Palmoplantar Pustular Psoriasis Efficacy and Safety With Secukinumab

Phase 3

Completed

Conditions: Palmoplantar Pustular Psoriasis

Interventions: Biological: Secukinumab 300mg
Biological: Placebo
Biological: Secukinumab 150mg

Registration Number: NCT02008890

Lead Sponsor: Novartis Pharmaceuticals

Brief Summary: 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

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 237

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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Secukinumab 150mg	Placebo	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.
Secukinumab 300mg	Secukinumab 300mg	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.
Placebo	Secukinumab 300mg	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.
Secukinumab 300mg	Placebo	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.
Placebo	Secukinumab 150mg	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.
Placebo	Placebo	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.
Secukinumab 150mg	Secukinumab 150mg	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.

Primary Outcome Measures

Name	Time	Method
Percentage of Participants With ppPASI 75 Response at Week 16 (Period 1)	Baseline to Week 16	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.

Secondary Outcome Measures

Name	Time	Method
Percentage of Participants With ppPASI 75 Response Over Time (Period 1)	Baseline to Week 16	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.
Percentage of Participants With Most Frequent Adverse Events - Period 2 (Patient's Safety)	Week 16 to Week 52 (Period 2)	Most frequent (at least 5% in any of the AIN457 groups) Adverse Events
Percentage of Participants With ppPASI 75 Response Over Time (Extension Period)	Week 52 to Week 148	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.
ppPASI: Absolute Change From Baseline to Week 16	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.
Percentage of Participants With ppPASI 75 Response Over Time (Period 2)	Week 16 to Week 52	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.
Percentage of Participants With Most Frequent Adverse Events - Period 1 (Patient's Safety)	Baseline to Week 16 (Period 1)	Most frequent (at least 5% in any of the AIN457 groups) Adverse Events
Percentage of Participants With Most Frequent Adverse Events - Extension Period (Patient's Safety)	Week 52 to Week 148 (extension period)	Most frequent (at least 5% in any of the AIN457 groups) Adverse Events