/severe or coarse scaling covering almost all or all lesions. | Week 1, 2, 3, 4, 6, 8, 12, 16, 20 and 24 | 
| Percentage of Participants With IGA Mod. 2011 0/1-response at Week 1, 2, 3, 4, 6, 8, 12, 16, 20 and 24 | The IGA mod 2011 scale has been developed based on a previous version of the scale used in secukinumab phase II studies in collaboration with health authorities, in particular the FDA. The explanations/descriptions of the points on the scale have been improved to ensure appropriate differentiation between the points. The IGA mod 2011 used in this study is static, i.e. it refers exclusively to the subject's disease state at the time of the assessments, and does not attempt a comparison with any of the subject's previous disease states, whether at baseline or at a previous visit.IGA mod 2011 has a scale of 0-4 with the lower scores correlating to better performance. A score of 0= clear skin, 1= almost clear skin, 2=mild, 3=moderate,4=severe. IGA 0/1 responders: who achieved score of 0/1 and improved by at least 2 points on the IGA scale compared to baseline. | Week 1, 2, 3, 4, 6, 8, 12, 16, 20 and 24 | 
| Dermatology Life Quality Index (DLQI) at Week 1, 2, 3, 4, 6, 8, 12, 16, 20 and 24 | DLQI is a 10-item general dermatology disability index designed to assess health-related quality of life in adult subjects with skin diseases such as eczema, psoriasis, acne, and viral. The measure was self-administered and included domains of daily activities, leisure, personal relationships, symptoms and feelings, treatment, and work/school. Each item had four response categories ranging from 0 (not at all) to 3 (very much). Not relevant was also a valid response and was scored as 0. The DLQI total score was a sum of the 10 questions. Scores ranged from 0 to 30, with higher scores indicating greater impairment in health related quality of life. | Week 1, 2, 3, 4, 6, 8, 12, 16, 20 and 24 | 
| Percentage of Participants With DLQI 0/1 Response at Week 1, 2, 3, 4, 6, 8, 12, 16, 20 and 24 | DLQI is a 10-item general dermatology disability index designed to assess health-related quality of life in adult subjects with skin diseases such as eczema, psoriasis, acne, and viral. The measure was self-administered and included domains of daily activities, leisure, personal relationships, symptoms and feelings, treatment, and work/school. Each item had four response categories ranging from 0 (not at all) to 3 (very much). Not relevant was also a valid response and was scored as 0. The DLQI total score was a sum of the 10 questions. Scores ranged from 0 to 30, with higher scores indicating greater impairment in health related quality of life. DLQI 0/1 response was the achievement of a DLQI score of 0 or 1. | Week 1, 2, 3, 4, 6, 8, 12, 16, 20 and 24 | 
| Percentage of Participants With Short Form 36 (SF-36) Response at Week 4, 16 and 24 | SF-36 is a generic indicator of health status for use in population surveys and evaluative studies of health policy. The SF-36 included 36 items in a Likert-type or forced-choice format measured on eight dimensions. The scores for each domain range from 0 to 100, with high scores indicating a better status. SF-36 responder is defined as subject reaching at least an improvement of minimum important difference (MID). The SF-36 measure dimensions and their MID includes: Physical Functioning:4.3 Role-Physical: 3.4 Bodily Pain: 6.2 General Health: 7.2 Vitality: 6.2 Social Functioning: 6.9 Role-Emotional: 4.5 Mental Health: 6.2 Two component scores and their MID which were derived from the above mentioned 8 domains includes-: Physical component summary: 3.4 Mental component summary: 4.6 | Week 4, 16 and 24 |