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

Psoriasis Clinical Trial

— PRIME  

Official title:

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.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02474082
• Other study ID #: CAIN457ADE06
• Status: Completed
• Phase: Phase 3
• First received: April 16, 2015
• Last updated: June 11, 2017
• Start date: April 2015
• Est. completion date: June 2016

Study information

• Verified date: June 2017
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 202
• Est. completion date: June 2016
• Est. primary completion date: June 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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)

Related Conditions & MeSH terms

• Psoriasis

Intervention

Biological:
• Secukinumab
Secukinumab 150 mg, 1 ml liquid formulation in a pre-filled pen for s.c. injection

Drug:
• Fumaric acid
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)

Locations

Country	Name	City	State
Germany	Novartis Investigative Site	Bad Bentheim
Germany	Novartis Investigative Site	Berlin
Germany	Novartis Investigative Site	Berlin
Germany	Novartis Investigative Site	Berlin
Germany	Novartis Investigative Site	Berlin
Germany	Novartis Investigative Site	Berlin
Germany	Novartis Investigative Site	Bielefeld
Germany	Novartis Investigative Site	Bochum
Germany	Novartis Investigative Site	Bochum
Germany	Novartis Investigative Site	Bonn
Germany	Novartis Investigative Site	Darmstadt
Germany	Novartis Investigative Site	Erlangen
Germany	Novartis Investigative Site	Essen
Germany	Novartis Investigative Site	Frankfurt
Germany	Novartis Investigative Site	Gera
Germany	Novartis Investigative Site	Halle
Germany	Novartis Investigative Site	Hamburg
Germany	Novartis Investigative Site	Hamburg
Germany	Novartis Investigative Site	Hamburg
Germany	Novartis Investigative Site	Hannover
Germany	Novartis Investigative Site	Heidelberg
Germany	Novartis Investigative Site	Kiel
Germany	Novartis Investigative Site	Lubeck
Germany	Novartis Investigative Site	Ludwigshafen
Germany	Novartis Investigative Site	Mannheim
Germany	Novartis Investigative Site	Muenchen
Germany	Novartis Investigative Site	Muenster
Germany	Novartis Investigative Site	Osnabruck
Germany	Novartis Investigative Site	Quedlinburg
Germany	Novartis Investigative Site	Schwerin
Germany	Novartis Investigative Site	Selters
Germany	Novartis Investigative Site	Stade

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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