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

• ClinicalTrials.gov Identifier: NCT03066609
• Recruitment Status: Completed
• First Posted: February 28, 2017
• Results First Posted: December 30, 2019
• Last Update Posted: December 30, 2019
• Sponsor: Novartis Pharmaceuticals
• Information provided by (Responsible Party): Novartis ( Novartis Pharmaceuticals )

Study Description

Brief Summary:

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

Condition or disease	Intervention/treatment	Phase
Plaque Psoriasis	Drug: Secukinumab 150 mg s.c.; Drug: Secukinumab 300 mg s.c.; Drug: Placebo	Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 543 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: 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
• Actual Study Start Date: February 28, 2017
• Actual Primary Completion Date: December 21, 2017
• Actual Study Completion Date: November 20, 2018

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. Psoriasis Area and Severity Index (PASI) 75 (Multiple Imputation) [ Time Frame: 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).
2. Investigator's Global Assessment (IGA) Mod 2011 0/1 (Multiple Imputation) [ Time Frame: Week 12 ]
   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.

Secondary Outcome Measures :

1. Psoriasis Area and Severity Index (PASI) 90 (Multiple Imputation) [ Time Frame: 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).
2. Efficacy of Secukinumab in Maintaining PASI 75 Response at Week 52 in Subjects Who Were PASI 75 Responders at Week 12 (Multiple Imputation) [ Time Frame: Week 52 ]
   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).
3. 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) [ Time Frame: Week 52 ]
   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.
4. PASI 50/75/90/100 and IGA Mod 2011 0 or 1 Response Over Time (Multiple Imputation) [ Time Frame: week 1, week 12, week 24, week 52 ]
   Number (%) of subjects with PASI 50, PASI 75, PASI 90, PASI 100 and IGA mod 2011 0 or 1 response
5. American Collage of Rheumatology (ACR) Response 20/50/70 [ Time Frame: week 12, week 24, week 52 ]
   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
6. Time to PASI 75 Response up to Week 12 [ Time Frame: 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).

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:

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.

Contacts and Locations

Locations

China, Beijing

Novartis Investigative Site

Beijing, Beijing, China, 100039

Novartis Investigative Site

Xicheng Direct, Beijing, China, 100044

China, Hubei

Novartis Investigative Site

Wuhan, Hubei, China, 430030

China, Jilin

Novartis Investigative Site

Chang Chun, Jilin, China, 130021

China, Liaoning

Novartis Investigative Site

Dalian, Liaoning, China, 116011

Novartis Investigative Site

Shenyang, Liaoning, China, 110000

China, Sichuan

Novartis Investigative Site

Chengdu, Sichuan, China, 610041

China, Zhejiang

Novartis Investigative Site

Hangzhou, Zhejiang, China, 310009

Novartis Investigative Site

Hangzhou, Zhejiang, China, 310014

Novartis Investigative Site

Hangzhou, Zhejiang, China, 310016

China

Novartis Investigative Site

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, 200040

Novartis Investigative Site

Shanghai, China, 200433

Novartis Investigative Site

Tianjin, China, 300052

Hungary

Novartis Investigative Site

Kecskemet, Bacs Kiskun, Hungary, 6000

Novartis Investigative Site

Kaposvar, Hungary, 7400

Novartis Investigative Site

Oroshaza, Hungary, 5900

Malaysia

Novartis Investigative Site

Batu Caves, Malaysia, 68100

Novartis Investigative Site

Penang, Malaysia, 10990

Philippines

Novartis Investigative Site

Makati City, Philippines, 1220

Novartis Investigative Site

Quezon City, Philippines, 1102

Thailand

Novartis Investigative Site

Bangkoknoi, Bangkok, Thailand, 10700

Novartis Investigative Site

Bangkok, Thailand, 10330

Novartis Investigative Site

Bangkok, Thailand, 10400

Turkey

Novartis Investigative Site

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

Sponsors and Collaborators

Novartis Pharmaceuticals

  Study Documents (Full-Text)

Documents provided by Novartis ( Novartis Pharmaceuticals ):

Study Protocol  [PDF] June 9, 2017

Statistical Analysis Plan  [PDF] September 11, 2019

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: Novartis Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT03066609
• Other Study ID Numbers: CAIN457A2318
• First Posted: February 28, 2017
• Results First Posted: December 30, 2019
• Last Update Posted: December 30, 2019
• Last Verified: December 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

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Novartis ( Novartis Pharmaceuticals ):

Plaque psoriasis; Secukinumab; Skin condition; skin disease; itching; psoriasis vulgaris; immune-mediated systemic disease; skin lesions; scaly patches; papules; psoriasis

Additional relevant MeSH terms:

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