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 )

Tracking Information

• First Submitted Date: February 22, 2017
• First Posted Date: February 28, 2017
• Results First Submitted Date: November 14, 2019
• Results First Posted Date: December 30, 2019
• Last Update Posted Date: December 30, 2019
• Actual Study Start Date: February 28, 2017
• Actual Primary Completion Date: December 21, 2017 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: December 9, 2019)

• 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).
• 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.

Original Primary Outcome Measures (submitted: February 22, 2017)

• Psoriasis Area and Severity Index (PASI) 75 [ Time Frame: Week 12 ]
  Psoriasis Area and Severity Index (PASI) will be assessed/calculated as per usual standard.
• Investigator's Global Assessment (IGA) mod 2011 0/1 [ Time Frame: Week 12 ]
  Investigator will assess disease using a validated scale (IGA mod 2011) and rate the disease from a score of 0 (clear skin) to 4 (severe disease).

Current Secondary Outcome Measures (submitted: December 9, 2019)

• 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).
• 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).
• 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.
• 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
• 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
• 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).

Original Secondary Outcome Measures (submitted: February 22, 2017)

• Psoriasis Area and Severity Index (PASI) [ Time Frame: Baseline to Week 52 ]
  Psoriasis Area and Severity Index (PASI) will be assessed/calculated as per usual standard
• Investigator's Global Assessment (IGA) mod 2011 0/1 [ Time Frame: Baseline to Week 52 ]
  Investigator will assess disease using a validated scale (IGA mod 2011) and rate the disease from a score of 0 (clear skin) to 4 (severe disease).
• American Collage of Rheumatology (ACR) Response 20/50/70 [ Time Frame: Baseline to Week 52 ]
  Percentage of patients who achieve ACR 20/50/70 at Week 12 and up to Week 52

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Study of Efficacy and Safety of Secukinumab in Subjects With Moderate to Severe Chronic Plaque-type Psoriasis
• 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
• Brief Summary: The purpose of this study was to determine if secukinumab is effective and safe in the treatment of plaque type psoriasis
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Plaque Psoriasis

Intervention

• Drug: Secukinumab 150 mg s.c.
  150 mg s.c. at randomization, Weeks 1, 2, 3, 4 and every 4 weeks till Week 48
• Drug: Secukinumab 300 mg s.c.
  300 mg s.c. at randomization, Weeks 1, 2, 3, 4 and every 4 weeks till Week 48
• 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

Study Arms

• Experimental: Secukinumab 150mg
  Secukinumab 150mg s.c.
  Intervention: Drug: Secukinumab 150 mg s.c.
• Experimental: Secukinumab 300mg
  Secukinumab 300mg s.c.
  Intervention: Drug: Secukinumab 300 mg s.c.
• Placebo Comparator: Placebo
  Placebo to secukinumab s.c
  Intervention: Drug: Placebo

• 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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: December 4, 2018): 543
• Original Estimated Enrollment (submitted: February 22, 2017): 536
• Actual Study Completion Date: November 20, 2018
• Actual Primary Completion Date: December 21, 2017 (Final data collection date for primary outcome measure)

Eligibility 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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: China, Hungary, Malaysia, Philippines, Thailand, Turkey

Administrative Information

• NCT Number: NCT03066609
• Other Study ID Numbers: CAIN457A2318
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

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

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

• Responsible Party: Novartis ( Novartis Pharmaceuticals )
• Study Sponsor: Novartis Pharmaceuticals
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Novartis
• Verification Date: December 2019