Pediatric Study in Children and Adolescents With Severe Plaque Psoriasis

NCT ID: NCT02471144

Last Updated: 2023-10-11

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 162 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-09-29
• Study Completion Date: 2023-03-30

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).

The screening period of up to 4 weeks was used to assess eligibility of the patients and to taper patients off prohibited medications.

The Induction period is defined as randomization through Week 12. In this period, the study was both active and placebo-controlled and at its completion, the primary endpoint was assessed (Week 12).

The Maintenance period is defined as Week 12 (from dosing) through Week 52. During this period, the study was active-controlled, and the objectives focused on the maintenance of the response observed at Week 12.

Patients who received secukinumab or etanercept during induction continued in maintenance with the same treatment. Patients who were on placebo during induction and at Week 12 were PASI 75 non-responders were switched to either secukinumab low dose or secukinumab high dose treatment group in the Maintenance period according to their baseline randomization.

At the end of the Maintenance period, all patients on secukinumab entered the Extension treatment period and continued to receive the same dose of secukinumab. The Extension treatment period was defined as Week 52 (from dosing) until Week 236. In this period, all patients were treated with secukinumab, and the purpose was the collection of long-term safety and efficacy data.

Patients who participated in the Maintenance period but prematurely discontinued the study were not able to enter the Extension treatment period. Patients receiving etanercept were not eligible to enter the Extension treatment period. Instead, at Week 52, they completed an EOM visit and then entered the post-treatment Follow-up period.

Conditions

Chronic Severe Plaque-type Psoriasis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Secukinumab low dose

Secukinumab

Group Type: EXPERIMENTAL

Experimental : Secukinumab low dose

Intervention Type: BIOLOGICAL

Depending on weight group subject will receive per dose a) 75 mg if weighing less than 50 kg b) 150 mg if weighing 50 kg or more. Secukinumab injections (one or two per dose, depending on the weight group) will be administered subcutaneously at Randomization, Weeks 1, 2, 3, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, and 48, and Placebo secukinumab at Weeks 13, 14 and 15 during the blinded phase of the study; thereafter at Week 52 and every 4 weeks during the extension treatment period until Week 232.

Secukinumab high dose

Secukinumab

Group Type: EXPERIMENTAL

Experimental: Secukinumab high dose

Intervention Type: BIOLOGICAL

Depending on weight group subject will receive per dose a) 75 mg if weighing less than 25 kg b) 150 mg if weighing between 25 and less than 50 kg c) 300 mg if weighing more than 50 kg. Secukinumab injections (one or two per dose, depending on the weight group) will be administered subcutaneously at Randomization, Weeks 1, 2, 3, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, and 48, and Placebo secukinumab at Weeks 13, 14 and 15 during the blinded phase of the study; thereafter at Week 52 and every 4 weeks during the extension treatment period until Week 232.

Placebo

Placebo

Group Type: PLACEBO_COMPARATOR

Placebo Comparator: Secukinumab Placebo

Intervention Type: BIOLOGICAL

Placebo secukinumab (one or two subcutaneous injections per dose, depending on weight group) at Randomization and Weeks 1, 2, 3 4 and 8. At Week 12, subjects in the placebo group based on their PASI 75 response status at Week 12 will proceed as follows: • PASI 75 responders will discontinue study treatment at Week 12 and enter the treatment-free follow-up period • PASI 75 non-responders will receive high dose or low dose secukinumab, according to the pre-assignment at the Randomization visit. They will receive their treatment based on the weight category(\<25 kg, 25- \<50kg, ≥50 kg), on Weeks 12, 13, 14, 15, and then every four weeks starting at Week 16 until Week 48 during the maintenance period; thereafter at week 52 and every 4 weeks during the extension treatment period until Week 232.

Etanercept Comparator

Etanercept

Group Type: ACTIVE_COMPARATOR

Active Comparator: Etanercept

Intervention Type: BIOLOGICAL

Etanercept 0.8 mg/kg of subject weight and up to a maximum of 50 mg per dose. Subcutaneous etanercept 0.8 mg/kg (one or two injections per dose) once per week, for 51 weeks administered at home (self-injected or by caregiver) or at the study site. At Wk 52 subjects in the etanercept group will move into the treatment-free follow up period and terminate the study.

Interventions

Experimental : Secukinumab low dose

Depending on weight group subject will receive per dose a) 75 mg if weighing less than 50 kg b) 150 mg if weighing 50 kg or more. Secukinumab injections (one or two per dose, depending on the weight group) will be administered subcutaneously at Randomization, Weeks 1, 2, 3, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, and 48, and Placebo secukinumab at Weeks 13, 14 and 15 during the blinded phase of the study; thereafter at Week 52 and every 4 weeks during the extension treatment period until Week 232.

Intervention Type: BIOLOGICAL

Experimental: Secukinumab high dose

Depending on weight group subject will receive per dose a) 75 mg if weighing less than 25 kg b) 150 mg if weighing between 25 and less than 50 kg c) 300 mg if weighing more than 50 kg. Secukinumab injections (one or two per dose, depending on the weight group) will be administered subcutaneously at Randomization, Weeks 1, 2, 3, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, and 48, and Placebo secukinumab at Weeks 13, 14 and 15 during the blinded phase of the study; thereafter at Week 52 and every 4 weeks during the extension treatment period until Week 232.

Intervention Type: BIOLOGICAL

Placebo Comparator: Secukinumab Placebo

Placebo secukinumab (one or two subcutaneous injections per dose, depending on weight group) at Randomization and Weeks 1, 2, 3 4 and 8. At Week 12, subjects in the placebo group based on their PASI 75 response status at Week 12 will proceed as follows: • PASI 75 responders will discontinue study treatment at Week 12 and enter the treatment-free follow-up period • PASI 75 non-responders will receive high dose or low dose secukinumab, according to the pre-assignment at the Randomization visit. They will receive their treatment based on the weight category(\<25 kg, 25- \<50kg, ≥50 kg), on Weeks 12, 13, 14, 15, and then every four weeks starting at Week 16 until Week 48 during the maintenance period; thereafter at week 52 and every 4 weeks during the extension treatment period until Week 232.

Intervention Type: BIOLOGICAL

Active Comparator: Etanercept

Etanercept 0.8 mg/kg of subject weight and up to a maximum of 50 mg per dose. Subcutaneous etanercept 0.8 mg/kg (one or two injections per dose) once per week, for 51 weeks administered at home (self-injected or by caregiver) or at the study site. At Wk 52 subjects in the etanercept group will move into the treatment-free follow up period and terminate the study.

Intervention Type: BIOLOGICAL

Other Intervention Names

AIN457 low dose; AIN457 high dose; AIN457 placebo; Etanercept

Eligibility Criteria

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:

1. inadequate control of symptoms with topical treatment, or

2. 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.

• Minimum Eligible Age: 6 Years
• Maximum Eligible Age: 17 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Novartis Pharmaceuticals

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Novartis Pharmaceuticals

Role: STUDY_DIRECTOR

Novartis Pharmaceuticals

Locations

Novartis Investigative Site

San Antonio, Texas, United States

Novartis Investigative Site

Brussels, , Belgium

Novartis Investigative Site

Ghent, , Belgium

Novartis Investigative Site

Liège, , Belgium

Novartis Investigative Site

Medellín, Antioquia, Colombia

Novartis Investigative Site

Bogotá, , Colombia

Novartis Investigative Site

Alexandria, , Egypt

Novartis Investigative Site

Cairo, , Egypt

Novartis Investigative Site

Tartu, , Estonia

Novartis Investigative Site

Amiens, , France

Novartis Investigative Site

Nice, , France

Novartis Investigative Site

Paris, , France

Novartis Investigative Site

Bad Bentheim, , Germany

Novartis Investigative Site

Bochum, , Germany

Novartis Investigative Site

Dresden, , Germany

Novartis Investigative Site

Erlangen, , Germany

Novartis Investigative Site

Mainz, , Germany

Novartis Investigative Site

München, , Germany

Novartis Investigative Site

Münster, , Germany

Novartis Investigative Site

Guatemala City, , Guatemala

Novartis Investigative Site

Guatemala City, , Guatemala

Novartis Investigative Site

Budapest, , Hungary

Novartis Investigative Site

Budapest, , Hungary

Novartis Investigative Site

Debrecen, , Hungary

Novartis Investigative Site

Afula, , Israel

Novartis Investigative Site

Beersheba, , Israel

Novartis Investigative Site

Ramat Gan, , Israel

Novartis Investigative Site

Parma, PR, Italy

Novartis Investigative Site

Roma, RM, Italy

Novartis Investigative Site

Nagoya, Aichi-ken, Japan

Novartis Investigative Site

Riga, , Latvia

Novartis Investigative Site

Riga, , Latvia

Novartis Investigative Site

Lodz, , Poland

Novartis Investigative Site

Lublin, , Poland

Novartis Investigative Site

Warsaw, , Poland

Novartis Investigative Site

Cluj-Napoca, Cluj, Romania

Novartis Investigative Site

Kazan', , Russia

Novartis Investigative Site

Krasnodar, , Russia

Novartis Investigative Site

Moscow, , Russia

Novartis Investigative Site

Saint Petersburg, , Russia

Novartis Investigative Site

Yekaterinburg, , Russia

Novartis Investigative Site

Esplugues de Llobregat, Barcelona, Spain

Novartis Investigative Site

Barcelona, , Spain

Novartis Investigative Site

Madrid, , Spain

Novartis Investigative Site

Zurich, , Switzerland

Novartis Investigative Site

Scunthorpe, , United Kingdom

Countries

United States; Belgium; Colombia; Egypt; Estonia; France; Germany; Guatemala; Hungary; Israel; Italy; Japan; Latvia; Poland; Romania; Russia; Spain; Switzerland; United Kingdom

References

Sticherling M, Nikkels AF, Hamza AM, Kwong P, Szepietowski JC, El Sayed M, Ghislain PD, Khotko AA, Patekar M, Ortmann CE, Forrer P, Papanastasiou P, Keefe D. Secukinumab in Pediatric Patients with Plaque Psoriasis: Pooled Safety Analysis from Two Phase 3 Randomized Clinical Trials. Am J Clin Dermatol. 2023 Sep;24(5):821-835. doi: 10.1007/s40257-023-00782-8. Epub 2023 Jun 21.

Reference Type: DERIVED

PMID: 37341961 (View on PubMed)

Krasowska D, Gambichler T, Cortes C, Horev A, Compagno N, Dahale SS, Papanastasiou P, Keefe D. Long-term efficacy, safety and tolerability of secukinumab in children and adolescents with severe chronic plaque psoriasis: Two-year results from a Phase III double-blind, randomized controlled trial. J Eur Acad Dermatol Venereol. 2023 Mar 27. doi: 10.1111/jdv.19063. Online ahead of print.

Reference Type: DERIVED

PMID: 36971771 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2014-005663-32

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CAIN457A2310

Identifier Type: -

Identifier Source: org_study_id