A PHASE 3, MULTI-CENTER, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED STUDY TO ASSESS THE EFFICACY AND SAFETY OF APREMILAST (CC-10004) IN PEDIATRIC SUBJECTS FROM 6 THROUGH 17 YEARS WITH MODERATE TO SEVERE PLAQUE PSORIASIS
Overview
- Phase
- Phase 3
- Intervention
- Apremilast (CC-10004)
- Conditions
- Psoriasis
- Sponsor
- Amgen
- Enrollment
- 245
- Locations
- 99
- Primary Endpoint
- Percentage of Participants With a Static Physician Global Assessment (sPGA) Response at Week 16
- Status
- Completed
- Last Updated
- last year
Overview
Brief Summary
This is a Phase 3, multicenter, randomized, placebo-controlled, double-blind study of the efficacy and safety of apremilast (CC-10004) in pediatric subjects with moderate to severe plaque psoriasis.
At least 230 pediatric subjects (ages 6 through 17 years) will be randomized 2:1 to receive either apremilast or placebo for the first 16 weeks and then all subjects will receive apremilast during the 36 week Extension Phase for a total of 52 weeks. Randomization to apremilast arm or placebo arm will be stratified by age group (6 to 11 years or 12 to 17 years). Subjects will receive apremilast treatment of either 20 mg twice daily (BID) or 30 mg BID, depending on weight. This Phase 3 study is being conducted to evaluate the safety and efficacy of apremilast in the treatment of pediatric subjects.
Detailed Description
Treatment will be assigned by weight with subjects 20 kg to \< 50 kg receiving apremilast 20 mg BID or placebo BID and subjects ≥ 50 kg receiving apremilast 30 mg BID or placebo BID. Total study duration is up to 71 weeks. Subjects completing all 52 weeks of the treatment and extension phase will be able to enter the Long-term study. Subjects not entering the Long-term study will return for 3 observational follow-up visits, 4, 8 and 14 weeks after last dose of study drug.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Males or female subjects 6 to 17 years of age, inclusive, at the time the informed consent form is signed by the legal guardian
- •Subjects must have a weight of ≥ 20 kg
- •Diagnosis of chronic plaque psoriasis for at least 6 months prior to Screening.
- •Has moderate to severe plaque psoriasis at Screening and Baseline as defined by:
- •PASI score ≥ 12; and
- •Body surface area (BSA) ≥ 10%; and
- •sPGA ≥ 3 (moderate to severe)
- •Disease inadequately controlled by or inappropriate for topical therapy for psoriasis
- •Candidate for systemic therapy or phototherapy
Exclusion Criteria
- •Guttate, erythrodermic, or pustular psoriasis at Screening and Baseline
- •Psoriasis flare or rebound within 4 weeks prior to Screening
- •Prior history of suicide attempt at any time in the subject's lifetime prior to Screening or randomization in the study, or major psychiatric illness requiring hospitalization within 3 years prior to signing the assent and informed consent
- •Answer "Yes" to any question on the Columbia-Suicide Severity Rating Scale during Screening or at Baseline
- •Current or planned concurrent use of the following therapies that may have a possible effect on psoriasis
- •a. Topical therapy within 2 weeks prior to randomization (including but not limited to topical corticosteroids, topical retinoid or vitamin D analog preparations, tacrolimus, pimecrolimus, or anthralin/dithranol)
- •Exceptions\*:
- •i. Low potency or weak corticosteroids (please refer to the Investigators' Manual) will be allowed as background therapy for treatment of the face, axillae and groin in accordance with manufacturer's suggested usage ii. Unmedicated skin moisturizer (eg, Eucerin®) will also be permitted for body lesions
- •\*Subjects should not use these topical treatments within 24 hours prior to the clinic visit.
- •b. Conventional systemic therapy for psoriasis within 4 weeks prior to randomization c. Phototherapy treatment (ie, ultraviolet B \[UVB\], PUVA) within 4 weeks prior to randomization d. Biologic therapy within 4 weeks prior to randomization or 5 PK/PD half-lives (whichever is longer).
Arms & Interventions
Administration of Apremilast (CC-10004) - 30mg
Apremilast 30mg Twice Daily (BID)
Intervention: Apremilast (CC-10004)
Administration of Placebo
Placebo tablet Twice Daily (BID)
Intervention: Placebo
Administration of Apremilast (CC-10004) - 20mg
Apremilast 20mg Twice Daily (BID)
Intervention: Apremilast (CC-10004)
Outcomes
Primary Outcomes
Percentage of Participants With a Static Physician Global Assessment (sPGA) Response at Week 16
Time Frame: Baseline to Week 16
The sPGA is the assessment by the Investigator of the overall disease severity of plaque psoriasis at the time of evaluation. The sPGA is a 5-point scale ranging from 0 (clear) to 4 (severe), incorporating an assessment of the severity of the three primary signs of the disease: erythema, scaling and plaque elevation. The results presented are for the percentage of participants with a sPGA response. An sPGA response was defined as a score of clear (0) or almost clear (1) with at least a 2-point reduction from baseline at Week 16.
Secondary Outcomes
- Percentage Change From Baseline in Body Surface Area (BSA) Affected by Psoriasis at Week 16(Baseline and Week 16)
- Percentage Change From Baseline in Total PASI Score at Week 16(Baseline and Week 16)
- Number of Participants Who Experienced a TEAE During the Apremilast Exposure Period(52 weeks)
- Number of Participants Who Experienced a TRAE During the Apremilast Exposure Period(52 weeks)
- Percentage of Participants Who Achieved At Least 75% Reduction in Psoriasis Area Severity Index (PASI-75) From Baseline at Week 16(Baseline and Week 16)
- Percentage of Participants Who Achieved At Least 50% Reduction in Psoriasis Area Severity Index (PASI-50) From Baseline at Week 16(Baseline and Week 16)
- Percentage of Participants Who Achieved a Children's Dermatology Life Quality Index (CDLQI) Score of 0 or 1 at Week 16(Week 16)
- Change From Baseline in CDLQI Score at Week 16(Baseline and Week 16)
- Number of Participants With Diarrhea During the Apremilast Exposure Period(Day 1 up to approximately 365 days)
- Number of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE) During the Placebo-controlled Phase(16 weeks)
- Number of Participants With Diarrhea Symptoms During the Apremilast Exposure Period(Day 1 up to approximately 365 days)
- Number of Female Participants at Stage I-V of Sexual Development Per Tanner Staging of Sexual Development(Week 52)
- Mean Height of Participants During the Placebo-controlled Phase(Baseline and Week 16)
- Mean Body Mass Index (BMI) of Participants During the Placebo-controlled Phase(Baseline and Week 16)
- Number of Participants Who Experienced a Treatment-related Adverse Event (TRAE) During the Placebo-controlled Phase(16 weeks)
- Number of Participants With Suicidal Ideation or Behavior Per the C-SSRS During the Apremilast-extension Phase(Week 16 to Week 52)
- Mean Height of Participants During the Apremilast Exposure Period(Baseline and Week 52)
- Number of Participants Who Experienced a Treatment-emergent Serious Adverse Event (TESAE) During the Placebo-controlled Phase(16 weeks)
- Number of Participants Who Experienced a TESAE During the Apremilast Exposure Period(52 weeks)
- Number of Participants With Diarrhea During the Placebo-controlled Phase(Up to approximately 113 days)
- Mean BMI of Participants During the Apremilast Exposure Period(Baseline and Week 52)
- Number of Participants Who Experienced a Psoriasis Flare During the Placebo-controlled Phase(16 weeks)
- Number of Participants Who Experienced a Psoriasis Flare During the Apremilast Exposure Period(52 weeks)
- Number of Participants Who Experienced a Psoriasis Rebound(14 weeks post last dose (max mean treatment duration in placebo-controlled phase was 15.3 weeks, and 41.9 weeks in the apremilast-exposure period))
- Number of Participants With Diarrhea Symptoms During the Placebo-controlled Phase(Up to approximately 113 days)
- Number of Male Participants at Stage I-V of Sexual Development Per Tanner Staging of Sexual Development(Week 52)
- Mean Body Weight of Participants During the Apremilast Exposure Period(Baseline and Week 52)
- Mean Body Weight of Participants During the Placebo-controlled Phase(Baseline and Week 16)
- Number of Participants With Suicidal Ideation or Behavior Per the Columbia-Suicide Severity Rating Scale (C-SSRS) During the Placebo-controlled Phase(16 weeks)