A Randomized, Double-blind, Placebo- and Active Controlled Multicenter Trial to Demonstrate Efficacy of Subcutaneous Secukinumab Compared to Placebo and Etanercept (in a Single-blinded Arm) After Twelve Weeks of Treatment, and to Assess the Safety, Tolerability, and Long-term Efficacy in Subjects From 6 to Less Than 18 Years of Age With Severe Chronic Plaque Psoriasis
Trial Snapshot
- Phase
- Phase 3
- Status
- Completed
- Sponsor
- Novartis Pharmaceuticals
- Enrollment
- 162
- Locations
- 46
- Primary Endpoint
- Number and Percentage of Participants Achieving a 75% Improvement From Baseline in PASI Score at Week 12
Study Overview
Brief Summary
This was a multicenter, randomized, double-blind, placebo- and active-controlled (etanercept in single blinded arm) study in pediatric subjects aged 6 years to less than 18 years with severe chronic plaque psoriasis. Approximately 160 subjects aged 6 years to <18 years were enrolled, of which at least 30 were 6 years to <12 years old. Subjects were enrolled at approximately 70 study sites worldwide.
Detailed Description
The purpose of this study was to demonstrate superior efficacy of secukinumab versus placebo at Week 12, based on both PASI 75 and IGA mod 2011 0 or 1 response rates in children and adolescents aged 6 to less than 18 years with severe chronic plaque psoriasis who had inadequate control of symptoms with topical treatment, or failed to respond to or tolerate previous systemic treatment and/or UV therapy
The study assessed the long term safety and tolerability of secukinumab in this pediatric age group and described the efficacy and safety of secukinumab compared to etanercept. This study provided efficacy and safety data to support the extension of label of secukinumab to include children and adolescents (6 years to <18 years) with severe chronic plaque psoriasis
Two age subgroups were studied in a staggered approach within this clinical study: 12 to less than 18 years of age, and 6 to less than 12 years of age . Enrolment of children aged 6 to less than 12 years began after a favorable recommendation by an independent external Data Monitoring Committee (DMC) who reviewed data of approximately 80 adolescents. Adolescents continued to be recruited while the data from the first 80 subjects was being collected and analyzed
Subjects were randomized using a 1:1:1:1 ratio into one of the treatment arms: secukinumab low dose, secukinumab high dose, etanercept or placebo. Subjects randomized to secukinumab treatment arms (high dose and low dose) received dose based on the weight category (<25 kg, 25 to <50kg, ≥50 kg).
The study consisted of 5 periods: screening (up to 4 weeks), induction (of 12 weeks), maintenance (of 40 weeks), extension treatment epoch (open-label of 184 weeks) and post- treatment follow-up epoch (of 16 weeks).
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Double (Participant, Investigator)
Eligibility Criteria
- Ages
- 6 Years to 17 Years (Child)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Must be 6 to less than 18 years of age at the time of randomization
- •Plaque-type psoriasis history for at least 3 months.
- •Severe plaque-type psoriasis meeting all of the following three criteria:
- •PASI score of 20 or greater,
- •Investigator's Global Assessment (IGA) score of 4
- •Total body surface area (BSA) affected of 10% or greater.
- •Patient being regarded by the investigator to be a candidate for systemic therapy because of:
- •inadequate control of symptoms with topical treatment, or
- •failure to respond to or tolerate previous systemic treatment and/or UV therapy
Exclusion Criteria
- •Current forms of psoriasis other than chronic plaque-type psoriasis (for example, pustular, erythrodermic, guttate) at randomization.
- •Current drug-induced psoriasis.
- •Previous use of secukinumab or any drug that targets IL-17 or IL-17 receptor.
- •Underlying condition (including, but not limited to metabolic, hematologic, renal, hepatic, pulmonary, neurologic, endocrine, cardiac, infectious or gastrointestinal) which in the opinion of the investigator significantly immunocompromises the subject and/or places the subject at unacceptable risk for receiving an immunomodulatory therapy
- •History of an ongoing, chronic or recurrent infectious disease, or evidence of untreated tuberculosis.
- •History of lymphoproliferative disease or history of malignancy of any organ system within the past 5 years.
- •Pregnant or nursing (lactating) women.
- •Other protocol-defined inclusion/exclusion criteria may apply.
Arms & Interventions
Secukinumab high dose
Secukinumab
Intervention: Experimental: Secukinumab high dose (Biological)
Placebo
Placebo
Intervention: Placebo Comparator: Secukinumab Placebo (Biological)
Secukinumab low dose
Secukinumab
Intervention: Experimental : Secukinumab low dose (Biological)
Etanercept Comparator
Etanercept
Intervention: Active Comparator: Etanercept (Biological)
Outcomes
Primary Outcomes
Number and Percentage of Participants Achieving a 75% Improvement From Baseline in PASI Score at Week 12
Time Frame: 12 weeks
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 trunk: 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.
Number and Percentage of Participants Who Showed Investigator's Global Assessment (IGA) Mod 2011 Response of 0 or 1 at Week 12
Time Frame: 12 Weeks
IGA: The IGA mod 2011 scale has following different scores for the state of disease: 0: Clear, No signs of psoriasis. 1: Almost clear 2: Mild 3: Moderate 4 : Severe
Secondary Outcomes
- Change From Baseline in Psoriasis Area & Severity Index (PASI) Score at Week 12(Week 12)
- Number and Percentage of Participants With Clinically Important Reduction in Disability as Evaluated by CHAQ Questionnaire Over Time at Week 12(Week 12)
- Number and Percentage of Participants Achieving a 90% Improvement From Baseline in PASI Score at Week 12(12 weeks)
- Number and Percentage of Participants Achieving a 50%, 100% Improvement From Baseline in PASI Score at Week 12(12 weeks)
- Number and Percentage of Participants Achieving a 50%, 75%, 90% or 100% Improvement From Baseline in PASI Score and IGA Mod 2011 Score of 0 or 1 Up to Week 52 (Maintenance)(Weeks 16, 20, 24, 36, 48 and 52)
- Change From Baseline in Psoriasis Area & Severity Index (PASI) Scores at Week 52(Week 52)
- Percentage of Participants in IGA Mod 2011 Score Categories at Week 12(Week 12)
- Percentage of Participants in IGA Mod 2011 Score Categories at Week 52(Week 52)
- Percentage Change From Baseline in Children's Dermatology Life Quality Index (cDLQI) Score Up to Week 12 (Induction)(Weeks 4, 8, 12)
- Number and Percentage of Participants Achieving a Children's DLQI Score of 0 or 1 Over Time up to Week 52 (Maintenance)(Weeks 24, 36, 52)
- Number and Percentage of Participants With Clinically Important Reduction in Disability as Evaluated by CHAQ Questionnaire Over Time at Week 52(Week 52)
- Number and Percentage of Participants Achieving a 50%, 75%, 90% or 100% Improvement From Baseline in PASI Score and IGA Mod 2011 Score of 0 or 1 up to Week 12 (Induction)(Weeks 4, 8)
- Percentage Change From Baseline in Children's Dermatology Life Quality Index (cDLQI) Score Up to Week 52 (Maintenance)(Weeks 24, 36, 52)
- Number and Percentage of Participants Achieving a Children's DLQI Score of 0 or 1 Over Time up to Week 12 (Induction)(Weeks 4, 8, 12)