Palmoplantar Pustular Psoriasis Efficacy and Safety With Secukinumab

Study Overview
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Brief Summary
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A one year study assessing the efficacy and safety of secukinumab compared with placebo in adult patients with moderate to severe palmoplantar pustular psoriasis - amended with an optional extension treatment period of up to a total of 148 weeks

Official Title
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A 52-week, Multicenter, Randomized, Double-blind, Placebo-controlled Study of Subcutaneous Secukinumab to Demonstrate Efficacy as Assessed by Palmoplantar Pustulosis Psoriasis Area and Severity Index (ppPASI) at 16 Weeks of Treatment, Compared to Placebo, and to Assess Long-term Safety, Tolerability, and Efficacy in Subjects With Moderate to Severe Chronic Palmoplantar Pustular Psoriasis - Amended With an Optional Extension Treatment Period of up to a Total of 148 Weeks

Conditions
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Palmoplantar Pustular Psoriasis

Intervention / Treatment
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* Biological: Secukinumab 300mg
* Biological: Secukinumab 150mg
* Biological: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Palmoplantar pustular psoriasis for at least 6 months before Randomization Moderate to severe palmoplantar pustular psoriasis as defined at Baseline by: ppPASI score of ≥ 12 and DLQI ≥ 10 Candidate for systemic therapy, defined as having palmoplantar pustular psoriasis inadequately controlled by: Topical treatment, and/or Phototherapy, and/or Previous systemic therapy Exclusion Criteria: Forms of psoriasis other than chronic plaque psoriasis and pustular palmoplantar psoriasis (e.g., erythrodermic, guttate, or generalized pustular psoriasis) Drug-induced psoriasis (e.g., new onset or current exacerbation from beta-blockers, calcium channel inhibitors, or lithium) or history of proven contact dermatitis Patients not willing to limit UV light exposure (e.g. sunbathing and/or the use of tanning devices) during the course of the study Ongoing use of prohibited psoriasis treatments (e.g., topical or systemic corticosteroids, UV therapy). Washout periods detailed in the protocol have to be adhered to Previous exposure to any biologic drug directly targeting IL-17 or IL-17 Receptor (e.g., secukinumab, ixekizumab, or brodalumab) Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using effective methods of contraception during dosing of study treatment and for 16 weeks after stopping treatment Active ongoing inflammatory diseases other than psoriasis that might confound the evaluation of the benefit of secukinumab therapy Use of any other investigational drugs within 4 weeks of study drug initiation or within a period of 5 half-lives of the investigational treatment, whichever is longer Other protocol-defined inclusion/exclusion criteria may apply.

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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Secukinumab 300mg<br>Secukinumab 300mg once weekly at Weeks 1, 2 and 3, thereafter at 4-weekly intervals starting Week 4 until Week 48. In order to maintain the blinding beyond the primary endpoint, placebo was administered at Weeks 17, 18 and 19. For extension period: Secukinumab 300mg at 4-weekly intervals starting Week 52 up to Week 148. | Biological: Secukinumab 300mg<br>* Secukinumab was used as 150 mg pre-filled syringes (PFS) in a double-blinded fashion. Secukinumab 300 mg s.c. (two PFS injections of the 150 mg dose) self-administered<br>Biological: Placebo<br>* secukinumab placebo s.c. (two PFS injections of placebo) self-administered<br>|
| Experimental: Secukinumab 150mg<br>Secukinumab 150mg once weekly at Weeks 1, 2 and 3, thereafter at 4-weekly intervals starting Week 4 until Week 48. In order to maintain the blinding beyond the primary endpoint, placebo was administered at Weeks 17, 18 and 19. For extension period: Secukinumab 150mg at 4-weekly intervals starting Week 52 up to Week 148. | Biological: Secukinumab 150mg<br>* secukinumab 150 mg s.c. (one PFS injection of the 150 mg dose + one PFS injection of placebo) self-administered<br>Biological: Placebo<br>* secukinumab placebo s.c. (two PFS injections of placebo) self-administered<br>|
| Placebo Comparator: Placebo<br>Placebo once weekly at Weeks 1, 2 and 3, thereafter at 4-weekly intervals starting Week 4 until Week 12. Patients who achieved ppPASI 75 at Week 16 remained on placebo treatment Until week 48 and were not eligible to enter the extension. Patients who did not achieve ppPASI 75 at Week 16 were re-randomized to receive Secukinumab 150mg or Secukinumab 300mg from Week 16 onwards up to Week 148. | Biological: Secukinumab 300mg<br>* Secukinumab was used as 150 mg pre-filled syringes (PFS) in a double-blinded fashion. Secukinumab 300 mg s.c. (two PFS injections of the 150 mg dose) self-administered<br>Biological: Secukinumab 150mg<br>* secukinumab 150 mg s.c. (one PFS injection of the 150 mg dose + one PFS injection of placebo) self-administered<br>Biological: Placebo<br>* secukinumab placebo s.c. (two PFS injections of placebo) self-administered<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With ppPASI 75 Response at Week 16 (Period 1) | The primary endpoint was assessed by the palmoplantar pustulosis Psoriasis Area and Severity Index 75 (ppPASI 75). The percentage of subjects who achieved a 75% reduction in ppPASI score from Baseline to Week 16 was measured. The ppPASI is a modification of the PASI score and adjusted for palmoplantar pustular psoriasis by classifying and scoring erythema, scaling (desquamation) and pustules/vesicles. Both palms and both plants are scored from 0 to 4. The extent of involvement of each region of the body is scored from 0 to 6. The total ppPASI score can range from a lower level of 0, corresponding to no signs of psoriasis, up to a maximum of 72. | Baseline to Week 16 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ppPASI: Absolute Change From Baseline to Week 16 | A secondary endpoint was assessed by the palmoplantar pustulosis Psoriasis Area and Severity Index (ppPASI). The mean change of ppPASI score from Baseline to Week 16 was measured. The ppPASI is a modification of the PASI score and adjusted for palmoplantar pustular psoriasis by classifying and scoring erythema, scaling (desquamation) and pustules/vesicles. Both palms and both plants are scored from 0 to 4. The extent of involvement of each region is scored from 0 to 6. The total ppPASI score can range from a lower level of 0, corresponding to no signs of psoriasis, up to a maximum of 72. | Baseline to Week 16 | 
| Percentage of Participants With ppPASI 75 Response Over Time (Period 1) | A secondary endpoint was assessed as response rate of patients to treatment measured by the palmoplantar pustulosis Psoriasis Area and Severity Index 75 (ppPASI 75). The percentage of subjects who achieve a 75% reduction in ppPASI score from Baseline to each post-baseline visit is measured. The ppPASI is a modification of the PASI score and adjusted for palmoplantar pustular psoriasis by classifying and scoring erythema, scaling (desquamation) and pustules/vesicles. Both palms and both plants are scored from 0 to 4. The extent of involvement of each region of the body is scored from 0 to 6. The total ppPASI score can range from a lower level of 0, corresponding to no signs of psoriasis, up to a maximum of 72. | Baseline to Week 16 | 
| Percentage of Participants With ppPASI 75 Response Over Time (Period 2) | A secondary endpoint was assessed as response rate of patients to treatment measured by the palmoplantar pustulosis Psoriasis Area and Severity Index 75 (ppPASI 75). The percentage of subjects who achieve a 75% reduction in ppPASI score from Baseline to each post-baseline visit is measured. The ppPASI is a modification of the PASI score and adjusted for palmoplantar pustular psoriasis by classifying and scoring erythema, scaling (desquamation) and pustules/vesicles. Both palms and both plants are scored from 0 to 4. The extent of involvement of each region of the body is scored from 0 to 6. The total ppPASI score can range from a lower level of 0, corresponding to no signs of psoriasis, up to a maximum of 72. | Week 16 to Week 52 | 
| Percentage of Participants With ppPASI 75 Response Over Time (Extension Period) | A secondary endpoint was assessed as response rate of patients to treatment measured by the palmoplantar pustulosis Psoriasis Area and Severity Index 75 (ppPASI 75). The percentage of subjects who achieved a 75% reduction in ppPASI score from Baseline to each post-baseline visit was measured. The ppPASI is a modification of the PASI score and adjusted for palmoplantar pustular psoriasis by classifying and scoring erythema, scaling (desquamation) and pustules/vesicles. Both palms and both plants are scored from 0 to 4. The extent of involvement of each region of the body is scored from 0 to 6. The total ppPASI score can range from a lower level of 0, corresponding to no signs of psoriasis, up to a maximum of 72. | Week 52 to Week 148 | 
| Percentage of Participants With Most Frequent Adverse Events - Period 1 (Patient's Safety) | Most frequent (at least 5% in any of the AIN457 groups) Adverse Events | Baseline to Week 16 (Period 1) | 
| Percentage of Participants With Most Frequent Adverse Events - Period 2 (Patient's Safety) | Most frequent (at least 5% in any of the AIN457 groups) Adverse Events | Week 16 to Week 52 (Period 2) | 
| Percentage of Participants With Most Frequent Adverse Events - Extension Period (Patient's Safety) | Most frequent (at least 5% in any of the AIN457 groups) Adverse Events | Week 52 to Week 148 (extension period) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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palmoplantar, pustular, psoriasis