Secukinumab Safety and Efficacy in Juvenile Psoriatic Arthritis (JPsA) and Enthesitis-related Arthritis (ERA)

Novartis

Status and phase: Completed; Phase 3

Conditions: Juvenile Psoriatic Arthritis; Enthesitis-related Arthritis

Treatments: Other: placebo; Drug: secukinumab

Study type: Interventional

Funder types: Industry

Identifiers

NCT03031782

CAIN457F2304

2016-003761-26 (EudraCT Number)

Details and patient eligibility

About

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

Full 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.

Enrollment: 86 patients

Sex: All

Ages: 2 to 17 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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86 participants in 2 patient groups, including a placebo group

Treatment Period 2 - active

Experimental group

Description:

secukinumab (AIN457 - pre-filled syringe) for patients with a minimum American college of Rheumatology (ACR) 30 response in Treatment Period 1

Treatment:

Drug: secukinumab

Treatment Period 2 - placebo

Placebo Comparator group

Description:

placebo comparator (matched to secukinumab treatment) for patients with a minimum American college of Rheumatology (ACR) 30 response in Treatment Period 1

Treatment:

Other: placebo