Clinical Trials/NCT02576678

NCT02576678

Completed

Phase 2

A Phase 2, Multicenter, Open-Label Study to Assess the Safety, Tolerability and Pharmacokinetics of Apremilast (CC-10004) in Pediatric Subjects With Moderate to Severe Plaque Psoriasis

Amgen18 sites in 4 countries42 target enrollmentOctober 13, 2015

ConditionsPsoriasis

InterventionsApremilast

DrugsApremilast

Overview

Phase: Phase 2
Intervention: Apremilast
Conditions: Psoriasis
Sponsor: Amgen
Enrollment: 42
Locations: 18
Primary Endpoint: Area Under the Plasma Concentration-time Curve From Time Zero to the Last Measurable Concentration of Apremilast (AUC0-t)
Status: Completed
Last Updated: 5 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

This is a Phase 2, multicenter, open-label study in subjects with moderate to severe plaque psoriasis aged 6 to 17 years, inclusive, intended to assess the safety, tolerability, and PK of apremilast with 2 weeks of oral apremilast treatment followed by a 48-week extension of apremilast treatment. Moderate to severe plaque psoriasis is defined as Psoriasis Area Severity Index (PASI) ≥ 12, Body Surface Area (BSA) ≥ 10%, and static Physician Global Assessment (sPGA) of ≥ 3. The total study duration for each subject will last for up to a total of 107 weeks which includes screening, treatment (including the PK portion of the study and the extension treatment period), two short-term follow-up periods and a long-term follow-up period.

Detailed Description

Each subject will undergo a screening period of up to 5 weeks, a treatment period of 2 weeks with PK sample collection, and an extension treatment period of 48 weeks, to allow subjects access to apremilast treatment if medically appropriate (following the completion of the 2 week PK portion). Regardless of when they stop treatment, subjects should complete two post treatment follow-up visits at approximately 4 and 8 weeks after the last dose. All subjects should complete the final follow-up visit at Week 102 or at a timepoint 52 weeks after the last dose of apremilast was taken in subjects who have withdrawn at any time prior to Week 50. At least 32 subjects will be enrolled into this study to provide an adequate PK profile and safety assessment in subjects of different ages and body weight ranges. Subjects will be divided into 2 age groups (adolescents \[ages 12 to 17 years, inclusive\] and children \[ages 6 to 11 years, inclusive\]), with at least 16 subjects in each group. Apremilast treatment will start in older and heavier subjects. Group 1 (ages 12 to 17 years, inclusive; weight ≥ 35 kg) * The data collected from the first 8 subjects will be reviewed by an independent data monitoring committee (DMC) to determine if it is appropriate to proceed with dosing the balance of Group 1 subjects and to proceed with dosing in the Group 2 subjects. and an evaluation of these data by the DMC has been completed. Group 2 (ages 6 to 11 years, inclusive; weight ≥ 15 kg) * The dose regimens (dose strength and/or dose frequency) for these first 8 subjects will be based upon the PK and safety assessments from the first 8 subjects in Group 1. * For the remaining subjects in Group 2, the dose (dose strength and/or dose frequency) will be based upon the subject weight as determined by the PK and safety assessments. The dose strength and/or dose frequency will be adjusted for any safety concerns or for unexpected changes in exposure. In the event of a dose regimen adjustment after the second PK and safety assessment, the first 8 subjects in Group 2 will return to the site for the appropriate dosing adjustment.

Registry

clinicaltrials.gov

Start Date

October 13, 2015

End Date

July 29, 2019

Last Updated

5 years ago

Study Type

Interventional

Study Design

Single Group

Sex

All

Investigators

Sponsor

Amgen

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Subjects must satisfy all of the following criteria to be enrolled in the study:
•Male or female subjects 6 to 17 years of age, inclusive, at the time the informed consent document is signed by the legal guardian
•Group 1 Only: ages 12 to 17 years, inclusive, and weighs ≥ 35 kg
•Group 2 Only: ages 6 to 11 years, inclusive, and weighs ≥ 15 kg
•Subject is able to swallow the apremilast tablet
•Able to sign an assent with a legal guardian who can understand and voluntarily sign an informed consent
•Able to adhere to the study visit schedule and other protocol requirements
•Must agree to withhold vaccinations during the first 2 weeks of dosing. Inactivated vaccines will be allowed during the extension treatment period
•Diagnosis of chronic plaque psoriasis for at least 6 months prior to Screening
•Have moderate to severe plaque psoriasis at Screening and Baseline as defined by:

Exclusion Criteria

•The presence of any of the following will exclude a subject from enrollment:
•History of or currently active inflammatory bowel disease
•Major concurrent medical conditions, pregnancy or lactation
•Any condition that confounds the ability to interpret data from the study
•Guttate, erythrodermic, or pustular psoriasis
•Psoriasis flare or rebound within 4 weeks prior to Screening
•Evidence of skin conditions that would interfere with clinical assessments
•History of human immunodeficiency virus infection, or positive result to hepatitis B surface antigen or hepatitis C antibodies at Screening
•Clinically significant abnormality on 12-Lead ECG at Screening
•History of active mycobacterial infection with any species (including Mycobacterium tuberculosis) within 3 years of the Screening Visit and without documentation of successful treatment

Arms & Interventions

Open label apremilast

Apremilast doses of 10-mg, 20-mg or 30-mg tablets have been selected to determine the dose range in adolescents and children with moderate to severe plaque psoriasis. These pediatric dosages are expected to achieve exposures similar to those achieved in adult psoriasis and psoriatic arthritis (PsA) subjects treated with apremilast 30 mg orally twice daily (BID). A staggered, stepwise approach by age range and weight (starting with older and heavier subjects) is considered appropriate for this first-time-in-children study. Doses for younger and lower body weight subjects will be adjusted based on safety and PK data from older and heavier subjects. Subjects will be divided into 2 age groups with at least 16 subjects in each group. Dosing within and between groups will be staggered, based on PK data collected and on a minimum of 2 weeks of safety data.

Intervention: Apremilast

Outcomes

Primary Outcomes

Area Under the Plasma Concentration-time Curve From Time Zero to the Last Measurable Concentration of Apremilast (AUC0-t)

Time Frame: For adolescents, a pre-dose sample prior to morning dose and on Day 14 as well as at hours 1, 2, 3, 5, 8 and 12 post dose; for the children, samples were collected 2 hours at predose (prior to morning dose) and at 2, 5 and 12 hours post morning dose.

Area under the plasma concentration-time curve from time zero to the last quantifiable time point and was calculated using non-compartmental methods, plasma concentrations and actual blood sampling times from the intensive sampling schedule.

Time to Maximum Plasma Concentration (Tmax) of Apremilast

Time to maximum observed plasma concentration obtained directly from the observed concentration versus time data. PK parameters were calculated using non-compartmental methods, plasma concentrations and actual blood sampling times from the intensive sampling schedule.

Terminal Phase Elimination Half-Life

Terminal-phase elimination half-life (t ½). PK parameters were calculated using non-compartmental methods, plasma concentrations and actual blood sampling times from the intensive sampling schedule.

Number of Participants With Treatment Emergent Adverse Events (TEAEs)

Time Frame: From first dose of apremilast until 28 days after the last dose; up to 29 July 2019; median treatment duration for adolescents apremilast 20 mg and 30 mg was 50.00 and 50.57 weeks respectively and for children was 50.00 weeks.

A TEAE is an adverse event with a start date on or after the date of the first dose of apremilast and no later than 28 days after the last dose of apremilast. An adverse event is any noxious, unintended, or untoward medical occurrence that may appear or worsen in a subject during the course of a study. It may be a new intercurrent illness, a worsening concomitant illness, an injury, or any concomitant impairment of the subject's health, including laboratory test values, regardless of etiology. A serious AE is any untoward AE that results in death, is life threatening, requires inpatient hospitalization or prolongation of existing hospitalization or in persistent or significant disability/incapacity, results in a congenital anomaly/birth defect or constitutes an important medical event. The investigator assessment of severity/intensity of an event was defined as mild, moderate or severe.

Area Under the Plasma Concentration-time Curve From Time Zero to 12 Hours Post Dose of Apremilast (AUC0-12)

Area under the plasma concentration-time curve from time zero to the 12 hours post dose was calculated using non-compartmental methods, plasma concentrations and actual blood sampling times from the intensive sampling schedule.

Apparent Total Plasma Clearance When Dosed Orally (CL/F) for Apremilast

Apparent total plasma clearance (CL/F) of apremilast was calculated using non-compartmental methods, plasma concentrations and actual blood sampling times from the intensive sampling schedule.

Maximum Observed Plasma Concentration (Cmax) of Apremilast

Maximum observed plasma concentration (Cmax) of apremilast. PK parameters were calculated using non-compartmental methods, plasma concentrations and actual blood sampling times from the intensive sampling schedule.

Apparent Total Volume of Distribution When Dosed Orally, Based on Study-State (Vss/F) or in the Terminal Phase (Vz/F)

Apparent total volume of distribution when dosed orally, based on study-state (Vss/F) or in the terminal phase (Vz/F). Pharmacokinetic parameters were calculated using non-compartmental methods, plasma concentrations and actual blood sampling times from the intensive sampling schedule.