Clinical trial NCT02471144: Pediatric Study in Children and Adolescents With Severe Plaque Psoriasis
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Chronic Severe Plaque-type Psoriasis
Keywords: pediatric
chronic severe plaque psoriasis
secukinumab
etanercept
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2015-06-15
Enrollment: 162
Sex: ALL
Minimum age (years): 6
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.
* Other protocol-defined inclusion/exclusion criteria may apply.

Primary outcomes:
measure: Number and Percentage of Participants Achieving a 75% Improvement From Baseline in PASI Score at Week 12
timeFrame: 12 weeks
measure: Number and Percentage of Participants Who Showed Investigator's Global Assessment (IGA) Mod 2011 Response of 0 or 1 at Week 12
timeFrame: 12 Weeks
Secondary outcomes:
measure: Number and Percentage of Participants Achieving a 90% Improvement From Baseline in PASI Score at Week 12
timeFrame: 12 weeks
measure: Number and Percentage of Participants Achieving a 50%, 100% Improvement From Baseline in PASI Score at Week 12
timeFrame: 12 weeks
measure: 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)
timeFrame: Weeks 4, 8
measure: 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)
timeFrame: Weeks 16, 20, 24, 36, 48 and 52
measure: Change From Baseline in Psoriasis Area & Severity Index (PASI) Score at Week 12
timeFrame: Week 12
measure: Change From Baseline in Psoriasis Area & Severity Index (PASI) Scores at Week 52
timeFrame: Week 52
measure: Percentage of Participants in IGA Mod 2011 Score Categories at Week 12
timeFrame: Week 12
measure: Percentage of Participants in IGA Mod 2011 Score Categories at Week 52
timeFrame: Week 52
measure: Percentage Change From Baseline in Children's Dermatology Life Quality Index (cDLQI) Score Up to Week 12 (Induction)
timeFrame: Weeks 4, 8, 12
measure: Percentage Change From Baseline in Children's Dermatology Life Quality Index (cDLQI) Score Up to Week 52 (Maintenance)
timeFrame: Weeks 24, 36, 52
measure: Number and Percentage of Participants Achieving a Children's DLQI Score of 0 or 1 Over Time up to Week 12 (Induction)
timeFrame: Weeks 4, 8, 12
measure: Number and Percentage of Participants Achieving a Children's DLQI Score of 0 or 1 Over Time up to Week 52 (Maintenance)
timeFrame: Weeks 24, 36, 52
measure: Number and Percentage of Participants With Clinically Important Reduction in Disability as Evaluated by CHAQ Questionnaire Over Time at Week 12
timeFrame: Week 12
measure: Number and Percentage of Participants With Clinically Important Reduction in Disability as Evaluated by CHAQ Questionnaire Over Time at Week 52
timeFrame: Week 52
Other outcomes:
Locations:
city: San Antonio
country: United States
facility: Novartis Investigative Site
state: Texas
city: Bruxelles
country: Belgium
facility: Novartis Investigative Site
city: Gent
country: Belgium
facility: Novartis Investigative Site
city: Liege
country: Belgium
facility: Novartis Investigative Site
city: Medellin
country: Colombia
facility: Novartis Investigative Site
state: Antioquia
city: Bogota
country: Colombia
facility: Novartis Investigative Site
city: Alexandria
country: Egypt
facility: Novartis Investigative Site
city: Cairo
country: Egypt
facility: Novartis Investigative Site
city: Tartu
country: Estonia
facility: Novartis Investigative Site
city: Amiens Cedex 1
country: France
facility: Novartis Investigative Site
city: Nice
country: France
facility: Novartis Investigative Site
city: Paris 15
country: France
facility: Novartis Investigative Site
city: Bad Bentheim
country: Germany
facility: Novartis Investigative Site
city: Bochum
country: Germany
facility: Novartis Investigative Site
city: Dresden
country: Germany
facility: Novartis Investigative Site
city: Erlangen
country: Germany
facility: Novartis Investigative Site
city: Mainz
country: Germany
facility: Novartis Investigative Site
city: Muenchen
country: Germany
facility: Novartis Investigative Site
city: Muenster
country: Germany
facility: Novartis Investigative Site
city: Guatemala city
country: Guatemala
facility: Novartis Investigative Site
city: Guatemala City
country: Guatemala
facility: Novartis Investigative Site
city: Budapest
country: Hungary
facility: Novartis Investigative Site
city: Budapest
country: Hungary
facility: Novartis Investigative Site
city: Debrecen
country: Hungary
facility: Novartis Investigative Site
city: Afula
country: Israel
facility: Novartis Investigative Site
city: Be'er Sheva
country: Israel
facility: Novartis Investigative Site
city: Ramat Gan
country: Israel
facility: Novartis Investigative Site
city: Parma
country: Italy
facility: Novartis Investigative Site
state: PR
city: Roma
country: Italy
facility: Novartis Investigative Site
state: RM
city: Nagoya-city
country: Japan
facility: Novartis Investigative Site
state: Aichi
city: Riga
country: Latvia
facility: Novartis Investigative Site
city: Riga
country: Latvia
facility: Novartis Investigative Site
city: Lodz
country: Poland
facility: Novartis Investigative Site
city: Lublin
country: Poland
facility: Novartis Investigative Site
city: Warszawa
country: Poland
facility: Novartis Investigative Site
city: Cluj Napoca
country: Romania
facility: Novartis Investigative Site
state: Cluj
city: Kazan
country: Russian Federation
facility: Novartis Investigative Site
city: Krasnodar
country: Russian Federation
facility: Novartis Investigative Site
city: Moscow
country: Russian Federation
facility: Novartis Investigative Site
city: Saint Petersburg
country: Russian Federation
facility: Novartis Investigative Site
city: Yekaterinburg
country: Russian Federation
facility: Novartis Investigative Site
city: Esplugues De Llobregat
country: Spain
facility: Novartis Investigative Site
state: Barcelona
city: Barcelona
country: Spain
facility: Novartis Investigative Site
city: Madrid
country: Spain
facility: Novartis Investigative Site
city: Zuerich
country: Switzerland
facility: Novartis Investigative Site
city: Scunthorpe
country: United Kingdom
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References: