Study of Efficacy and Safety of Secukinumab in Subjects With Moderate to Severe Chronic Plaque-type Psoriasis

A Randomized, Double-blind, Placebo Controlled, Multicenter Study of Subcutaneous Secukinumab, to Demonstrate Efficacy After Twelve Weeks of Treatment and to Assess Safety, Tolerability and Long-term Efficacy up to One Year in Subjects With Moderate to Severe Chronic Plaque-type Psoriasis With or Without Psoriatic Arthritis Comorbidity

The purpose of this study was to determine if secukinumab is effective and safe in the treatment of plaque type psoriasis

Study Overview

• Status: Completed
• Conditions: Plaque Psoriasis
• Intervention / Treatment: Drug: Secukinumab 150 mg s.c.; Drug: Secukinumab 300 mg s.c.; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 543
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Beijing, China, 100034
    • Novartis Investigative Site
  • Guang Zhou, China, 510080
    • Novartis Investigative Site
  • Guangzhou, China, 510000
    • Novartis Investigative Site
  • Nanjing, China, 210042
    • Novartis Investigative Site
  • Shanghai, China, 200433
    • Novartis Investigative Site
  • Shanghai, China, 200040
    • Novartis Investigative Site
  • Tianjin, China, 300052
    • Novartis Investigative Site
  • Beijing
    • Beijing, Beijing, China, 100039
      • Novartis Investigative Site
    • Xicheng Direct, Beijing, China, 100044
      • Novartis Investigative Site
  • Hubei
    • Wuhan, Hubei, China, 430030
      • Novartis Investigative Site
  • Jilin
    • Chang Chun, Jilin, China, 130021
      • Novartis Investigative Site
  • Liaoning
    • Dalian, Liaoning, China, 116011
      • Novartis Investigative Site
    • Shenyang, Liaoning, China, 110000
      • Novartis Investigative Site
  • Sichuan
    • Chengdu, Sichuan, China, 610041
      • Novartis Investigative Site
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310016
      • Novartis Investigative Site
    • Hangzhou, Zhejiang, China, 310009
      • Novartis Investigative Site
    • Hangzhou, Zhejiang, China, 310014
      • Novartis Investigative Site
• Hungary
  • Kaposvar, Hungary, 7400
    • Novartis Investigative Site
  • Oroshaza, Hungary, 5900
    • Novartis Investigative Site
  • Bacs Kiskun
    • Kecskemet, Bacs Kiskun, Hungary, 6000
      • Novartis Investigative Site
• Malaysia
  • Batu Caves, Malaysia, 68100
    • Novartis Investigative Site
  • Penang, Malaysia, 10990
    • Novartis Investigative Site
• Philippines
  • Makati City, Philippines, 1220
    • Novartis Investigative Site
  • Quezon City, Philippines, 1102
    • Novartis Investigative Site
• Thailand
  • Bangkok, Thailand, 10330
    • Novartis Investigative Site
  • Bangkok, Thailand, 10400
    • Novartis Investigative Site
  • Bangkok
    • Bangkoknoi, Bangkok, Thailand, 10700
      • Novartis Investigative Site
• Turkey
  • Aydin, Turkey, 09100
    • Novartis Investigative Site
  • Izmir, Turkey, 35340
    • Novartis Investigative Site
  • Manisa, Turkey, 45040
    • Novartis Investigative Site
  • Mersin, Turkey, 33079
    • Novartis Investigative Site
  • Pendik / Istanbul, Turkey, 34899
    • 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 give a written, signed and dated informed consent.
2. Men or women at least 18 years of age at time of screening.
3. Chronic plaque-type psoriasis present for at least 6 months and diagnosed before Baseline.

4. Moderate to severe psoriasis as defined at Baseline by:

   • PASI score of 12 or greater, and
   • IGA mod 2011 score of 3 or greater (based on a static scale of 0 - 4), and
   • Body Surface Area (BSA) affected by plaque-type psoriasis of 10% or greater.

5. Candidate for systemic therapy. This is defined as a subject having moderate to severe chronic plaque-type psoriasis that is inadequately controlled by

   • topical treatment and/or,
   • phototherapy and/or,
   • previous systemic therapy.

Exclusion Criteria:

1. Forms of psoriasis other than chronic plaque-type (e.g., pustular, erythrodermic and guttate psoriasis) at Screening or Baseline.
2. Drug-induced psoriasis.
3. Ongoing use of prohibited treatments.
4. Previous exposure to secukinumab (AIN457) or any other biologic drug directly targeting IL-17 or the IL-17 receptor.
5. Use of other investigational drugs at the time of enrollment, or within 5 half-lives of enrollment, or within 30 days until the expected pharmacodynamic effect has returned to baseline, whichever is longer; or longer if required by local regulations.
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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Secukinumab 150mg; Secukinumab 150mg s.c.	Drug: Secukinumab 150 mg s.c.; 150 mg s.c. at randomization, Weeks 1, 2, 3, 4 and every 4 weeks till Week 48
Experimental: Secukinumab 300mg; Secukinumab 300mg s.c.	Drug: Secukinumab 300 mg s.c.; 300 mg s.c. at randomization, Weeks 1, 2, 3, 4 and every 4 weeks till Week 48
Placebo Comparator: Placebo; Placebo to secukinumab s.c	Drug: Placebo; Placebo 150 or 300 mg s.c at randomization, Weeks 1, 2, 3, 4, and 8. PASI responders at week 12 continued to receive placebo till Week 48. PASI non-responders at Week 12 received Secukinumab 300mg at Weeks 12, 13, 14, 15, 16 and every 4 weeks till Week 48

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Psoriasis Area and Severity Index (PASI) 75 (Multiple Imputation)	Psoriasis Area and Severity Index (PASI) was assessed/calculated as per usual standard. result given in terms of count of participants with response in 100 imputations. 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).	Week 12
Investigator's Global Assessment (IGA) Mod 2011 0/1 (Multiple Imputation)	Investigator assessed disease using a validated scale (IGA mod 2011) and rate the disease from a score of 0 (clear skin) to 4 (severe disease). result given in terms of count of participants with response in 100 imputations. The Investigator's Global Assessment (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. Treatment success was defined as achievement of IGA mod 2001 score of 0 or 1.	Week 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Psoriasis Area and Severity Index (PASI) 90 (Multiple Imputation)	Psoriasis Area and Severity Index (PASI) was assessed/calculated as per usual standard. result given in terms of count of participants with response in 100 imputations. 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).	Week 12
Efficacy of Secukinumab in Maintaining PASI 75 Response at Week 52 in Subjects Who Were PASI 75 Responders at Week 12 (Multiple Imputation)	Psoriasis Area and Severity Index (PASI) was assessed/calculated as per usual standard. result given in terms of count of participants with response in 100 imputations. 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).	Week 52
Efficacy of Secukinumab in Maintaining IGA Mod 2011 0 or 1 Response at Week 52 in Subjects Who Were IGA Mod 2011 0 or 1 Responders at Week 12 (Multiple Imputation)	Investigator assessed disease using a validated scale (IGA mod 2011) and rate the disease from a score of 0 (clear skin) to 4 (severe disease). result given in terms of count of participants with response in 100 imputations. The Investigator's Global Assessment (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. Treatment success was defined as achievement of IGA mod 2001 score of 0 or 1.	Week 52
PASI 50/75/90/100 and IGA Mod 2011 0 or 1 Response Over Time (Multiple Imputation)	Number (%) of subjects with PASI 50, PASI 75, PASI 90, PASI 100 and IGA mod 2011 0 or 1 response	week 1, week 12, week 24, week 52
American Collage of Rheumatology (ACR) Response 20/50/70	Percentage of patients who achieved ACR 20/50/70 at Week 12 and up to Week 52. The subset of patients who had active PsA at baseline included 7 patients in the secukinumab 150 mg group, 17 patients in the secukinumab 300 mg group and 4 patients in the placebo group. ACR 20, 50 or 70 responses correspond, respectively, to at least 20%, 50% or 70% improvement in comparison with baseline in the number of tender and swollen joint counts, in addition to similar improvements in at least three of five other measure of disability or disease activity	week 12, week 24, week 52
Time to PASI 75 Response up to Week 12	Psoriasis Area and Severity Index (PASI) was assessed/calculated as per usual standard. result given in terms of count of participants with response in 100 imputations. 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).	week 12

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Publications and helpful links

General Publications

• Cai L, Zhang JZ, Yao X, Gu J, Liu QZ, Zheng M, Zhang SF, Xu JH, Li CX, Cheng H, Guo Q, Pan WL, Li SQ, Li RY, Guo ZP, Song ZQ, Li SS, Dong XQ, Wang L, Fu R, Regnault P, Charef P, Mazur R, Patekar M. Secukinumab demonstrates high efficacy and a favorable safety profile over 52 weeks in Chinese patients with moderate to severe plaque psoriasis. Chin Med J (Engl). 2020 Nov 20;133(22):2665-2673. doi: 10.1097/CM9.0000000000001163.

Study record dates

Study Major Dates

• Study Start (Actual): February 28, 2017
• Primary Completion (Actual): December 21, 2017
• Study Completion (Actual): November 20, 2018

Study Registration Dates

• First Submitted: February 22, 2017
• First Submitted That Met QC Criteria: February 22, 2017
• First Posted (Actual): February 28, 2017

Study Record Updates

• Last Update Posted (Actual): December 30, 2019
• Last Update Submitted That Met QC Criteria: December 9, 2019
• Last Verified: December 1, 2019

More Information

Terms related to this study

• Keywords: psoriasis; Plaque psoriasis; skin disease; Secukinumab; itching; psoriasis vulgaris; immune-mediated systemic disease; skin lesions; scaly patches; papules; Skin condition
• Additional Relevant MeSH Terms: Skin Diseases; Skin Diseases, Papulosquamous; Psoriasis; Physiological Effects of Drugs; Immunologic Factors; Antibodies, Monoclonal
• Other Study ID Numbers: CAIN457A2318

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