Study to Assess the Long-term Safety, Tolerability, Efficacy of Secukinumab in Pediatric Patients of Age 6 to <18 Years, With Moderate to Severe Plaque Psoriasis

A Randomized, Open-label, Multicenter Trial to Assess the Efficacy of Subcutaneous Secukinumab after12 Weeks of Treatment, and to Assess the Long-term Safety, Tolerability, Efficacy in Subjects From 6 to <18 Years of Age With Moderate to Severe Chronic Plaque Psoriasis

This was an open-label, parallel-group, two-arm, multicenter study in pediatric subjects aged 6 years to less than 18 years, at randomization, with moderate to severe chronic plaque psoriasis. 84 subjects (most with moderate severity) were enrolled. Subjects were stratified by weight and disease severity.

Study Overview

• Status: Completed
• Conditions: Moderate to Severe Chronic Plaque-type Psoriasis
• Intervention / Treatment: Drug: secukinumab low dose; Drug: secukinumab high dose

Detailed Description

This was an open-label, parallel group, two-arm, multi-center, trial in pediatric subjects aged 6 years to less than 18 years, at randomization, with moderate to severe chronic, plaque psoriasis. The study consists of 3 periods: screening (up to 4 weeks), treatment (Week 208) and post-treatment follow-up (Week 224).

Approximately 80 subjects (at least 60 subjects with moderate psoriasis) were planned to be enrolled in about 40 centers worldwide and targeted to have at least 5 subjects in the < 25kg body weight, and at least 10 subjects in each of the other two weight groups (25-< 50 kg and ≥ 50 kg). Adolescents (12-< 18 years) and children (6-< 12 years) were included from the beginning of this study, since the DMC had approved already the enrollment of children (6-< 12 years) in the study CAIN457A2310 (NCT02471144). Subjects received the appropriate dose based on their body weight category.

For the statistical analysis for outcome measures 1 and 2, there was no 'within study' control arm. A historical placebo control was obtained using data from qualifying trials and used as the comparator for the primary and key secondary endpoint analysis. This was in line with the guidance from and discussions with Health Authorities including FDA and EMA (PDCO), which suggested reducing placebo exposure as well as overall clinical trial burden for the pediatric population and accepted an extrapolation approach (EMA 2012). Historical placebo data included in this study were based on clinical appropriateness and alignment of definitions (endpoints, clinical disease population and time point of assessment). Integrated in the analysis were placebo data from Novartis-reported secukinumab adult placebo-controlled studies (CAIN457A2302 (NCT01544595 and NCT01365455), CAIN457A2303 (NCT01544595 and NCT01358578), CAIN457A2308 (NCT01555125) and CAIN457A2309 (NCT01636687)) and pediatric placebo-controlled study CAIN457A2310. In addition, pediatric placebo-controlled study data from the literature on other biologics (e.g. etanercept, ustekinumab) were utilized (Paller et al 2008, Landells et al 2015).

If the subject moved into a higher or lower weight group at two consecutive visits with weight measurements during the maintenance (from Week 12 onwards as assessed at 4 weekly visits or during extension treatment period (as assessed at scheduled site visits), then the subject was dosed according to the new (higher or lower) weight group respectively.

• Study Type: Interventional
• Enrollment (Actual): 84
• Phase: Phase 3

Contacts and Locations

Study Locations

• Belgium
  • Bruxelles, Belgium, 1200
    • Novartis Investigative Site
  • Liege, Belgium, 4000
    • Novartis Investigative Site
• Czechia
  • CZE
    • Hradec Kralove, CZE, Czechia, 500 05
      • Novartis Investigative Site
  • Prague 1
    • Prague, Prague 1, Czechia, 11000
      • Novartis Investigative Site
• Estonia
  • Tartu, Estonia, 50406
    • Novartis Investigative Site
• Germany
  • Dresden, Germany, 01307
    • Novartis Investigative Site
  • Muenster, Germany, 48149
    • Novartis Investigative Site
• Peru
  • Lima, Peru, 1
    • Novartis Investigative Site
• Poland
  • Rzeszow, Poland, 35 055
    • Novartis Investigative Site
  • Wroclaw, Poland, 50-566
    • Novartis Investigative Site
  • Mazowian
    • Warszawa, Mazowian, Poland, 02 495
      • Novartis Investigative Site
• Russian Federation
  • Kazan, Russian Federation, 420012
    • Novartis Investigative Site
  • Krasnodar, Russian Federation, 350020
    • Novartis Investigative Site
  • Moscow, Russian Federation, 119296
    • Novartis Investigative Site
  • Saint Petersburg, Russian Federation, 191123
    • Novartis Investigative Site
• Spain
  • Madrid, Spain, 28041
    • Novartis Investigative Site
  • Valencia, Spain, 46026
    • Novartis Investigative Site
  • Barcelona
    • Esplugues De Llobregat, Barcelona, Spain, 08950
      • Novartis Investigative Site
    • Sabadell, Barcelona, Spain, 08208
      • Novartis Investigative Site
• United States
  • California
    • Fountain Valley, California, United States, 92708
      • First OC Dermatology
  • Florida
    • Jacksonville, Florida, United States, 32256
      • Private Practice
  • New Hampshire
    • Lebanon, New Hampshire, United States, 03756
      • Novartis Investigative Site
  • Texas
    • San Antonio, Texas, United States, 78218
      • Texas Derm and Laser Specialists .

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 years to 17 years (Child)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Written informed assent and parental permission (age as per local law) obtained at screening before any assessment is performed.
2. Must be 6 to less than 18 years of age at the time of randomization
3. Moderate to Severe plaque psoriasis, defined as a PASI score ≥ 12, and IGA mod 2011 score of ≥ 3, and BSA involvement of ≥10%, at randomization.
4. Subject being regarded by the investigator to be a candidate for systemic therapy.

Exclusion Criteria:

1. Forms of psoriasis other than chronic plaque-type active at randomization
2. Drug-induced psoriasis
3. Ongoing use of prohibited treatments
4. Female subjects of childbearing potential defined as all women physiologically capable of becoming pregnant, unless they are using effective methods of contraception during dosing and for 16 weeks after stopping study treatment
5. Pregnant or nursing (lactating) females
6. Subjects with total WBC count <2,500/μL, or platelets <100,000/μL or neutrophils <1,500/μL or hemoglobin <8.5 g/dL at screening
7. Previous exposure to secukinumab or any other biologic drug directly targeting IL-17 or the IL-17 receptor

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: secukinumab low dose	Drug: secukinumab low dose; dose depends on the weight group; Other Names: AIN457
Experimental: secukinumab high dose	Drug: secukinumab high dose; dose depends on the weight group; Other Names: AIN457

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number and Percentage of Participants With PASI 75 Response	Psoriasis Area and Severity Index (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, trunk, upper limbs and lower limbs); 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,Thickening (plaque elevation, induration) & Scaling(desquamation). Scale 0 (none) to 4 (maximum). Final PASI = sum of severity parameters for each area* area score weight of section(head: 0.1, upper limbs: 0.2 body: 0.3 lower limbs: 0.4). Psoriasis Area and Severity Index (PASI) will be assessed/calculated as per standard procedure. PASI 75 represents the percentage (or number)of patients who have achieved a 75% or more reduction in their PASI score from baseline. PASI 100 indicates patients who have achieved a complete resolution of all disease.	Week 12
Number and Percentage of Participants With IGA Mod 2011 0 or 1 Response	Investigator will assess the disease using the validated Investigator Global Assessment (IGA) mod 2011 and rate the disease from a score of 0 (clear skin) to 4 (severe disease)	Week 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number and Percentage of Participants With PASI 90 Response	Psoriasis Area and Severity Index (PASI) was assessed/calculated as per the standard procedure. PASI 90 represents the percentage (or number) of patients who have achieved a 90% or more reduction in their PASI score from baseline. PASI 100 indicates patients who have achieved a complete resolution of all disease.	Week 12
Secukinumab Concentration in Serum	Mean (Standard Deviation) Secukinumab concentration levels in serum over time.	Baleine, Weeks 4, 12, 13, 14, 15, 16, 24, 52, 104, 156, 208
Summary Table of Adverse Events	An adverse event (AE) is any untoward medical occurrence (e.g. any unfavorable and unintended sign [including abnormal laboratory findings], symptom or disease) in a clinical investigation participant after providing written informed consent for participation in the study. Treatment emergent adverse events in this study are events that started after the first dose of study treatment and until 84 days after the last study treatment, or events present prior to the first dose of treatment which increased in severity based on preferred term within 84 days after the last study treatment.	Adverse events are reported from the first dose of study-drug until the end of the treatment period (at Week 208) plus 16 weeks additional follow up reporting, for a maximum timeframe of approximately 224 weeks.

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals
• Investigators: Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Publications and helpful links

General Publications

• Magnolo N, Kingo K, Laquer V, Browning J, Reich A, Szepietowski JC, Keefe D, Papanastasiou P, Bao W, Forrer P, Patekar M. Efficacy of Secukinumab Across Subgroups and Overall Safety in Pediatric Patients with Moderate to Severe Plaque Psoriasis: Week 52 Results from a Phase III Randomized Study. Paediatr Drugs. 2022 Jul;24(4):377-387. doi: 10.1007/s40272-022-00507-0. Epub 2022 Jun 13.
• Magnolo N, Kingo K, Laquer V, Browning J, Reich A, Szepietowski JC, Keefe D, Mazur R, Ghelani P, Forrer P, Wraith L, Patekar M. A phase 3 open-label, randomized multicenter study to evaluate efficacy and safety of secukinumab in pediatric patients with moderate to severe plaque psoriasis: 24-week results. J Am Acad Dermatol. 2022 Jan;86(1):122-130. doi: 10.1016/j.jaad.2021.08.066. Epub 2021 Sep 30.

Study record dates

Study Major Dates

• Study Start (Actual): August 29, 2018
• Primary Completion (Actual): September 19, 2019
• Study Completion (Actual): September 12, 2023

Study Registration Dates

• First Submitted: August 23, 2018
• First Submitted That Met QC Criteria: September 10, 2018
• First Posted (Actual): September 12, 2018

Study Record Updates

• Last Update Posted (Actual): March 20, 2024
• Last Update Submitted That Met QC Criteria: February 23, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: plaques; pediatric; skin disease; plaque psoriasis; itching; psoriasis vulgaris; immune-mediated systemic disease; skin lesions; scaly patches; papules; Skin condition; secukinumab; AIN457A; itching condition; relapsing/remitting psoriasis; red skin lesions
• Additional Relevant MeSH Terms: Skin Diseases; Skin Diseases, Papulosquamous; Psoriasis; Physiological Effects of Drugs; Immunologic Factors; Antibodies, Monoclonal
• Other Study ID Numbers: CAIN457A2311; 2017-004515-39 (EudraCT Number)

Plan for Individual participant data (IPD)

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

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