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

Moderate to Severe Chronic Plaque-type Psoriasis Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03668613
• Other study ID #: CAIN457A2311
• Secondary ID: 2017-004515-39
• Status: Completed
• Phase: Phase 3
• Start date: August 29, 2018
• Est. completion date: September 12, 2023

Study information

• Verified date: February 2024
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 84
• Est. completion date: September 12, 2023
• Est. primary completion date: September 19, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 6 Years to 17 Years

Eligibility

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

Related Conditions & MeSH terms

• Moderate to Severe Chronic Plaque-type Psoriasis
• Psoriasis

Intervention

Drug:
• secukinumab low dose
dose depends on the weight group
• secukinumab high dose
dose depends on the weight group

Locations

Country	Name	City	State
Belgium	Novartis Investigative Site	Bruxelles
Belgium	Novartis Investigative Site	Liege
Czechia	Novartis Investigative Site	Hradec Kralove	CZE
Czechia	Novartis Investigative Site	Prague	Prague 1
Estonia	Novartis Investigative Site	Tartu
Germany	Novartis Investigative Site	Dresden
Germany	Novartis Investigative Site	Muenster
Peru	Novartis Investigative Site	Lima
Poland	Novartis Investigative Site	Rzeszow
Poland	Novartis Investigative Site	Warszawa	Mazowian
Poland	Novartis Investigative Site	Wroclaw
Russian Federation	Novartis Investigative Site	Kazan
Russian Federation	Novartis Investigative Site	Krasnodar
Russian Federation	Novartis Investigative Site	Moscow
Russian Federation	Novartis Investigative Site	Saint Petersburg
Spain	Novartis Investigative Site	Esplugues De Llobregat	Barcelona
Spain	Novartis Investigative Site	Madrid
Spain	Novartis Investigative Site	Sabadell	Barcelona
Spain	Novartis Investigative Site	Valencia
United States	First OC Dermatology	Fountain Valley	California
United States	Private Practice	Jacksonville	Florida
United States	Novartis Investigative Site	Lebanon	New Hampshire
United States	Texas Derm and Laser Specialists .	San Antonio	Texas

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

United States,  Belgium,  Czechia,  Estonia,  Germany,  Peru,  Poland,  Russian Federation,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	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
Secondary	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
Secondary	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.