Efficacy and Safety of Subcutaneous Secukinumab (AIN457) for Moderate to Severe Chronic Plaque-type Psoriasis Assessing Different Doses and Dose Regimens

Moderate to Severe Plaque-type Psoriasis Clinical Trial

— SCULPTURE  

Official title:

A Randomized, Double-blind, Multicenter Study of Subcutaneous Secukinumab, Assessing Psoriasis Area and Severity Index (PASI) Response and Maintenance of Response in Subjects With Moderate to Severe Chronic Plaque-type Psoriasis on Either a Fixed Dose Regimen or on a Retreatment at Start of Relapse Regimen

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01406938
• Other study ID #: CAIN457A2304
• Secondary ID: 2011-000767-27
• Status: Completed
• Phase: Phase 3
• First received: July 12, 2011
• Last updated: April 30, 2015
• Start date: August 2011
• Est. completion date: May 2013

Study information

• Verified date: April 2015
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationAustria: Federal Ministry for Health and WomenBulgaria: Bulgarian Drug AgencyCanada: Health CanadaCzech Republic: State Institute for Drug ControlFrance: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)Germany: Paul-Ehrlich-InstitutIndia: Drugs Controller General of IndiaItaly: The Italian Medicines AgencyJapan: Ministry of Health, Labor and WelfarePeru: Instituto Nacional de SaludPoland: Office for Registration of Medicinal Products, Medical Devices and Biocidal ProductsSingapore: Health Sciences AuthoritySlovakia: State Institute for Drug ControlSwitzerland: SwissmedicTaiwan: Department of HealthUnited Kingdom: Medicines and Healthcare Products Regulatory AgencyVietnam: Ministry of Health
• Study type: Interventional

Clinical Trial Summary

This study will assess the safety and efficacy of two different doses and two different dose regimens of subcutaneous secukinumab in patients that have moderate to severe, chronic, plaque-type psoriasis.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 967
• Est. completion date: May 2013
• Est. primary completion date: May 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion criteria:

• Moderate and severe plaque-type psoriasis diagnosed for at least 6 months.

Severity of disease meeting all of the following three criteria:

• PASI score of 12 or greater,

• Investigator's Global Assessment (IGA) score of 3 or greater

• Total body surface area (BSA) affected of 10% or greater.

• Inadequate control by prior use of topical treatment, phototherapy and/or systemic therapy.

Exclusion criteria:

• Current forms of psoriasis other than chronic plaque-type psoriasis (for example, pustular, erythrodermic, guttate).

• Current drug-induced psoriasis.

• Previous use of secukinumab or any drug that targets IL-17 or IL-17 receptor.

• Significant medical problems such as uncontrolled hypertension, congestive heart failure or a condition that significantly immunocompromises the subject.

• Hematological abnormalities.

• History of an ongoing, chronic or recurrent infectious disease, or evidence of untreated tuberculosis.

• History of lymphoproliferative disease or history of malignancy of any organ system within the past 5 years.

• Pregnant or nursing (lactating) women.

• Other protocol-defined inclusion/exclusion criteria may apply.

Study Design

Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Moderate to Severe Plaque-type Psoriasis
• Psoriasis

Intervention

Drug:
• AIN457 150mg
(1 injection per dose) and placebo to secukinumab 150 mg
• AIN457 300mg
secukinumab 150 mg (2 injections per dose)

Locations

Country	Name	City	State
Austria	Novartis Investigative Site	Graz
Austria	Novartis Investigative Site	Linz
Austria	Novartis Investigative Site	Vienna
Austria	Novartis Investigative Site	Wels
Bulgaria	Novartis Investigative Site	Pleven
Bulgaria	Novartis Investigative Site	Sofia
Bulgaria	Novartis Investigative Site	Sofia
Bulgaria	Novartis Investigative Site	Sofia
Bulgaria	Novartis Investigative Site	Sofia
Bulgaria	Novartis Investigative Site	Varna
Canada	Novartis Investigative Site	Barrie	Ontario
Canada	Novartis Investigative Site	Montreal	Quebec
Canada	Novartis Investigative Site	Oakville	Ontario
Canada	Novartis Investigative Site	Waterloo	Ontario
Canada	Novartis Investigative Site	Windsor	Ontario
Czech Republic	Novartis Investigative Site	Brno - Bohunice
Czech Republic	Novartis Investigative Site	Ceske Budejovice
Czech Republic	Novartis Investigative Site	Hradec Kralove	CZE
Czech Republic	Novartis Investigative Site	Novy Jicin
Czech Republic	Novartis Investigative Site	Prague 10
Czech Republic	Novartis Investigative Site	Prague 8	CZE
France	Novartis Investigative Site	Antony
France	Novartis Investigative Site	Nice Cedex 3
France	Novartis Investigative Site	Pierre-Benite Cédex
France	Novartis Investigative Site	Rouen
France	Novartis Investigative Site	Toulouse Cedex
Germany	Novartis Investigative Site	Bad Wildbad
Germany	Novartis Investigative Site	Bochum
Germany	Novartis Investigative Site	Buchholz i. d. Nordheide
Germany	Novartis Investigative Site	Dippoldiswalde-Schmiedeberg
Germany	Novartis Investigative Site	Duisburg
Germany	Novartis Investigative Site	Düsseldorf
Germany	Novartis Investigative Site	Essen
Germany	Novartis Investigative Site	Frankfurt
Germany	Novartis Investigative Site	Freiburg
Germany	Novartis Investigative Site	Hamburg
Germany	Novartis Investigative Site	Hamburg
Germany	Novartis Investigative Site	Hamburg
Germany	Novartis Investigative Site	Hannover
Germany	Novartis Investigative Site	Kiel
Germany	Novartis Investigative Site	Köln
Germany	Novartis Investigative Site	Luebeck
Germany	Novartis Investigative Site	Mahlow
Germany	Novartis Investigative Site	Mainz
Germany	Novartis Investigative Site	Mannheim
Germany	Novartis Investigative Site	Muenster
Germany	Novartis Investigative Site	Pommelsbrunn
Germany	Novartis Investigative Site	Wuppertal
India	Novartis Investigative Site	Bangalore	Karnataka
India	Novartis Investigative Site	Hyderabad	Andhra Pradesh
India	Novartis Investigative Site	Mangalore	Karnataka
India	Novartis Investigative Site	Mumbai	Maharashtra
India	Novartis Investigative Site	Nagpur	Maharashtra
India	Novartis Investigative Site	Nagpur	Maharashtra
India	Novartis Investigative Site	Nagpur	Maharashtra
India	Novartis Investigative Site	Nashik	Maharashtra
India	Novartis Investigative Site	Secunderabad	Andhra Pradesh
Italy	Novartis Investigative Site	Roma	RM
Italy	Novartis Investigative Site	Roma	RM
Italy	Novartis Investigative Site	Siena	SI
Italy	Novartis Investigative Site	Verona	VR
Japan	Novartis Investigative Site	Asahikawa-city	Hokkaido
Japan	Novartis Investigative Site	Chiyoda-ku	Tokyo
Japan	Novartis Investigative Site	Fukuoka-city	Fukuoka
Japan	Novartis Investigative Site	Hachioji-city	Tokyo
Japan	Novartis Investigative Site	Itabashi-ku	Tokyo
Japan	Novartis Investigative Site	Kisarazu	Chiba
Japan	Novartis Investigative Site	Kitakyushu-city	Fukuoka
Japan	Novartis Investigative Site	Maebashi-city	Gunma
Japan	Novartis Investigative Site	Minato-ku	Tokyo
Japan	Novartis Investigative Site	Nagoya-city	Aichi
Japan	Novartis Investigative Site	Osaka-city	Osaka
Japan	Novartis Investigative Site	Sapporo-city	Hokkaido
Japan	Novartis Investigative Site	Shimotsuke-city	Tochigi
Japan	Novartis Investigative Site	Shinjuku-ku	Tokyo
Japan	Novartis Investigative Site	Shinjuku-ku	Tokyo
Poland	Novartis Investigative Site	Lodz
Poland	Novartis Investigative Site	Poznan
Poland	Novartis Investigative Site	Wroclaw
Singapore	Novartis Investigative Site	Singapore
Singapore	Novartis Investigative Site	Singapore
Slovakia	Novartis Investigative Site	Bratislava
Slovakia	Novartis Investigative Site	Kosice
Slovakia	Novartis Investigative Site	Kosice	Slovak Republic
Slovakia	Novartis Investigative Site	Poprad
Slovakia	Novartis Investigative Site	Svidnik
Slovakia	Novartis Investigative Site	Zilina
Switzerland	Novartis Investigative Site	Bern
Switzerland	Novartis Investigative Site	Lausanne
Switzerland	Novartis Investigative Site	Zuerich
United Kingdom	Novartis Investigative Site	Birmingham
United Kingdom	Novartis Investigative Site	Blackpool
United Kingdom	Novartis Investigative Site	Leicester
United Kingdom	Novartis Investigative Site	London	England
United Kingdom	Novartis Investigative Site	Poole
United States	Novartis Investigative Site	Anderson	South Carolina
United States	Novartis Investigative Site	Atlanta	Georgia
United States	Novartis Investigative Site	Boston	Massachusetts
United States	Novartis Investigative Site	Champaign	Illinois
United States	Novartis Investigative Site	Dallas	Texas
United States	Novartis Investigative Site	Dallas	Texas
United States	Novartis Investigative Site	Fresno	California
United States	Novartis Investigative Site	Fridley	Minnesota
United States	Novartis Investigative Site	Goodlettsville	Tennessee
United States	Novartis Investigative Site	Greensboro	North Carolina
United States	Novartis Investigative Site	Greer	South Carolina
United States	Novartis Investigative Site	Henderson	Nevada
United States	Novartis Investigative Site	High Point	North Carolina
United States	Novartis Investigative Site	Indianapolis	Indiana
United States	Novartis Investigative Site	Jacksonville	Florida
United States	Novartis Investigative Site	Jacksonville	Florida
United States	Novartis Investigative Site	Las Vegas	Nevada
United States	Novartis Investigative Site	Miami	Florida
United States	Novartis Investigative Site	Naples	Florida
United States	Novartis Investigative Site	Overland Park	Kansas
United States	Novartis Investigative Site	Owensboro	Kentucky
United States	Novartis Investigative Site	Pasadena	California
United States	Novartis Investigative Site	Sacramento	California
United States	Novartis Investigative Site	Salt Lake City	Utah
United States	Novartis Investigative Site	San Antonio	Texas
United States	Novartis Investigative Site	San Francisco	California
United States	Novartis Investigative Site	Skokie	Illinois
United States	Novartis Investigative Site	South Miami	Florida
United States	Novartis Investigative Site	Springfield	Illinois
United States	Novartis Investigative Site	St. Louis	Missouri
United States	Novartis Investigative Site	Verona	New Jersey
United States	Novartis Investigative Site	West Palm Beach	Florida
United States	Novartis Investigative Site	Winston-Salem	North Carolina
Vietnam	Novartis Investigative Site	Hanoi
Vietnam	Novartis Investigative Site	Ho Chi Minh

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

United States,  Vietnam,  Austria,  Bulgaria,  Canada,  Czech Republic,  France,  Germany,  India,  Italy,  Japan,  Poland,  Singapore,  Slovakia,  Switzerland,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	For the Fixed Interval Group and the Start of Relapse (SoR) Group, the Percentage of Participants (Who Responded to Treatment at Week 12) Maintaining a 75% Improvement From Baseline in Psoriasis Area and Severity Index (PASI) Score at Week 52	PASI: Combined assessment of lesion severity and affected area into a single score: 0 (no disease) to 72(maximal disease). Body is divided into 4 areas for scoring (head, arms, trunk, legs; each area is scored by itself and scores are combined for final PASI. For each area, percent of skin involved is estimated: 0 (0%) to 6 (90-100%), and severity is estimated by clinical signs, erythema, induration and desquamation; scale 0 (none) to 4 (maximum). Final PASI = sum of severity parameters for each area* area score weight of section(head: 0.1, arms: 0.2 body: 0.3 legs: 0.4)	Week 40 , week 52	No
Secondary	Absolute Change From Baseline for PASI 50 / 75 / 90 / 100 and IGA 2011 Score of 0 or 1 at Week 2, 4, 6, 8, 12	PASI: Combined assessment of lesion severity and affected area into a single score: 0 (no disease) to 72(maximal disease). Body is divided into 4 areas for scoring (head, arms, trunk, legs; each area is scored by itself and scores are combined for final PASI. For each area, percent of skin involved is estimated: 0 (0%) to 6 (90-100%), and severity is estimated by clinical signs, erythema, induration and desquamation; scale 0 (none) to 4 (maximum). Final PASI = sum of severity parameters for each area* area score weight of section(head:01, arms:0.2 body:0.3 legs:0.4)	Baseline, week 2, 3 , 4, 8, 12	No
Secondary	Absolute Change From Baseline for PASI 50 / 75 / 90 / 100 and IGA 2011 Score of 0 or 1 at Week at Week 16, 20, 24,28,32,36,40,44,48,and Week 52	PASI: Combined assessment of lesion severity and affected area into a single score: 0 (no disease) to 72(maximal disease). Body is divided into 4 areas for scoring (head, arms, trunk, legs; each area is scored by itself and scores are combined for final PASI. For each area, percent of skin involved is estimated: 0 (0%) to 6 (90-100%), and severity is estimated by clinical signs, erythema, induration and desquamation; scale 0 (none) to 4 (maximum). Final PASI = sum of severity parameters for each area* area score weight of section(head:01, arms:0.2 body:0.3 legs:0.4)	Baseline, week 12,16,20,24,28,32,36,40,44,48 and week 52	No
Secondary	Percent of Participants Achieving Psoriasis Area & Severity Index (PASI) Score and IGA Mod 2011 0 or 1 Score Over Time at Week 12 and 52 (Induction)	PASI is a combined assessment of lesion severity and affected area into a single score: 0 (no disease) to 72 (maximal disease). Body is divided into 4 areas for scoring (head, arms, trunk, legs; each area is scored by itself and scores are combined for final PASI. For each area, percent of skin involved is estimated: 0 (0%) to 6 (90-100%), and severity is estimated by clinical signs, erythema, induration and desquamation; scale 0 (none) to 4 (maximum). Final PASI = sum of severity parameters for each area* area score weight of section (head: 0.1, arms: 0.2 body: 0.3 legs: 0.4). PASI 50, 75, 90 and 100 were defined as participants achieving = 50%, 75%, 90% or 100% improvement from baseline. The IGA mod 2011 scale is static, i.e. it referred exclusively to the participant's disease at the time of the assessment, and did not compare with any of the participant's previous disease states at previous visits. The scores are: 0 = clear, 1 = almost clear, 2 = mild, 3 = moderate and 4 = severe	Baseline, week 2, 4, 6, 8, 12	No
Secondary	Percent of Participants Achieving Psoriasis Area & Severity Index (PASI) Score and IGA Mod 2011 0 or 1 Score Over Time at Week 12 and 52 (Maintenance Period))	The IGA mod 2011 is a static scale, i.e., it refers exclusively to the participant's disease state at the time of the assessments and does not attempt a comparison to any of the participant's previous disease states at prior visits. The score ranges from 0 (clear) to 4 (severe. The score 0 is clear, 1 is almost clear, 2 is mild, 3 is moderate, and 4 is severe	Baseline, week 16,20,24,28,32,36,40,44,48, and Week 52	No
Secondary	Change From Baseline in EQ-5D at Each Visit, up to Week 52, (Induction)	ED-5Q: Participant rated questionnaire to assess health related quality of life in terms of a single utility score. Five domains are assessed mobility, self-care, usual activities, pain/discomfort, and anxiety/depression) each with three possible score: 1 indicates no problems, better state of health; 3 indicates worst state of health (example "confined to bed") A visual analog scale (VAS) assesses the health status from 0 (worst possible health state) to 100 (best possible health state)	Baseline to week 2, 4, 8, 12	No
Secondary	Change From Baseline in EQ-5D at Each Visit, up to Week 52, (Maintenance)	ED-5Q: Participant rated questionnaire to assess health related quality of life in terms of a single utility score. Five domains are assessed mobility, self-care, usual activities, pain/discomfort, and anxiety/depression) each with three possible score: 1 indicates no problems, better state of health; 3 indicates worst state of health (example "confined to bed") A visual analog scale (VAS) assesses the health status from 0 (worst possible health state) to 100 (best possible health state)	Baseline to week 16, 20, 24, 28, 32, 36, 40, 44, 48, and Week 52.	No
Secondary	Change From Baseline in Dermatology Life Quality Index (DLQI) Score. up to Week 52, (Induction)	The DLQI is a quality of life measure used in the psoriatic The 10-item questionnaire has a score range of 0 (best) to 30 (worst) with higher scores indicating poor quality of life. The instrument contains six functional scales (i.e., symptoms and feeling, daily activities, leisure, work and school, personal relationships, treatment). Each item has 4 response categories, ranging from 0 (not at all) to 3 (very much). "Not relevant" is also a valid response and is scored as 0. The DLQI total score is a sum of the 10 questions	Baseline to week 2, 4, 8, 12	No
Secondary	Change From Baseline in Dermatology Life Quality Index (DLQI) Score. up to Week 52, (Maintenance)	The DLQI is a quality of life measure used in the psoriatic The 10-item questionnaire has a score range of 0 (best) to 30 (worst) with higher scores indicating poor quality of life. The instrument contains six functional scales (i.e., symptoms and feeling, daily activities, leisure, work and school, personal relationships, treatment). Each item has 4 response categories, ranging from 0 (not at all) to 3 (very much). "Not relevant" is also a valid response and is scored as 0. The DLQI total score is a sum of the 10 questions	Baseline to week 16, 20, 24, 28, 32, 36, 40, 44, 48, and Week 52.	No
Secondary	% of Participants Achieving a DLQI Score of 0 or 1 at Each Visit up to Week 52, (Induction)	The DLQI is a quality of life measure used in the psoriatic The 10-item questionnaire has a score range of 0 (best) to 30 (worst) with higher scores indicating poor quality of life. The instrument contains six functional scales (i.e., symptoms and feeling, daily activities, leisure, work and school, personal relationships, treatment). Each item has 4 response categories, ranging from 0 (not at all) to 3 (very much). "Not relevant" is also a valid response and is scored as 0. The DLQI total score is a sum of the 10 questions	Baseline to week 2, 4, 6, 8, 12	No
Secondary	% of Participants Achieving a DLQI Score of 0 or 1 at Each Visit up to Week 52, (Maintenance).	The DLQI is a quality of life measure used in the psoriatic The 10-item questionnaire has a score range of 0 (best) to 30 (worst) with higher scores indicating poor quality of life. The instrument contains six functional scales (i.e., symptoms and feeling, daily activities, leisure, work and school, personal relationships, treatment). Each item has 4 response categories, ranging from 0 (not at all) to 3 (very much). "Not relevant" is also a valid response and is scored as 0. The DLQI total score is a sum of the 10 questions	Baseline to week 16, 20, 24, 28, 32, 36, 40, 44, 48, and Week 52	No
Secondary	Median Time to Relapse (Weeks) From Week 12.	Median time to relapse (weeks) from week 12. Relapse is defined as greater than 50% loss of the maximal PASI improvement from baseline. PASI is a combined assessment of lesion severity and affected area into a single score: 0 (no disease) to 72(maximal disease). Body is divided into 4 areas for scoring (head, arms, trunk, legs; each area is scored by itself and scores are combined for final PASI. For each area, percent of skin involved is estimated: 0 (0%) to 6 (90-100%), and severity is estimated by clinical signs, erythema, induration and desquamation; scale 0 (none) to 4 (maximum). Final PASI = sum of severity parameters for each area* area score weight of section (head: 0.1, arms: 0.2 body: 0.3 legs: 0.4). A negative mean percentage change indicates improvement	Week 12 to week 16, 20, 24, 28, 32, 36, 40, 44, 48, and Week 52.	No
Secondary	Percent of Responders With PASI Equal to or Greater Than 50, PASI 75, PASI 90, PASI 100 and Percent of Responders With IGA Score of 0 or 1 Who Failed to Respond to a Previous Biologic Psoriasis Therapy	PASI is a combined assessment of lesion severity and affected area into a single score: 0 (no disease) to 72 (maximal disease). Body is divided into 4 areas for scoring (head, arms, trunk, legs; each area is scored by itself and scores are combined for final PASI. For each area, percent of skin involved is estimated: 0 (0%) to 6 (90-100%), and severity is estimated by clinical signs, erythema, induration and desquamation; scale 0 (none) to 4 (maximum). Final PASI = sum of severity parameters for each area* area score weight of section (head: 0.1, arms: 0.2 body: 0.3 legs: 0.4). PASI 50, 75, 90 and 100 were defined as participants achieving = 50%, 75%, 90% or 100% improvement from baseline. The IGA mod 2011 scale is static, i.e. it referred exclusively to the participant's disease at the time of the assessment, and did not compare with any of the participant's previous disease states at previous visits. The scores are: 0 = clear, 1 = almost clear, 2 = mild, 3 = moderate and 4 = severe.	Week 12	No
Secondary	Percent of Responders With PASI Equal to or Greater Than 50, PASI 75, PASI 90, PASI 100 and Percent of Responders With IGA Score of 0 or 1 Who Failed to Respond to a Previous Biologic Psoriasis Therapy	PASI is a combined assessment of lesion severity and affected area into a single score: 0 (no disease) to 72 (maximal disease). Body is divided into 4 areas for scoring (head, arms, trunk, legs; each area is scored by itself and scores are combined for final PASI. For each area, percent of skin involved is estimated: 0 (0%) to 6 (90-100%), and severity is estimated by clinical signs, erythema, induration and desquamation; scale 0 (none) to 4 (maximum). Final PASI = sum of severity parameters for each area* area score weight of section (head: 0.1, arms: 0.2 body: 0.3 legs: 0.4). PASI 50, 75, 90 and 100 were defined as participants achieving = 50%, 75%, 90% or 100% improvement from baseline. The IGA mod 2011 scale is static, i.e. it referred exclusively to the participant's disease at the time of the assessment, and did not compare with any of the participant's previous disease states at previous visits. The scores are: 0 = clear, 1 = almost clear, 2 = mild, 3 = moderate and 4 = severe.	Week 52	No
Secondary	Number of Visits With PASI 50, 75, 90, 100 Score and IGA Mod 2011 0 or 1	PASI is a combined assessment of lesion severity and affected area into a single score: 0 (no disease) to 72 (maximal disease). Body is divided into 4 areas for scoring (head, arms, trunk, legs; each area is scored by itself and scores are combined for final PASI. For each area, percent of skin involved is estimated: 0 (0%) to 6 (90-100%), and severity is estimated by clinical signs, erythema, induration and desquamation; scale 0 (none) to 4 (maximum). Final PASI = sum of severity parameters for each area* area score weight of section (head: 0.1, arms: 0.2 body: 0.3 legs: 0.4). PASI 50, 75, 90 and 100 were defined as participants achieving = 50%, 75%, 90% or 100% improvement from baseline. The IGA mod 2011 scale is static, i.e. it referred exclusively to the participant's disease at the time of the assessment, and did not compare with any of the participant's previous disease states at previous visits. The scores are: 0 = clear, 1 = almost clear, 2 = mild, 3 = moderate and 4 = severe.	Week 16, 20, 24,28,32,36,40,44,48,and Week 52	No
Secondary	Number of Secukinumab Injections Needed to Regain PASI 75 Response From Start of Relapse After Week 12	The number of secukinumab injections needed for participants to regain PASI 75 response from the start of relapse after week 12	week 16, 20, 24,28,32,36,40,44,48,and Week 52	No
Secondary	Number of Participants Developing Anti-secukinumab Antibodies	The development of anti-secunimubab anti-bodies will decrease a participant's ability to respond to secukinumab treatment. The number of participants developing anti-secukinumab anti-bodies was measured from Baseline to week 12, 24, 52 and 8 weeks after treatment at week 60	Baseline, weeks 12, 24, 52 and 60	No