4 Year Extension Study of Efficacy and Safety of Secukinumab in Patients With Moderate to Severe Chronic Plaque-type Psoriasis

A Multicenter, Double-blind and Open Label, 4 Year Extension Study of Subcutaneous Secukinumab in Prefilled Syringes, Assessing Long-term Safety, Tolerability and Efficacy in Subjects With Moderate to Severe Chronic Plaque-type Psoriasis Treated With Either a Fixed Dose Regimen or on a Retreatment at Start of Relapse Regimen

CAIN457A2304E1 was an extension study to two phase III studies, CAIN457A2304 and CAIN457A2307 (core studies). This extension study planned to collect up to four years of long-term safety, tolerability and efficacy data of secukinumab in both the fixed interval regimen and the retreatment at start of relapse regimen. All subjects who completed the full study treatment period (52 weeks) in the cores studies CAIN457A2304 and CAIN457A2307 were eligible to participate in this extension study. In this extension study, the prefilled syringe (PFS) liquid formulation of secukinumab was used.

Study Overview

• Status: Completed
• Conditions: Moderate to Severe Chronic Plaque-Type Psoriasis
• Intervention / Treatment: Drug: Placebo; Drug: AIN457 150 mg; Drug: AIN457 300 mg

• Study Type: Interventional
• Enrollment (Actual): 675
• Phase: Phase 3

Contacts and Locations

Study Locations

• Austria
  • Wels, Austria, 4600
    • Novartis Investigative Site
• Bulgaria
  • Pleven, Bulgaria, 5800
    • Novartis Investigative Site
  • Sofia, Bulgaria, 1431
    • Novartis Investigative Site
  • Sofia, Bulgaria, 1404
    • Novartis Investigative Site
  • Sofia, Bulgaria, 1231
    • Novartis Investigative Site
  • Varna, Bulgaria, 9010
    • Novartis Investigative Site
• Canada
  • Ontario
    • Barrie, Ontario, Canada, L4M 6L2
      • Novartis Investigative Site
    • Oakville, Ontario, Canada, L6J 7W5
      • Novartis Investigative Site
    • Waterloo, Ontario, Canada, N2J 1C4
      • Novartis Investigative Site
    • Windsor, Ontario, Canada, N8W 1E6
      • Novartis Investigative Site
  • Quebec
    • Montreal, Quebec, Canada, H2K 4L5
      • Novartis Investigative Site
• Czechia
  • Ceske Budejovice, Czechia, 370 01
    • Novartis Investigative Site
  • Novy Jicin, Czechia, 741 01
    • Novartis Investigative Site
  • Prague 10, Czechia, 100 34
    • Novartis Investigative Site
  • CZE
    • Hradec Kralove, CZE, Czechia, 500 05
      • Novartis Investigative Site
    • Prague 8, CZE, Czechia, 180 81
      • Novartis Investigative Site
  • Czech Republic
    • Brno - Bohunice, Czech Republic, Czechia, 625 00
      • Novartis Investigative Site
• France
  • Antony, France, 92160
    • Novartis Investigative Site
  • Nice Cedex 3, France, 06202
    • Novartis Investigative Site
  • Pierre-Benite Cedex, France, 69495
    • Novartis Investigative Site
  • Rouen, France, 76031
    • Novartis Investigative Site
  • Toulouse Cedex, France, 31400
    • Novartis Investigative Site
• Germany
  • Bad Wildbad, Germany, 75323
    • Novartis Investigative Site
  • Bochum, Germany, 44793
    • Novartis Investigative Site
  • Buchholz I. D. Nordheide, Germany, 21244
    • Novartis Investigative Site
  • Dippoldiswalde-Schmiedeberg, Germany, 01744
    • Novartis Investigative Site
  • Duesseldorf, Germany, D-40225
    • Novartis Investigative Site
  • Duisburg, Germany, 47166
    • Novartis Investigative Site
  • Essen, Germany, 45147
    • Novartis Investigative Site
  • Frankfurt, Germany, 60590
    • Novartis Investigative Site
  • Freiburg, Germany, 79104
    • Novartis Investigative Site
  • Hamburg, Germany, 20246
    • Novartis Investigative Site
  • Hamburg, Germany, 22143
    • Novartis Investigative Site
  • Hamburg, Germany, 22391
    • Novartis Investigative Site
  • Hannover, Germany, 30625
    • Novartis Investigative Site
  • Kiel, Germany, 24105
    • Novartis Investigative Site
  • Luebeck, Germany, 23538
    • Novartis Investigative Site
  • Mahlow, Germany, 15831
    • Novartis Investigative Site
  • Mainz, Germany, 55131
    • Novartis Investigative Site
  • Muenster, Germany, 48149
    • Novartis Investigative Site
  • Wuppertal, Germany, 42103
    • Novartis Investigative Site
  • Nordrhein-Westfalen
    • Koeln, Nordrhein-Westfalen, Germany, 50937
      • Novartis Investigative Site
• Italy
  • RM
    • Roma, RM, Italy, 00144
      • Novartis Investigative Site
    • Roma, RM, Italy, 00133
      • Novartis Investigative Site
  • SI
    • Siena, SI, Italy, 53100
      • Novartis Investigative Site
  • VR
    • Verona, VR, Italy, 37126
      • Novartis Investigative Site
• Japan
  • Aichi
    • Nagoya-city, Aichi, Japan, 467-8602
      • Novartis Investigative Site
  • Chiba
    • Kisarazu, Chiba, Japan, 292-8535
      • Novartis Investigative Site
  • Fukuoka
    • Fukuoka-city, Fukuoka, Japan, 815-8588
      • Novartis Investigative Site
    • Kitakyushu-city, Fukuoka, Japan, 800-0296
      • Novartis Investigative Site
  • Gunma
    • Maebashi city, Gunma, Japan, 371 8511
      • Novartis Investigative Site
  • Hokkaido
    • Asahikawa-city, Hokkaido, Japan, 078-8510
      • Novartis Investigative Site
    • Sapporo-city, Hokkaido, Japan, 060-0033
      • Novartis Investigative Site
  • Osaka
    • Osaka-city, Osaka, Japan, 550-0012
      • Novartis Investigative Site
  • Tochigi
    • Shimotsuke-city, Tochigi, Japan, 329-0498
      • Novartis Investigative Site
  • Tokyo
    • Chiyoda-ku, Tokyo, Japan, 102-8798
      • Novartis Investigative Site
    • Hachioji-city, Tokyo, Japan, 193-0944
      • Novartis Investigative Site
    • Itabashi-ku, Tokyo, Japan, 173-8610
      • Novartis Investigative Site
    • Minato-ku, Tokyo, Japan, 105-8471
      • Novartis Investigative Site
    • Shinjuku-ku, Tokyo, Japan, 160-0023
      • Novartis Investigative Site
    • Shinjuku-ku, Tokyo, Japan, 160-8582
      • Novartis Investigative Site
• Poland
  • Lodz, Poland, 90-265
    • Novartis Investigative Site
  • Poznan, Poland, 60 529
    • Novartis Investigative Site
  • Wroclaw, Poland, 50-368
    • Novartis Investigative Site
• Singapore
  • Singapore, Singapore, 119074
    • Novartis Investigative Site
  • Singapore, Singapore, 308205
    • Novartis Investigative Site
• Slovakia
  • Kosice, Slovakia, 04011
    • Novartis Investigative Site
  • Poprad, Slovakia, 05845
    • Novartis Investigative Site
  • Svidnik, Slovakia, 089 01
    • Novartis Investigative Site
  • Zilina, Slovakia, 01207
    • Novartis Investigative Site
  • Slovak Republic
    • Kosice, Slovak Republic, Slovakia, 040 15
      • Novartis Investigative Site
• Switzerland
  • Bern, Switzerland, 3010
    • Novartis Investigative Site
  • Lausanne, Switzerland, 1011
    • Novartis Investigative Site
  • Zuerich, Switzerland, 8091
    • Novartis Investigative Site
• United Kingdom
  • Birmingham, United Kingdom, B15 2WB
    • Novartis Investigative Site
  • Blackpool, United Kingdom, FY3 7EN
    • Novartis Investigative Site
  • Leicester, United Kingdom, LE7 5WW
    • Novartis Investigative Site
  • Poole, United Kingdom, BH15 2JB
    • Novartis Investigative Site
  • London
    • Leytonstone, London, United Kingdom, E11 1NR
      • Novartis Investigative Site
• United States
  • California
    • Fresno, California, United States, 93710
      • Novartis Investigative Site
    • Pasadena, California, United States, 91105
      • Novartis Investigative Site
    • San Francisco, California, United States, 94118
      • Novartis Investigative Site
  • Florida
    • Jacksonville, Florida, United States, 32204
      • Novartis Investigative Site
    • Jacksonville, Florida, United States, 32216
      • Novartis Investigative Site
    • Miami, Florida, United States, 33136
      • Novartis Investigative Site
    • South Miami, Florida, United States, 33143
      • Novartis Investigative Site
    • West Palm Beach, Florida, United States, 33409
      • Novartis Investigative Site
  • Georgia
    • Atlanta, Georgia, United States, 30342
      • Novartis Investigative Site
  • Illinois
    • Champaign, Illinois, United States, 61820
      • Novartis Investigative Site
    • Skokie, Illinois, United States, 60077
      • Novartis Investigative Site
  • Indiana
    • Indianapolis, Indiana, United States, 46256
      • Novartis Investigative Site
  • Kansas
    • Overland Park, Kansas, United States, 66215
      • Novartis Investigative Site
  • Massachusetts
    • Boston, Massachusetts, United States, 02111
      • Novartis Investigative Site
  • Minnesota
    • Fridley, Minnesota, United States, 55432
      • Novartis Investigative Site
  • Missouri
    • Saint Louis, Missouri, United States, 63117
      • Novartis Investigative Site
  • Nevada
    • Henderson, Nevada, United States, 89052
      • Novartis Investigative Site
    • Las Vegas, Nevada, United States, 89119
      • Novartis Investigative Site
  • New Jersey
    • Verona, New Jersey, United States, 07044
      • Novartis Investigative Site
  • North Carolina
    • Greensboro, North Carolina, United States, 27401
      • Novartis Investigative Site
    • High Point, North Carolina, United States, 27262
      • Novartis Investigative Site
    • Winston-Salem, North Carolina, United States, 27103
      • Novartis Investigative Site
  • South Carolina
    • Anderson, South Carolina, United States, 29621
      • Novartis Investigative Site
    • Greer, South Carolina, United States, 29651
      • Novartis Investigative Site
  • Tennessee
    • Goodlettsville, Tennessee, United States, 37072-2301
      • Novartis Investigative Site
  • Texas
    • Dallas, Texas, United States, 75231
      • Novartis Investigative Site
    • San Antonio, Texas, United States, 78229
      • Novartis Investigative Site
  • Utah
    • Salt Lake City, Utah, United States, 84124
      • Novartis Investigative Site
• Vietnam
  • Hanoi, Vietnam, 100000
    • Novartis Investigative Site
  • Hanoi, Vietnam, 1000
    • Novartis Investigative Site
  • Ho Chi Minh, Vietnam, 7000
    • Novartis Investigative Site
  • VNM
    • Ho Chi Minh, VNM, Vietnam, 700000
      • Novartis Investigative Site

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Subjects must be able to understand and communicate with the investigator and comply with the requirements of the study and must give a written, signed and dated informed consent before any study related activity is performed. Where relevant, a legal representative will also sign the informed consent according to local laws and regulations.
2. Subjects who complete Week 52 of study CAIN457A2304 or complete Week 40 of study CAIN457A2307
3. Subjects expected to benefit from participation in the extension study, as assessed by the subject and investigator

Exclusion Criteria:

1. A protocol deviation in the core studies which according to the investigator will prevent the meaningful analysis of the extension study for the individual subject
2. Ongoing use of prohibited psoriasis or non-psoriasis treatments. Time period from last use of prohibited treatments in the core study to first dose of study drug in this extension study.
3. Subjects expected to be exposed to an undue safety risk if participating in the trial
4. Current severe progressive or uncontrolled disease which in the judgment of the investigator renders the subject unsuitable for the trial
5. Plans for administration of live vaccines during the study period
6. Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive hCG laboratory test (>10 mIU/mL).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: AIN457 150 mg - Fixed Interval (FI); 1 s.c. Secukinumab 150 mg Pre-filled seringue (PFS) injection + 1 s.c. Placebo (PBO) Secukinumab PFS injection every 4 weeks	Drug: Placebo; Drug: AIN457 150 mg; (1 injection per dose) and placebo to Secukinumab 150 mg; Other Names: Secukinumab 150 mg
Experimental: AIN457 150 mg - Start of relapse (SoR); Start of relapse: 1 s.c. Secukinumab 150 mg PFS injection + 1 s.c. PBO Secukinumab PFS injection every 4 weeks Otherwise: 2 s.c. PBO Secukinumab PFS injections every 4 weeks	Drug: Placebo; Drug: AIN457 150 mg; (1 injection per dose) and placebo to Secukinumab 150 mg; Other Names: Secukinumab 150 mg
Experimental: AIN457 300 mg - Fixed Interval (FI); 2 s.c. Secukinumab 150 mg PFS injections every 4 weeks	Drug: AIN457 300 mg; Secukinumab 150 mg (2 injections per dose); Other Names: Secukinumab 300 mg
Experimental: AIN457 300 mg - Start of Relapse (SoR); Start of relapse: 2 s.c. Secukinumab 150 mg PFS injection every 4 weeks Otherwise: 2 s.c. PBO Secukinumab PFS injections every 4 weeks	Drug: Placebo; Drug: AIN457 300 mg; Secukinumab 150 mg (2 injections per dose); Other Names: Secukinumab 300 mg
Experimental: AIN457 300 mg - Open Label (OL); Open Label - Secukinumab 300mg every 4 weeks	Drug: AIN457 300 mg; Secukinumab 150 mg (2 injections per dose); Other Names: Secukinumab 300 mg

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Long-term Safety and Tolerability of Secukinumab	Analysis of absolute and relative frequencies for treatment emergent Adverse Event (AE), Serious Adverse Event (SAE) and Deaths by primary System Organ Class (SOC)	Week 268

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Achieving Psoriasis Area and Severity Index (PASI) Score of 75 at Weeks 52, 104, 156, 208 and 260	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 52, Week 104, Week 156, Week 208, Week 260
Percentage of Participants Achieving Psoriasis Area and Severity Index (PASI) Scores of 50, 90 and 100 Over Time at Weeks 52, 104, 156, 208 and 260	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 52, Week 104, Week 156, Week 208, Week 260
Percent Change From Baseline in Psoriasis Area and Severity Index (PASI) Score at Weeks 52, 104, 156, 208 and 260	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)	Baseline, Week 52, Week 104, Week 156, Week 208, Week 260
Percentage of Participants Achieving Investigator's Global Assessment Modified 2011 (IGA) 2011 Score of 0 or 1 Over Time at Weeks 52, 104, 156, 208 and 260	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.	Week 52, Week 104, Week 156, Week 208, Week 260
Percentage Change From Baseline in Dermatology Life Quality Index (DLQI©) Response at Weeks 52, 104, 156, 208 and 260	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, Week 52, Week 104, Week 156, Week 208, Week 260
Percentage of Participants With Dermatology Life Quality Index (DLQI©) Response (DLQI 0 or 1) Over Time at Weeks 52, 104, 156, 208 and 260	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	Week 52, Week 104, Week 156, Week 208, Week 260
EuroQOL 5-Dimension Health Status Questionnaire (EQ-5D©) Score and Percent Change From Baseline at Weeks 52, 104 and 156	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, Week 52, Week 104, Week 156
Number of Participants With Treatment Emergent Anti-drug Antibodies (ADA)	The development of anti-secunimubab anti-bodies will decrease a participant's ability to respond to secukinumab treatment.	Week 268
Percentage of Patients With Experiencing a Relapse	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 260
Percentage of Patients With Experiencing a Rebound	Rebound of disease is defined as a worsening of PASI of > 125% of the value at baseline (core study), or new pustular, erythrodermic or more inflammatory psoriasis occurring within 8 weeks of stopping therapy (i.e., if this definition was fulfilled at more than 8 weeks after last study treatment administration, this was defined as rebound like event). 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.	Up to Week 264 (8 weeks post last dose)

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Publications and helpful links

General Publications

• Bissonnette R, Luger T, Thaci D, Toth D, Messina I, You R, Guana A, Fox T, Papavassilis C, Gilloteau I, Mrowietz U. Secukinumab sustains good efficacy and favourable safety in moderate-to-severe psoriasis after up to 3 years of treatment: results from a double-blind extension study. Br J Dermatol. 2017 Oct;177(4):1033-1042. doi: 10.1111/bjd.15706. Epub 2017 Sep 4.

Study record dates

Study Major Dates

• Study Start (Actual): September 16, 2012
• Primary Completion (Actual): May 4, 2017
• Study Completion (Actual): May 4, 2017

Study Registration Dates

• First Submitted: July 12, 2012
• First Submitted That Met QC Criteria: July 13, 2012
• First Posted (Estimate): July 16, 2012

Study Record Updates

• Last Update Posted (Actual): May 25, 2018
• Last Update Submitted That Met QC Criteria: April 24, 2018
• Last Verified: April 1, 2018

More Information

Terms related to this study

• Keywords: Psoriasis; Plaque; Secukinumab; AIN457; Inflammatory skin disease; Moderate to Severe Plaque-type Psoriasis; Scaly patches
• Additional Relevant MeSH Terms: Skin Diseases; Skin Diseases, Papulosquamous; Psoriasis; Physiological Effects of Drugs; Immunologic Factors; Antibodies, Monoclonal
• Other Study ID Numbers: CAIN457A2304E1; 2012-000985-39 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

IPD 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

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No