Clinical Trial Results:
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.
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Summary
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EudraCT number |
2014-005258-20 |
Trial protocol |
DE |
Global end of trial date |
13 Jun 2016
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Results information
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Results version number |
v1(current) |
This version publication date |
27 Jun 2017
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First version publication date |
27 Jun 2017
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Other versions |
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Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
CAIN457ADE06
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT02474082 | ||
WHO universal trial number (UTN) |
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Sponsors
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Sponsor organisation name |
Novartis Pharma AG
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Sponsor organisation address |
CH-4002, Basel, Switzerland,
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Public contact |
Clinical Disclosure Office, Novartis Pharma AG, +41 613241111,
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Scientific contact |
Clinical Disclosure Office, Novartis Pharma AG, +41 613241111,
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
13 Jun 2016
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Is this the analysis of the primary completion data? |
No
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Global end of trial reached? |
Yes
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Global end of trial date |
13 Jun 2016
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
The primary study objective was to demonstrate the superiority of secukinumab compared to Fumaric Acid in subjects with moderate to severe plaque psoriasis based on the proportion of Psoriasis Area Severity Index (PASI) 75 responders at week 24.
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Protection of trial subjects |
The study was in compliance with the ethical principles derived from the Declaration of Helsinki and the International Conference on Harmonization (ICH) Good Clinical Practice (GCP) guidelines. All the local regulatory requirements pertinent to safety of trial subjects were also followed during the conduct of the trial.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
15 Apr 2015
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Germany: 202
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Worldwide total number of subjects |
202
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EEA total number of subjects |
202
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
188
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From 65 to 84 years |
14
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85 years and over |
0
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Recruitment
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Recruitment details |
- | |||||||||||||||||||||||||||||||||||||||
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Pre-assignment
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Screening details |
A total of 202 (secukinumab: 105 and fumaric acid derivatives: 97) subjects were randomized in the study out of which 200 (secukinumab: 105 and fumaric acid derivatives: 95) received treatment. 2 subjects were discontinued from the study due to non-compliance with study treatment (1) and withdrawal of informed consent (1). | |||||||||||||||||||||||||||||||||||||||
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Period 1
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Period 1 title |
Overall Study (overall period)
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Is this the baseline period? |
Yes | |||||||||||||||||||||||||||||||||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Single blind | |||||||||||||||||||||||||||||||||||||||
Roles blinded |
Assessor [1] | |||||||||||||||||||||||||||||||||||||||
Blinding implementation details |
This was an open label study. However, a blinded assessor performed all non-subject-reported efficacy assessments to minimize bias.
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Secukinumab | |||||||||||||||||||||||||||||||||||||||
Arm description |
Subjects were self-administered subcutaneously (s.c.) with a dose of 300 milligrams (mg) of secukinumab at weeks 0, 1, 2, 3, 4, 8, 12, 16 and 20. Secukinumab was injected in non-affected areas of the skin at front of thighs or lower abdomen (but not the area 5 centimeters (cm) around the navel). | |||||||||||||||||||||||||||||||||||||||
Arm type |
Experimental | |||||||||||||||||||||||||||||||||||||||
Investigational medicinal product name |
Secukinumab
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Investigational medicinal product code |
AIN457
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Other name |
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Pharmaceutical forms |
Concentrate for solution for injection
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Routes of administration |
Subcutaneous use
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Dosage and administration details |
Secukinumab 150 mg [1 ml liquid formulation in a pre-filled pen for s.c. injection]
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Arm title
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Fumaric acid (initial and maintenance therapy) | |||||||||||||||||||||||||||||||||||||||
Arm description |
Subjects were daily self-administered with fumaric acid derivatives initial and maintenance therapy in dose-titrated 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. | |||||||||||||||||||||||||||||||||||||||
Arm type |
Active comparator | |||||||||||||||||||||||||||||||||||||||
Investigational medicinal product name |
Fumaric acid,
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
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)
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| Notes [1] - The roles blinded appear inconsistent with a simple blinded trial. Justification: A blinded assessor performed all non-subject-reported efficacy assessments to minimize bias. |
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Baseline characteristics reporting groups
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Reporting group title |
Secukinumab
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Reporting group description |
Subjects were self-administered subcutaneously (s.c.) with a dose of 300 milligrams (mg) of secukinumab at weeks 0, 1, 2, 3, 4, 8, 12, 16 and 20. Secukinumab was injected in non-affected areas of the skin at front of thighs or lower abdomen (but not the area 5 centimeters (cm) around the navel). | ||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Fumaric acid (initial and maintenance therapy)
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Reporting group description |
Subjects were daily self-administered with fumaric acid derivatives initial and maintenance therapy in dose-titrated 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. | ||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Secukinumab
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Reporting group description |
Subjects were self-administered subcutaneously (s.c.) with a dose of 300 milligrams (mg) of secukinumab at weeks 0, 1, 2, 3, 4, 8, 12, 16 and 20. Secukinumab was injected in non-affected areas of the skin at front of thighs or lower abdomen (but not the area 5 centimeters (cm) around the navel). | ||
Reporting group title |
Fumaric acid (initial and maintenance therapy)
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Reporting group description |
Subjects were daily self-administered with fumaric acid derivatives initial and maintenance therapy in dose-titrated 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. | ||
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End point title |
Percentage of subjects achieving Psoriasis Area and Severity Index (PASI) 75 Response at week 24 | ||||||||||||
End point description |
PASI score is 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 percentage (%) of total area of that particular body region and was assigned score of 0=0%; 1=1-9%; 2=10-29%; 3=30-49%; 4=50-69%; 5=70-89%; 6=90-100%. 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 maximum of 72. PASI 75 responders were subjects who achieved >=75% improvement (reduction) in PASI score compared to baseline. The analysis was performed in Full analysis set (FAS) population defined as all randomized subjects who received at least one dose of study drug.
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End point type |
Primary
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End point timeframe |
Baseline, Week 24
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Statistical analysis title |
PASI 75 response at week 24 | ||||||||||||
Comparison groups |
Secukinumab v Fumaric acid (initial and maintenance therapy)
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Number of subjects included in analysis |
200
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Analysis specification |
Pre-specified
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Analysis type |
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P-value |
< 0.0001 | ||||||||||||
Method |
Regression, Logistic | ||||||||||||
Parameter type |
Odds ratio (OR) | ||||||||||||
Point estimate |
16.61
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Confidence interval |
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level |
95% | ||||||||||||
sides |
2-sided
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lower limit |
7.79 | ||||||||||||
upper limit |
35.4 | ||||||||||||
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End point title |
Percentage of subjects achieving Psoriasis Area and Severity Index (PASI) 50 Response at week 1, 2, 3, 4, 6, 8, 12, 16, 20 and 24 | ||||||||||||||||||||||||||||||||||||||||||
End point description |
PASI score is 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 percentage(%) of total area of that particular body region and was assigned score of 0=0%; 1=1-9%; 2=10-29%; 3=30-49%; 4=50-69%; 5=70-89%; 6=90-100%. 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. PASI 50 responders were subjects who achieved >=50% improvement (reduction) in PASI score compared to baseline. The analysis was performed in FAS population. Here 'n' signifies subjects evaluable for PASI 50 at week 1, 2, 3, 4, 6, 8, 12, 16, 20 and 24.
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End point type |
Secondary
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End point timeframe |
Baseline, Week 1, 2, 3, 4, 6, 8, 12, 16, 20 and 24
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| No statistical analyses for this end point | |||||||||||||||||||||||||||||||||||||||||||
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End point title |
Percentage of subjects achieving Psoriasis Area and Severity Index (PASI) 75 Response at week 1, 2, 3, 4, 6, 8, 12, 16 and 20 | |||||||||||||||||||||||||||||||||||||||
End point description |
PASI score is 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 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%. 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. PASI 75 responders were subjects who achieved >=75% improvement (reduction) in PASI score compared to baseline. The analysis was performed in FAS population. Here 'n' signifies participants evaluable for PASI 75 at week 1, 2, 3, 4, 6, 8, 12, 16 and 20.
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End point type |
Secondary
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End point timeframe |
Baseline, Week 1, 2, 3, 4, 6, 8, 12, 16 and 20
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| No statistical analyses for this end point | ||||||||||||||||||||||||||||||||||||||||
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End point title |
Percentage of subjects achieving Psoriasis Area and Severity Index (PASI) 90 Response at week 1, 2, 3, 4, 6, 8, 12, 16, 20 and 24 | ||||||||||||||||||||||||||||||||||||||||||
End point description |
PASI score is 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 percentage(%) of total area of that particular body region and was assigned a score of 0=0%; 1=19%; 2=10-29%; 3=30-49%; 4=50-69%; 5=70-89%; 6=90-100%. 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 maximum of 72. PASI 90 responders were subjects who achieved >=90% improvement (reduction) in PASI score compared to baseline. The analysis was performed in FAS population. Here 'n' signifies subjects evaluable for PASI 90 at week 1, 2, 3, 4, 6, 8, 12, 16, 20 and 24.
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End point type |
Secondary
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End point timeframe |
Baseline, Week 1, 2, 3, 4, 6, 8, 12, 16, 20 and 24
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| No statistical analyses for this end point | |||||||||||||||||||||||||||||||||||||||||||
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End point title |
Percentage of subjects achieving Psoriasis Area and Severity Index (PASI) 100 Response at week 1, 2, 3, 4, 6, 8, 12, 16, 20 and 24 | ||||||||||||||||||||||||||||||||||||||||||
End point description |
PASI score is 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 maximum of 72. PASI 100 responders were subjects who achieved complete clearance of psoriasis (PASI=0). The analysis was performed in FAS population. Here 'n' signifies subjects evaluable for PASI 100 at week 1, 2, 3, 4, 6, 8, 12, 16, 20 and 24
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End point type |
Secondary
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End point timeframe |
Baseline, Week 1, 2, 3, 4, 6, 8, 12, 16, 20 and 24
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| No statistical analyses for this end point | |||||||||||||||||||||||||||||||||||||||||||
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End point title |
Body surface area (BSA) at week 1, 2, 3, 4, 6, 8, 12, 16, 20 and 24 | ||||||||||||||||||||||||||||||||||||||||||
End point description |
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. The analysis was performed in FAS population. Here 'n' signifies subjects evaluable for BSA at week 1, 2, 3, 4, 6, 8, 12, 16, 20 and 24.
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End point type |
Secondary
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End point timeframe |
Week 1, 2, 3, 4, 6, 8, 12, 16, 20 and 24
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| No statistical analyses for this end point | |||||||||||||||||||||||||||||||||||||||||||
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End point title |
Percentage of subjects achieving Nail Psoriasis Severity Index (NAPSI) 50 response at week 1, 2, 3, 4, 6, 8, 12, 16, 20 and 24 | ||||||||||||||||||||||||||||||||||||||||||
End point description |
NAPSI was used to assess psoriatic nail involvement in subjects with nail psoriasis. NAPSI = total of nail matrix and nail bed score, ranging from 0-8 per nail. Total NAPSI score ranges from 0-80 for all fingernails. Each nail was divided with imaginary horizontal and longitudinal lines into quadrants and given score 0-4 for nail matrix and nail bed psoriasis 0–4 (0: none, 1: 1 quadrant, 2: 2 quadrants, 3: 3 quadrants, 4: 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 subjects who achieved >=50% improvement (reduction) in NPASI score compared to baseline. The analysis was performed on FAS population. Here ‘n’ signifies subjects evaluable for NAPSI 50 at specified time point.
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End point type |
Secondary
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End point timeframe |
Baseline, Week 1, 2, 3, 4, 6, 8, 12, 16, 20 and 24
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| No statistical analyses for this end point | |||||||||||||||||||||||||||||||||||||||||||
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End point title |
Percentage of subjects achieving Nail Psoriasis Severity Index (NAPSI) 75 response at week 1, 2, 3, 4, 6, 8, 12, 16, 20 and 24 | ||||||||||||||||||||||||||||||||||||||||||
End point description |
NAPSI was used to assess psoriatic nail involvement in subjects with nail psoriasis. NAPSI=total of nail matrix and nail bed score, ranging from 0-8 per nail. Total NAPSI score ranges from 0-80 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: none, 1: 1 quadrant, 2: 2 quadrants, 3: 3 quadrants, 4: 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 subjects who achieved >=75% improvement (reduction) in NPASI score compared to baseline. The analysis was performed on FAS population. Here 'n' signifies subjects evaluable for NAPSI 75 at specified time point.
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End point type |
Secondary
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End point timeframe |
Baseline, Week 1, 2, 3, 4, 6, 8, 12, 16, 20 and 24
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| No statistical analyses for this end point | |||||||||||||||||||||||||||||||||||||||||||
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End point title |
Percentage of subjects achieving Nail Psoriasis Severity Index (NAPSI) 90 response at week 1, 2, 3, 4, 6, 8, 12, 16, 20 and 24 | ||||||||||||||||||||||||||||||||||||||||||
End point description |
NAPSI was used to assess psoriatic nail involvement in subjects with nail psoriasis. NAPSI = total of nail matrix and nail bed score, ranging from 0-8 per nail. Total NAPSI score ranges from 0-80 for all fingernails. Each nail was divided with imaginary horizontal and longitudinal lines into quadrants and given a score of 0-4 nail matrix and nail bed psoriasis 0–4 (0: none, 1: 1 quadrant, 2: 2 quadrants, 3: 3 quadrants, 4: 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 subjects who achieved >=90% improvement (reduction) in NPASI score compared to baseline. The analysis was performed on FAS population. Here 'n' signifies the subjects evaluable for NAPSI 90 response at specified time point.
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End point type |
Secondary
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End point timeframe |
Baseline, Week 1, 2, 3, 4, 6, 8, 12, 16, 20 and 24
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| No statistical analyses for this end point | |||||||||||||||||||||||||||||||||||||||||||
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End point title |
Percentage of subjects achieving Nail Psoriasis Severity Index (NAPSI) 100 response at week 1, 2, 3, 4, 6, 8, 12, 16, 20 and 24 | ||||||||||||||||||||||||||||||||||||||||||
End point description |
NAPSI was used to assess psoriatic nail involvement in subjects with nail psoriasis. NAPSI = total of nail matrix and nail bed score,ranging from 0-8 per nail. Total NAPSI score ranges from 0-80 for all fingernails. Each nail was divided with imaginary horizontal and longitudinal lines into quadrants and given score of 0-4 for nail matrix and nail bed psoriasis 0–4 (0: none, 1: 1 quadrant, 2: 2 quadrants, 3: 3 quadrants, 4: 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 subjects who PASI 100 responders were subjects who achieved complete clearance of psoriasis. Analysis was performed on FAS population. Here 'n' signifies the subjects evaluable for NAPSI 100 response at specified time point.
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End point type |
Secondary
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End point timeframe |
Baseline, Week 1, 2, 3, 4, 6, 8, 12, 16, 20 and 24
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| No statistical analyses for this end point | |||||||||||||||||||||||||||||||||||||||||||
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End point title |
Number of subjects with Investigator’s global assessment (IGA mod 2011) at week 1, 2, 3, 4, 6, 8, 12, 16, 20 and 24 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
IGA mod 2011 is a global static severity rating scale referring exclusively to the subject’s disease state at the time of the assessments and don’t attempt comparison with subject’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. The analysis was performed in FAS population. Here 'n' signifies the subjects evaluable for IGA mod 2011 at week
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End point type |
Secondary
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End point timeframe |
Week 1, 2, 3, 4, 6, 8, 12, 16, 20 and 24
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| No statistical analyses for this end point | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End point title |
Percentage of subjects with IGA mod. 2011 0/1-response at week 1, 2, 3, 4, 6, 8, 12, 16, 20 and 24 | ||||||||||||||||||||||||||||||||||||||||||
End point description |
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. The analysis was performed on FAS population. IGA 0/1 responders: who achieved score of 0/1 and improved by at least 2 points on the IGA scale compared to baseline.
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End point type |
Secondary
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End point timeframe |
Week 1, 2, 3, 4, 6, 8, 12, 16, 20 and 24
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| No statistical analyses for this end point | |||||||||||||||||||||||||||||||||||||||||||
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End point title |
Dermatology Life Quality Index (DLQI) at week 1, 2, 3, 4, 6, 8, 12, 16, 20 and 24 | ||||||||||||||||||||||||||||||||||||||||||
End point description |
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. The analysis was performed on FAS population. Here 'n' signifies the subjects evaluable for DLQI at week 1, 2, 3, 4, 6, 8, 12, 16, 20 and 24.
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End point type |
Secondary
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End point timeframe |
Week 1, 2, 3, 4, 6, 8, 12, 16, 20 and 24
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| No statistical analyses for this end point | |||||||||||||||||||||||||||||||||||||||||||
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End point title |
Percentage of subjects with DLQI 0/1 response at week 1, 2, 3, 4, 6, 8, 12, 16, 20 and 24 | ||||||||||||||||||||||||||||||||||||||||||
End point description |
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. The analysis was performed on FAS population.
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End point type |
Secondary
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End point timeframe |
Week 1, 2, 3, 4, 6, 8, 12, 16, 20 and 24
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| No statistical analyses for this end point | |||||||||||||||||||||||||||||||||||||||||||
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End point title |
Percentage of subjects with Short Form 36 (SF-36) response at week 4, 16 and 24 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
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.
The analysis was performed on FAS population. Here 'n' signifies the subjects evaluable for SF-36 response at week 4, 16 and 24.
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End point type |
Secondary
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End point timeframe |
Week 4, 16 and 24
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| No statistical analyses for this end point | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Adverse events information
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Timeframe for reporting adverse events |
Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit (up to 29 weeks).
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Adverse event reporting additional description |
The safety analysis set consisted of all patients who took at least one dose of study treatment during the treatment period.
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Assessment type |
Systematic | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
19.0
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Reporting groups
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Reporting group title |
Fumaric acid (initial and maintenance therapy)
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Reporting group description |
Participants were daily self-administered with fumaric acid derivatives initial and maintenance therapy in dose-titrated 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. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Secukinumab
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Reporting group description |
Participants were self-administered subcutaneously (s.c.) with a dose of 300 milligrams (mg) of secukinumab at weeks 0, 1, 2, 3, 4, 8, 12, 16 and 20. Secukinumab was injected in non-affected areas of the skin at front of thighs or lower abdomen (but not the area 5 centimeters (cm) around the navel). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 5% | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
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05 May 2015 |
This amendment came into effect when randomization was 6% completed in order to align study treatment with the German guidelines, to clarify handling of laboratory abnormalities and discontinuation criteria, and to introduce photography as an optional procedure in the study. Following changes were introduced:
• It was clarified that subject with hematology lab results >1 x upper limit to normal (ULN) or <1 x lower limit to normal can be included, if the laboratory abnormality is deemed clinically irrelevant by the investigator
• Based on a recommendation in the German guidelines, affected renal function (including but not limited to subject who experience proteinuria), was added a reason for dose tapering.
• It was clarified that pathological changes of blood counts are marked positive on the laboratory results of the central laboratory and that the decision, whether a change is deemed pathological and thus constitutes a reason for discontinuation, is at the discretion of the investigator.
• Based on a recommendation in the German guidelines, it was clarified that eosinophilia during fumaric acid treatment is usually transient and occurs between weeks 4 and 10 of treatment. Subject with eosinophilia, even if marked positive by the central laboratory, may continue the study, if eosinophilia is deemed transient and the overall benefit of continuing outweighs the risk at the discretion of the investigator.
• Signs and symptoms of progressive multifocal leukoencephalopathy (PML) were added as examples of AEs that, in the judgment of the investigator/qualified site staff, taking into account the patient’s overall status, might prevent the patient from continuing study treatment.
• Dispensing fumaric acid was added to the visit schedule. |
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08 Oct 2015 |
Amendment No. 2 introduced the following changes:
• For interaction with health technology assessment (HTA) bodies and payers, as interim analysis of the data available during the first quarter of 2016, or as required was introduced. The results were to be analyzed by an independent statistician and released to a pre-defined and limited group of Novartis personnel only for interactions with HTA bodies and payers. The clinical study team, the investigators, site personnel, and the subjects remained blinded to the result of the interim analysis until the full study data base was locked and the blinded data review meeting was completed.
• It was clarified that subjects with serum creatinine above 1 x ULN may be included, if the laboratory abnormality was deemed clinically irrelevant by the investigator.
• It was clarified that subjects treated with fumaric acid, who develop a serum creatinine above 1 x ULN, may continue in the study, if the laboratory abnormality was deemed clinically irrelevant by the investigator.
• A new inclusion criterion was added: “Subjects for whom fumaric acid is expected to be the patient individually optimized standard therapy under consideration of fumaric acid, ciclosporin, methotrexate or phototherapy as per investigator’s discretion.”
• The confirmation that fumaric acid was expected to be the patient-individually optimized standard therapy as per investigator’s discretion was to be documented as part of the baseline characteristics. If needed, the confirmation was allowed to be collected retrospectively.
• Discontinuation criteria were updated to reflect precautions with respect to PML.
• Examinations for signs and symptoms of PML were added to the visit schedule and assessments.
• Errors in the assessment schedule and assessments were corrected. |
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Interruptions (globally) |
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| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| None reported | |||
