Apremilast Pediatric Study in Children With Active Juvenile Psoriatic Arthritis

Study Overview
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Brief Summary
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The study will aim to estimate the efficacy of apremilast compared with placebo in the treatment of juvenile psoriatic arthritis (JPsA) in pediatric participants 5 to less than 18 years of age.

Official Title
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A 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)

Conditions
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Active Juvenile Psoriatic Arthritis

Intervention / Treatment
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* Drug: Apremilast
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or Female participants 5 to < 18 years of age at the time of randomization. Participant must have a confirmed diagnosis of juvenile psoriatic arthritis (JPsA) according to the International League of Associations for Rheumatology (ILAR) Edmonton Revision (Petty, 2001) classification criteria of at least 6 months duration: Arthritis and psoriasis, OR Arthritis with at least 2 of the following: Dactylitis Nail pitting or onycholysis Psoriasis in a first-degree relative Active disease: at least 3 active joints (including distal interphalangeal joints). Inadequate response (at least 2 months) or intolerance to ≥ 1 disease-modifying anti-rheumatic drugs (DMARD), (which may include methotrexate [MTX] or biologic agents). Exclusion Criteria: Exclusions per ILAR Edmonton Revision (Edmonton, 2001) criteria for JPsA include: Arthritis in an HLA-B27-positive male with arthritis onset after 6 years of age Ankylosing spondylitis, sacroiliitis with inflammatory bowel disease, Reiter's syndrome, acute anterior uveitis, or a history of one of these disorders in a first-degree relative History of IgM rheumatoid factor on at least 2 occasions at least 3 months apart Presence of systemic juvenile idiopathic arthritis (JIA). Rheumatic autoimmune disease other than psoriatic arthritis (PsA), including, but not limited to: systemic lupus erythematosus, mixed connective tissue disease, scleroderma, polymyositis, or fibromyalgia. Prior history of or current inflammatory joint disease other than PsA (eg, gout, reactive arthritis, rheumatoid arthritis, ankylosing spondylitis, Lyme disease).

Ages Eligible for Study
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Minimum Age: 5 Years
Maximum Age: 17 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: The participants will be randomized to receive apremilast or placebo in the double-blind 16 week treatment phase. Then, the participants will all receive apremilast for a further 36 weeks in the active treatment phase. The participants not continuing to receive apremilast through the Post-Trial Access Program or Open-label Extension study will then complete the 30 days safety follow-up period after the last dose of apremilast in the active treatment phase.
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Apremilast<br>Participants will receive apremilast in the double-blind 16 week treatment phase. Then the participants will continue to receive apremilast in the active 36 weeks treatment phase. | Drug: Apremilast<br>* Participants will receive apremilast orally.<br>* Other names: Otezla®;|
| Placebo Comparator: Placebo to Apremilast<br>Participants will receive the matching placebo in the double-blind 16 week treatment phase. Then the participants will receive apremilast in the active 36 weeks treatment phase. | Drug: Apremilast<br>* Participants will receive apremilast orally.<br>* Other names: Otezla®;Drug: Placebo<br>* Participants will receive the matching placebo orally.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants who Achieve American College of Rheumatology Pediatric (ACR) Pedi 30 Response at Week 16 | The ACR Pedi 30 is defined as a minimum of 30 percent improvement from baseline in a minimum of 3 out of 6 components, with no more than 1 component worsening by >30 percent. The ACR Pedi consists of 6 core criteria: physician global assessment (PGA) of disease activity (visual analog scale [VAS]) where 0 represents no disease activity and 100 represents the most disease activity assessment of overall well-being (VAS) where 0 represents very well and 100 represents very poor for overall well-being functional ability (assessed using the Childhood Health Assessment Questionnaire [CHAQ]); number of joints with active arthritis (defined as joints with swelling not caused by deformity or joints, in the absence of swelling, with limitation of passive motion accompanied by pain, tenderness, or both) number of joints with limited range of motion laboratory marker of inflammation (C-reactive protein [CRP]). | Baseline to Week 16 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from Baseline in Participants Assessment of Pain at Week 16 | The participants assessment of pain will be assessed using a visual analogue scale (VAS). Participants will be asked to place a vertical line on a 100-mm VAS where the left-hand boundary represents no pain and the right-hand boundary represents worst possible pain. | Baseline to Week 16 | 
| Number of Participants who Achieve ACR Pedi 20, ACR Pedi 50, ACR Pedi 70 and ACR Pedi 90 Response at Week 16 | The ACR Pedi 20, 50, 70 and 90 is defined as a minimum of either 20 percent, 50 percent. 70 percent or 90 percent improvement respectively from baseline in a minimum of 3 out of 6 components, with no more than 1 component worsening by >20 percent, >50 percent, >70 percent or >90 percent respectively. The ACR Pedi consists of 6 core criteria: PGA of disease activity (VAS) where 0 represents no disease activity and 100 represents the most disease activity assessment of overall well-being (VAS) where 0 represents very well and 100 represents very poor for overall well-being functional ability (assessed using the CHAQ) number of joints with active arthritis (defined as joints with swelling not caused by deformity or joints, in the absence of swelling, with limitation of passive motion accompanied by pain, tenderness, or both) 5. number of joints with limited range of motion 6. laboratory marker of inflammation (CRP). | Baseline to Week 16 | 
| Change from Baseline in the Physician Global Assessment (PGA) of Disease Activity at Week 16 | PGA of disease activity is assessed using a visual analog scale (VAS), where 0 represents no disease activity and 100 represents the most disease activity. | Baseline to Week 16 | 
| Change from Baseline in the Assessment of Overall Well-being at Week 16 | Assessment of overall well-being is assessed using a visual analog scale (VAS), where 0 represents very well and 100 represents very poor for overall well-being. This assessment can be completed by either the participant or the parent/caregiver. | Baseline to Week 16 | 
| Change from Baseline in the Number of Joints with Active Arthritis at Week 16 | Active arthritis is defined as joints with swelling not caused by deformity of joints, in the absence of swelling, with limitation of passive motion accompanied by pain, tenderness, or both. | Baseline to Week 16 | 
| Change from Baseline in the Number of Joints with Limited Range of Motion at Week 16 |  | Baseline to Week 16 | 
| Change from Baseline in the Laboratory Marker of Inflammation (C-reactive Protein) at Week 16 |  | Baseline to Week 16 | 
| Change from Baseline in Childhood Health Assessment Questionnaire (CHAQ) at Week 16 | The CHAQ will be used to assess physical ability and functional status of participants as well as their quality of life. The CHAQ consists of 20 items concerning difficulty in performing the following 8 activities of daily living: dressing and grooming, arising, eating, walking, reaching, personal hygiene, gripping, and activities. Subjects will choose from 4 responses ranging from 0 (without any difficulty) to 3 (unable to do). A lower score indicates a better outcome. The subject's/parent's/caregiver's assessment of arthritis-related pain will also be assessed on a VAS that is part of the CHAQ. | Baseline to Week 16 | 
| Change from Baseline in Juvenile Arthritis Disease Activity Score (JADAS) at Week 16 | JADAS is a composite score of participant well-being visual analog scale (VAS) score, physician global assessment (PGA) VAS score, active joint count, and laboratory marker of inflammation (C-reactive protein [CRP]). There are 4 components of the JADAS: Active joint count (71 joints) PGA (0 to 100) measured on a VAS Patient/parent global assessment of well-being (0 to 100) measured on a VAS CRP (normalized to a 0 to 10 scale) The active joint count is taken from 71 joints: Temporomandibular joints, cervical spine, glenohumeral joints, acromioclavicular joints, sternoclavicular joints, elbows, wrists, metacarpophalangeal joints, interphalangeal joints, proximal interphalangeal joints, distal interphalangeal joints, hips, subtalar joints, midfoot joints, knees and ankles . The total score is calculated by adding all 4 components of the JADAS. The score for the JADAS ranges from 0 to 101 where a lower score indicates a better outcome. | Baseline to Week 16 | 
| Number of Participants who Experience Psoriatic Arthritis (PsA) Flares at Week 16 | PsA flares are defined as more than or equal to 30 percent worsening in at least 3 of 6 American College of Rheumatology Pediatric (ACR Pedi) core set variables with a more than or equal to 30 percent improvement in not more than 1 of 6 ACR Pedi core set variables. | Baseline to Week 16 | 
| Psoriasis Area Severity Index (PASI)-75 Response at Week 16 for Participants With a Baseline Psoriasis Body Surface Area (BSA) ≥ 3 percent | PASI scores range from 0 to 72, with higher scores reflecting greater disease severity. The PASI score is determined only for subjects whose BSA involved by psoriasis is ≥3 percent. PASI scores range from 0 to 72, with higher scores reflecting greater disease severity. Erythema, thickness, and scaling are scored on a scale of 0 (none) to 4 (very severe) on the 4 anatomic regions of the body: head, trunk, upper limbs, and lower limbs. Degree of involvement on each of the 4 anatomic regions is scored on a scale of 0 (no involvement) to 6 (90 percent < 100 percent involvement). The sum of scores for erythema, thickness, and scaling is multiplied by the degree of involvement for each anatomic region, and then multiplied by a constant corresponding to the region's percentage of BSA. The resultant values for each anatomic region are then summed to yield the PASI score. | Baseline to Week 16 | 
| Number of Participants who Experience One or More Treatment-Emergent Adverse Events (TEAEs) |  | Up to Week 56 | 
| Number of Participants With Suicidal Ideation or Behaviour Assessed Via the Columbia Suicide Severity Rating Scale (C-SSRS) | The C-SSRS is an assessment tool that evaluates suicidal ideation and behavior. Number of participants with suicidal ideation or behavior is defined as the number of participants who answer yes at any time during the study (up to end of safety follow-up, Week 56) to one of the 10 categories: Category 1: Wish to be dead Category 2: Non-specific active suicidal thoughts Category 3: Active suicidal ideation with any methods (not plan) without intent to act Category 4: Active suicidal ideation with some intent to act, without specific plan Category 5: Active suicidal ideation with specific plan and intent Category 6: Preparatory acts or behavior Category 7: Aborted attempt Category 8: Interrupted attempt Category 9: Actual attempt (non-fatal) Category 10: Completed suicide | Up to Week 56 | 
| Change from Baseline in Tanner Staging at Week 52 | Tanner Staging of sexual development assessment will be used to assess sexual maturity. Tanner Staging assessment consists of 3 domains (pubic hair, breast development, and other changes) for girls and 4 domains (pubic hair, penis development, testes development, and other changes) for boys. Stages range from 1-5, with 1 indicating preadolescent and 5 adult. | Baseline to Week 52 | 
| Change from Baseline in Body Weight at Week 56 |  | Baseline to Week 56 | 
| Change from Baseline in Height at Week 56 |  | Baseline to Week 56 | 
| Change from Baseline in Body Mass Index (BMI) at Week 56 |  | Baseline to Week 56 | 
| Plasma Concentrations of Apremilast |  | Week 2: 0-5 hours post dose; Week 8: 2 hours post dose; Week 16: 4 hours post-dose; Week 28: pre dose; Week 40: pre dose; Week 52: pre dose | 
| Taste and Acceptability of Apremilast | Taste and acceptability will be assessed using a questionnaire with a 7-point faces Likert Scale, with 1 ranging from super bad to 7 super good and questions to determine whether the participants are able to take the treatment medication. | Baseline and Week 2 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Apremilast, Otezla®, Juvenile psoriatic arthritis, Inflammatory disorders