Palmoplantar Pustular Psoriasis Efficacy and Safety With Secukinumab

• ClinicalTrials.gov Identifier: NCT02008890
• Recruitment Status: Completed
• First Posted: December 11, 2013
• Results First Posted: January 4, 2019
• Last Update Posted: January 4, 2019
• Sponsor: Novartis Pharmaceuticals
• Information provided by (Responsible Party): Novartis ( Novartis Pharmaceuticals )

Study Description

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

Condition or disease	Intervention/treatment	Phase
Palmoplantar Pustular Psoriasis	Biological: Secukinumab 300mg; Biological: Secukinumab 150mg; Biological: Placebo	Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 237 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: 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
• Actual Study Start Date: December 26, 2013
• Actual Primary Completion Date: November 24, 2014
• Actual Study Completion Date: May 31, 2017

Arms and Interventions

Arm	Intervention/treatment
Experimental: 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.	Biological: Secukinumab 300mg; 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; Biological: Placebo; secukinumab placebo s.c. (two PFS injections of placebo) self-administered
Experimental: 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.	Biological: Secukinumab 150mg; secukinumab 150 mg s.c. (one PFS injection of the 150 mg dose + one PFS injection of placebo) self-administered; Biological: Placebo; secukinumab placebo s.c. (two PFS injections of placebo) self-administered
Placebo Comparator: 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.	Biological: Secukinumab 300mg; 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; Biological: Secukinumab 150mg; secukinumab 150 mg s.c. (one PFS injection of the 150 mg dose + one PFS injection of placebo) self-administered; Biological: Placebo; secukinumab placebo s.c. (two PFS injections of placebo) self-administered

Outcome Measures

Primary Outcome Measures :

1. Percentage of Participants With ppPASI 75 Response at Week 16 (Period 1) [ Time Frame: 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 :

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

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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.

Contacts and Locations

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Locations

Austria

Novartis Investigative Site

Feldkirch, Austria, A-6807

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Graz, Austria, 8036

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Linz, Austria, A-4020

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Wien, Austria, 1090

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Wien, Austria, A-1090

Belgium

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Bruxelles, Belgium, 1200

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Gent, Belgium, 9000

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Leuven, Belgium, 3000

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Liege, Belgium, 4000

France

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Limoges cedex, Haute Vienne, France, 87000

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Bordeaux Cedex, France, 33075

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Clermont Ferrand cedex 1, France, 63003

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Martigues, France, 13500

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Nice Cedex 3, France, 06202

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Paris, France, 75010

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Paris, France, 75014

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Poitiers, France, 86021

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Rouen, France, 76031

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Toulouse Cedex, France, 31400

Germany

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Berlin, Germany, 10827

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Bochum, Germany, 44803

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Dresden, Germany, 01307

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Duesseldorf, Germany, D 40225

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Freiburg, Germany, 79104

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Gera, Germany, 07548

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Gottingen, Germany, 37075

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Greifswald, Germany, 17475

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Hamburg, Germany, 20354

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Hamburg, Germany, 22391

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Hanau, Germany, 63450

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Kiel, Germany, 24105

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Lubeck, Germany, 23538

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Mahlow, Germany, 15831

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Muenster, Germany, 48149

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Plauen, Germany, 08529

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Recklinghausen, Germany, 45657

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Schwerin, Germany, 19055

Italy

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Bologna, BO, Italy, 40138

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Brescia, BS, Italy, 25123

Poland

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Bydgoszcz, Poland, 85-094

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Gdansk, Poland, 80-803

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Olsztyn, Poland, 10-045

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Zabrze, Poland, 41-800

Russian Federation

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Moscow, Russian Federation, 107076

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Rostov on Don region, Russian Federation, 346880

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Ryazan, Russian Federation, 390046

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Saratov, Russian Federation, 410012

Spain

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Valencia, Comunidad Valenciana, Spain, 46014

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La Laguna, Santa Cruz De Tenerife, Spain, 38320

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A Coruna, Spain, 15001

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Barcelona, Spain, 08041

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Madrid, Spain, 28006

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Madrid, Spain, 28031

Sweden

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Göteborg, Vastra Gotalands Lan, Sweden, SE-413 45

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Joenkoeping, Sweden, 551 85

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Malmo, Sweden, SE-205 02

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Stockholm, Sweden, 171 76

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Uppsala, Sweden, 751 85

United Kingdom

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Leytonstone, London, United Kingdom, E11 1NR

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Salford, Manchester, United Kingdom, M6 8HD

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Dundee, Perthshire, United Kingdom, DD1 9SY

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Dudley, West Midlands, United Kingdom, DY1 2HQ

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Glasgow, United Kingdom, G11 6NT

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Liverpool, United Kingdom, L14 3PE

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Newport, United Kingdom, NP20 4SZ

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Portsmouth, United Kingdom, PO6 6AD

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Wolverhampton, United Kingdom, WV10 0QP

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York, United Kingdom, YO31 8HE

Sponsors and Collaborators

Novartis Pharmaceuticals

Investigators

• Study Director: Novartis Pharmaceuticals; Novartis Pharmaceuticals

More Information

• Responsible Party: Novartis Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT02008890 History of Changes
• Other Study ID Numbers: CAIN457A3301; 2013-003086-34 ( EudraCT Number )
• First Posted: December 11, 2013
• Results First Posted: January 4, 2019
• Last Update Posted: January 4, 2019
• Last Verified: January 2019

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided

Plan Description

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com

Keywords provided by Novartis ( Novartis Pharmaceuticals ):

palmoplantar, pustular, psoriasis

Additional relevant MeSH terms:

Psoriasis; Skin Diseases, Papulosquamous; Skin Diseases; Antibodies, Monoclonal; Immunologic Factors; Physiological Effects of Drugs