Clinical trial NCT03031782: Secukinumab Safety and Efficacy in Juvenile Psoriatic Arthritis (JPsA) and Enthesitis-related Arthritis (ERA)
Official title: A Three-part Randomized, Double-blind, Placebo-controlled Study to Investigate the Efficacy and Safety of Secukinumab Treatment in Juvenile Idiopathic Arthritis Subtypes of Psoriatic and Enthesitis-related Arthritis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Juvenile Psoriatic Arthritis
Enthesitis-related Arthritis
Keywords: JIA
JPsA
ERA
Secukinumab
ILAR
Arthritis
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2017-01-26
Enrollment: 86
Sex: ALL
Minimum age (years): 2
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This was a double-blind, placebo-controlled, event-driven randomized withdrawal study to investigate the efficacy and safety of secukinumab treatment in the Juvenile Idiopathic Arthritis (JIA) categories of Juvenile Psoriatic Arthritis (JPsA) and Enthesitis-related Arthritis (ERA). The study was divided into 3 parts (plus a post-treatment follow-up period) consisting of open-label, single-arm active treatment in Treatment Periods 1 and 3 and a randomized, double-blind, placebo controlled, event-driven withdrawal design in Treatment Period 2

Detailed description: TP1: All eligible subjects entered TP1 to receive 12-weeks of open-label secukinumab at a dose predicted to achieve secukinumab serum levels equivalent to adults administered a 150 mg dose regimen. Secukinumab was administered s.c. weekly for the first 4 weeks (Baseline, Weeks 1, 2, 3, 4) and then every 4 weeks thereafter. Clinical response (JIA ACR 30) was assessed at Week 12. Responders advanced to TP2 and non-responders exited the trial (early termination visit and entered into the Post-treatment follow-up period).

TP2: Subjects who were a responder (JIA ACR 30) at Week 12 entered the double-blind withdrawal TP2 and were randomized 1:1 to either secukinumab or placebo on that visit and then every 4 weeks, until either experiencing a disease flare or completion of TP2. TP2 was event driven and was planned to be closed when 33 subjects experienced a disease flare as per JIA definition. Alternatively, the study could be closed when all subjects reached the total study duration of 104 Weeks and therefore subjects who did not experience a disease flare remained in TP2 for the duration of the study and completed the study without entering into TP3

TP3: Subjects experiencing a disease flare in TP2 immediately entered TP3 to receive openlabel secukinumab every 4 weeks until total study duration of 104 weeks for that subject was achieved.

Post-treatment follow-up: The post-treatment follow-up period (lasting 12 weeks from the last study drug administration) was required for all subjects, unless they qualified and entered the secukinumab extension trial. All subjects were expected to participate in the post-treatment follow up period, except for those entering the extension study.

Eligibility criteria: Inclusion Criteria:

1. Confirmed diagnosis of Enthesitis-related arthritis (ERA) or Juvenile psoriatic arthritis (JPsA) according to the International League of Associations for Rheumatology (ILAR) classification criteria of at least 6 months duration.
2. Active disease (ERA or JPsA) defined as having both:

   * at least 3 active joints
   * at least 1 site of active enthesitis at baseline or documented by history.
3. Inadequate response (at least 1 month) or intolerance to at least 1 nonsteroidal anti-inflammatory drugs(NSAID)
4. Inadequate response (at least 2 months) or intolerance to at least 1 Disease-modifying antirheumatic drugs (DMARD)
5. No concomitant use of second line agents such as disease-modifying and/or immunosuppressive drugs.

Exclusion Criteria:

1. Patients fulfilling any ILAR diagnostic JIA category other than ERA or JPsA.
2. Patients who have ever received biologic immunomodulating agents
3. Patients taking any non-biologic DMARD except for MTX (or sulfasalazine for ERA patients only).
4. Patients with active uncontrolled inflammatory bowel disease or active uncontrolled uveitis.

Other protocol-defined inclusion/exclusion criteria apply.

Primary outcomes:
measure: Number of Participants Experiencing a Flare During Treatment Period 2
timeFrame: From Week 12 until max Week 104
Secondary outcomes:
measure: Percent of Participants With Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology (ACR) 30/50/70/90/100 Response at Week 12 - by JIA Category
timeFrame: baseline, week 12
measure: Percent of Participants With Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology (ACR) 30/50/70/90/100 Response at Week 12 - Total
timeFrame: baseline, week 12
measure: Percent Change From Baseline for JIA ACR Core Components in TP1
timeFrame: baseline, week 12
measure: Percent Change in C-reactive Protein Standardized Value (mg/L)
timeFrame: baseline, week 12
measure: Change From Baseline Juvenile Arthritis Disease Activity Score (JADAS) Score
timeFrame: 12 weeks
measure: Change From Baseline in Total Enthesitis Events - TP1 (FAS1)
timeFrame: Baseline and week 12
measure: Change From Baseline in Total Dactylitis Count
timeFrame: baseline, week 12
measure: Number of Participants With Anti-secukinumab Anitbodies
timeFrame: 104 weeks
measure: Secukinumab Serum Concentration
timeFrame: baseline, week 12
measure: Number of Participants With Inactive Disease Status for All Subjects - TP1 (FAS1)
timeFrame: week 12
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Novartis Investigative Site
state: California
city: Boise
country: United States
facility: Novartis Investigative Site
state: Idaho
city: Cincinnati
country: United States
facility: Novartis Investigative Site
state: Ohio
city: Portland
country: United States
facility: Novartis Investigative Site
state: Oregon
city: Bruxelles
country: Belgium
facility: Novartis Investigative Site
city: Gent
country: Belgium
facility: Novartis Investigative Site
city: Laeken
country: Belgium
facility: Novartis Investigative Site
city: Berlin
country: Germany
facility: Novartis Investigative Site
city: Freiburg
country: Germany
facility: Novartis Investigative Site
city: Hamburg
country: Germany
facility: Novartis Investigative Site
city: Saint Augustin
country: Germany
facility: Novartis Investigative Site
city: Genova
country: Italy
facility: Novartis Investigative Site
state: GE
city: Napoli
country: Italy
facility: Novartis Investigative Site
city: Krakow
country: Poland
facility: Novartis Investigative Site
city: Ekaterinburg
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: Voronezh
country: Russian Federation
facility: Novartis Investigative Site
city: Cape Town
country: South Africa
facility: Novartis Investigative Site
city: Panorama
country: South Africa
facility: Novartis Investigative Site
city: Santiago de Compostela
country: Spain
facility: Novartis Investigative Site
state: Galicia
city: Valencia
country: Spain
facility: Novartis Investigative Site
city: Istanbul
country: Turkey
facility: Novartis Investigative Site
state: Halkali
city: Istanbul
country: Turkey
facility: Novartis Investigative Site
state: TUR
city: Ankara
country: Turkey
facility: Novartis Investigative Site
city: Istanbul
country: Turkey
facility: Novartis Investigative Site
city: Bristol
country: United Kingdom
facility: Novartis Investigative Site
city: Glasgow
country: United Kingdom
facility: Novartis Investigative Site
city: Liverpool
country: United Kingdom
facility: Novartis Investigative Site
city: London
country: United Kingdom
facility: Novartis Investigative Site
city: Nottingham
country: United Kingdom
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References:
citation: Brunner HI, Foeldvari I, Alexeeva E, Ayaz NA, Calvo Penades I, Kasapcopur O, Chasnyk VG, Hufnagel M, Zuber Z, Schulert G, Ozen S, Rakhimyanova A, Ramanan A, Scott C, Sozeri B, Zholobova E, Martin R, Zhu X, Whelan S, Pricop L, Martini A, Lovell D, Ruperto N; Paediatric Rheumatology INternational Trials Organization (PRINTO) and Pediatric Rheumatology Collaborative Study Group (PRCSG). Secukinumab in enthesitis-related arthritis and juvenile psoriatic arthritis: a randomised, double-blind, placebo-controlled, treatment withdrawal, phase 3 trial. Ann Rheum Dis. 2023 Jan;82(1):154-160. doi: 10.1136/ard-2022-222849. Epub 2022 Aug 12.