Phase 3, Multicenter, Double-blind, Randomized, Placebo-controlled, Parallel Group Study to Evaluate the Efficacy, Safety and Pharmacokinetics of Apremilast in Children From 5 to Less Than 18 Years of Age With Active Juvenile Psoriatic Arthritis (PEAPOD)

Juvenile PsA is highly heterogeneous, characterized by arthritis and rash, nail
changes (including pitting, onycholysis, and oil-drop sign), and uveitis.
Juvenile PsA resembles adult PsA. However, unlike adult PsA, inflammatory
arthritis precedes skin psoriasis in about half of children with JPsA.
The Investigational study drug, Apremilast is an oral small-molecule inhibitor
of phosphodiesterase 4 (PDE4) specific for cyclic adenosine monophosphate
(cAMP). PDE4 inhibition results in increased intracellular cAMP levels, which
in turn modulates a network of pro- and anti
inflammatory mediators. Through targeted PDE4 inhibition, apremilast reduces
the inflammatory response implicated in inflammatory and autoimmune disorders.
Apremilast, is marketed worldwide under trade name Otezla® (30mg BID). It is
approved for both psoriatic arthritis and psoriasis in 54 countries including
the United States (US) and member states of the European Union (EU).
Refer to section 2.1 and 2.2 of the protocol for more information.

This study has been transitioned to CTIS with ID 2023-503435-17-00 check the CTIS register for the current data.

Estimate the efficacy of apremilast compared with placebo in the treatment of
Juvenile Psoriatic Arthritis (JPsA) in pediatric subjects 5 to less than 18
years of age.
Refer to section 3 of the protocol for more information.

This is a phase 3, multicenter, randomized, parallel group study with a
double-blind, placebo-controlled phase followed by an active treatment phase to
assess the efficacy, safety, tolerability, and pharmacokinetics of apremilast
in subjects aged 5 to < 18 years with active Juvenile Psoriatic Arthritis
(JPsA). The total study duration for an individual subject is 62 weeks,
comprising up to a 6 week screening phase, a 52 week treatment phase (16 week
double-blind, placebo-controlled treatment phase and 36 week apremilast active
treatment phase), and a 30 day posttreatment safety follow-up phase for
subjects who are not continuing to receive apremilast through the Post-Trial
Access Program.

The double-blind, placebo-controlled treatment phase will be 16 weeks in
duration (week 0 to week 16). At least 60 evaluable subjects will be randomized
in a 2:1 ratio on day 1 to oral apremilast (tablet or liquid suspension) or
placebo (tablet or liquid suspension). The randomization will be stratified by
formulation (tablet or liquid formulation) with approximately 30 subjects
stratified to each formulation. Subjects will be dose titrated during the first
week to mitigate gastrointestinal adverse events. Subjects >= 15 kg to < 20 kg
and subjects who have a known or documented inability to swallow a tablet will
be randomized to the apremilast or placebo liquid suspension formulation.

The apremilast active treatment phase will be 36 weeks in duration (week 16 to
week 52). To maintain the blinded condition of the treatments, all subjects
will be dose titrated when they enter the active treatment phase. Subjects
assigned to apremilast treatment during the double-blind, placebo-controlled
treatment phase will continue to receive the same apremilast formulation and
original assigned dose following the dose titration. Subjects who were assigned
to placebo treatment during the double-blind, placebo-controlled treatment
phase will be switched at week 16 to receive apremilast tablet or liquid
solution with corresponding dose regimen according to baseline weight following
the dose titration.

To increase retention rates in subjects who experience limited benefit after 8
weeks of receiving investigational product (IP), considering that many or most
of these pediatric patients will wash out their prior medications at least 2
weeks before Day 1 of the study, an early escape option will be implemented.
Starting at week 8, at the discretion of the investigator, subjects
demonstrating no improvement from baseline in at least 3 of the 6 ACR Pedi core
criteria and no more than 1 of the 6 ACR Pedi core criteria with >= 30%
improvement will be eligible for early escape. Placebo-treated subjects who
early escape will be transitioned to apremilast based on their body weight (at
baseline), while apremilast-treated subjects will remain on their original
treatment assignment. All subjects participating in early escape will be
assigned as non-responders at week 16.

Upon completion of investigational product administration subjects will be
followed for safety.
The 30 (+ 3) day posttreatment follow-up phase is considered sufficient to
assess rebound effects and to evaluate safety given the half-life of apremilast
(6 to 9 hours).

Week 0 to week 16 - double-blind, placebo-controlled treatment phase:
- one group will receive apremilast depending on weight (10 mg BID for >= 15 kg
to < 20 kg, 20 mg BID for >= 20 kg to < 50 kg and 30 mg BID for >= 50 kg)
- other group will receive placebo

Week 16 to week 52 - active treatment phase:
- all patients will receive apremilast depending on weight (10 mg BID for >= 15
kg to < 20 kg, 20 mg BID for >= 20 kg to < 50 kg and 30 mg BID for >= 50 kg)

Refer to section E9 en E9a.