A Study of Safety, Tolerability and Pharmacokinetics of Apremilast (CC-10004) in Pediatric Subjects With Moderate to Severe Plaque Psoriasis

NCT02576678 | Completed Phase 2 Results DMC

• 1 other identifier: CC-10004-PPSO-001
• Study Type: interventional
• Target: 42
• Locations: 4 countries
• Sites: 18

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.

Conditions

Psoriasis

Keywords

Psoriasis; Moderate to Severe Plaque Psoriasis; Plaque Psoriasis; CC-10004; Apremilast; Pharmacokinetics; Open-label; Safety; Pediatric

Outcome Measures

Primary Outcomes (8)

• Number of Participants With Treatment Emergent Adverse Events (TEAEs)

  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.

  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.

• 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.

  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.

• 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.

  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 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.

  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 Measurable Concentration of Apremilast (AUC0-t)

  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.

  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.

• 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.

  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.

• 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.

  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.

• 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.

  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.

Secondary Outcomes (1)

• Taste and Acceptability of Apremilast Tablets Using the Faces Likert Scale

  Day 1

Study Arms (1)

Open label apremilast

EXPERIMENTAL

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.

Drug: Apremilast

Interventions

Apremilast DRUG

Also known as: CC-10004

Open label apremilast

Eligibility Criteria

• Age: 6 Years - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• \- 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:
• Psoriasis Area and Severity Index (PASI) score ≥ 12; and
• Body surface area (BSA) ≥ 10%; and
• Static Physician Global Assessment (sPGA) ≥ 3 (moderate to severe)
• Disease inadequately controlled by or inappropriate for topical therapy for psoriasis
• Candidate for systemic or phototherapy

You may not qualify if:

• 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
• Congenital and acquired immunodeficiencies (eg, Common Variable Immunodeficiency),immunoglobulin A deficiency
• History of recurrent significant infections
• Active infection or infection treated with antibiotic treatment within 2 weeks of first dose
• Any history of or active malignancy
• History of allergy/intolerance to any component of the investigational product, ie, apremilast, lactose monohydrate, microcrystalline cellulose, croscarmellose sodium, magnesium stearate, hypromellose 15 cP, titanium dioxide, polydextrose FCC, talc, maltodextrin, medium chain triglycerides, iron oxide red, iron oxide yellow, and iron oxide black.

Sponsors & Collaborators

• Amgen: lead

Study Sites (18)

Rady Children's Hospital

San Diego, California, 92123, United States

Location

Emory University

Atlanta, Georgia, 30322, United States

Location

Ann & Robert H. Lurie Children's Hospital of Chicago Department of Dermatology

Chicago, Illinois, 60611, United States

Location

Dundee Dermatology

West Dundee, Illinois, 60118, United States

Location

Mount Sinai, St. Luke's

New York, New York, 10025, United States

Location

Texas Dermatology and Laser Specialists

San Antonio, Texas, 78218, United States

Location

Stollery Children's Hospital

Edmonton, Alberta, T6G 2B7, Canada

Location

Nexus Clinical Research

St. John's, Newfoundland and Labrador, A1A 5E8, Canada

Location

CHU Saint-Justine

Montreal, Quebec, H3T 1C5, Canada

Location

Rheinische Friedrich-Wilhelms-Universitaet Bonn - Universitaetsklinikum Bonn

Bonn, 53127, Germany

Location

Universitatsklinikum Essen

Essen, 45147, Germany

Location

Universitatsklinikum Klinikum Frankfurt Main

Frankfurt, 60590, Germany

Location

Kinderkrankenhaus Wilhelmstift, Dermatologie

Hamburg, 22149, Germany

Location

Universitätsmedizin der Johannes Gutenberg-Universität Mainz

Mainz, 55131, Germany

Location

Muenster University Hospital (Universitätsklinikum Muenster)

Münster, 48149, Germany

Location

Hospital de la Santa Creu i Sant Pau

Barcelona, 08041, Spain

Location

Hospital Sant Joan de Deu

Esplugues de Llobregat, 08950, Spain

Location

Hospital La Paz

Madrid, 28046, Spain

Location

Related Publications (1)

• Paller AS, Hong Y, Becker EM, de Lucas R, Paris M, Zhang W, Zhang Z, Barcellona C, Maes P, Fiorillo L. Pharmacokinetics and safety of apremilast in pediatric patients with moderate to severe plaque psoriasis: Results from a phase 2 open-label study. J Am Acad Dermatol. 2020 Feb;82(2):389-397. doi: 10.1016/j.jaad.2019.08.019. Epub 2019 Aug 10.

  PMID: 31408686 RESULT

MeSH Terms

Conditions

Psoriasis

Interventions

apremilast

Condition Hierarchy (Ancestors)

Skin Diseases, Papulosquamous; Skin Diseases; Skin and Connective Tissue Diseases

Results Point of Contact

• Title: Anne McClain, Senior Manager
• Organization: Celgene Corporation

ClinicalTrialDisclosure@Celgene.com

888-260-1599

Study Officials

• MD

  Amgen

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR
• Expanded Access: Yes

Study Record Dates

• First Submitted: October 13, 2015
• First Posted: October 15, 2015
• Study Start: October 13, 2015
• Primary Completion: September 4, 2017
• Study Completion: July 29, 2019
• Last Updated: May 7, 2020
• Results First Posted: September 27, 2018

Record last verified: 2020-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: Data sharing requests relating to this study will be considered beginning 18 months after the study has ended and either 1) the product and indication have been granted marketing authorization in both the US and Europe or 2) clinical development for the product and/or indication discontinues and the data will not be submitted to regulatory authorities. There is no end date for eligibility to submit a data sharing request for this study.
• Access Criteria: Qualified researchers may submit a request containing the research objectives, the Amgen product(s) and Amgen study/studies in scope, endpoints/outcomes of interest, statistical analysis plan, data requirements, publication plan, and qualifications of the researcher(s). In general, Amgen does not grant external requests for individual patient data for the purpose of re-evaluating safety and efficacy issues already addressed in the product labelling. Requests are reviewed by a committee of internal advisors. If not approved, a Data Sharing Independent Review Panel will arbitrate and make the final decision. Upon approval, information necessary to address the research question will be provided under the terms of a data sharing agreement. This may include anonymized individual patient data and/or available supporting documents, containing fragments of analysis code where provided in analysis specifications. Further details are available at the URL below.

Locations

CA (3); US (6); DE (6); ES (3)