Apremilast Pediatric Study in Children With Active Oral Ulcers Associated With Behçet's Disease (BEAN)

A Phase 3, Multicenter, Double-blind, Randomized, Placebo-controlled, Parallel Group Study, Followed by an Active Treatment Phase to Evaluate the Efficacy and Safety of Apremilast in Children From 2 to Less Than 18 Years of Age With Active Oral Ulcers Associated With Behçet's Disease (BEAN)

The aim of this study is to estimate the efficacy of apremilast compared to placebo in the treatment of oral ulcers in pediatric participants from 2 to < 18 years of age with oral ulcers associated with Behçet's disease (BD) through week 12.

Study Overview

• Status: Recruiting
• Conditions: Behçet Disease
• Intervention / Treatment: Drug: Apremilast; Drug: Placebo

• Study Type: Interventional
• Enrollment (Estimated): 60
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Amgen Call Center; Phone Number: 866-572-6436; Email: medinfo@amgen.com

Study Locations

• France
  • Bron cedex, France, 69677
    • Recruiting
    • Hospices Civils de Lyon Hopital Femme Mere Enfant
  • Paris, France, 75019
    • Recruiting
    • Hôpital Robert Debré
  • Paris, France, 75015
    • Recruiting
    • Hôpital Necker Enfants Malades
• Greece
  • Athens, Greece, 12462
    • Recruiting
    • Attikon University General Hospital
  • Athens, Greece, 11527
    • Recruiting
    • Agia Sofia Children Hospital
  • Thessaloniki, Greece, 54642
    • Recruiting
    • General Hospital of Thessaloniki Ippokrateio
• Israel
  • Kfar Saba, Israel, 4428164
    • Recruiting
    • Meir Medical Center
• Italy
  • Chieti, Italy, 66100
    • Recruiting
    • Ospedale Santissima Annunziata
  • Genova, Italy, 16147
    • Recruiting
    • IRCCS Istituto Giannina Gaslini
  • Milano, Italy, 20122
    • Recruiting
    • Azienda Socio Sanitaria Territoriale Centro Specialistico Ortopedico Traumatologico Gaetano Pini
  • Roma, Italy, 00165
    • Recruiting
    • IRCCS Ospedale Pediatrico Bambino Gesù
• Spain
  • Madrid, Spain, 28034
    • Recruiting
    • Hospital Universitario Ramon y Cajal
  • Madrid, Spain, 28046
    • Recruiting
    • Hospital Universitario La Paz
  • Andalucía
    • Sevilla, Andalucía, Spain, 41013
      • Recruiting
      • Hospital Universitario Virgen del Rocio
  • Cataluña
    • Barcelona, Cataluña, Spain, 08035
      • Recruiting
      • Hospital Universitari Vall d Hebron
    • Esplugues de Llobregat, Cataluña, Spain, 08950
      • Recruiting
      • Hospital Sant Joan de Déu
  • Comunidad Valenciana
    • Valencia, Comunidad Valenciana, Spain, 46026
      • Recruiting
      • Hospital Universitari I Politecnic La Fe
• Switzerland
  • Lausanne, Switzerland, 1011
    • Terminated
    • Centre Hospitalier Universitaire Vaudois
• Turkey
  • Ankara, Turkey, 06100
    • Recruiting
    • Hacettepe Universitesi Tip Fakultesi Hastanesi
  • Istanbul, Turkey, 34093
    • Recruiting
    • Istanbul Universitesi Istanbul Tip Fakultesi Hastanesi
  • Istanbul, Turkey, 34098
    • Recruiting
    • Istanbul Universitesi Cerrahpasa Tip Fakultesi
  • Istanbul, Turkey, 34764
    • Recruiting
    • Umraniye Egitim ve Arastirma Hastanesi
  • Izmir, Turkey, 35330
    • Recruiting
    • Dokuz Eylul Universitesi Tip Fakultesi Hastanesi
  • Kayseri, Turkey, 38030
    • Recruiting
    • Erciyes Universitesi Tip Fakultesi Hastanesi
• United Kingdom
  • Birmingham, United Kingdom, B4 6NH
    • Recruiting
    • Birmingham Childrens Hospital
  • Liverpool, United Kingdom, L12 2AP
    • Recruiting
    • Alder Hey Childrens Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 years to 17 years (Child)
• Accepts Healthy Volunteers: No

Description

Key Inclusion Criteria

• Male or Female participants 2 to < 18 years of age at randomization.
• Diagnosed with behçet's disease (BD) meeting the International Study Group for Behçet Disease (ISGBD) criteria at any time prior to the screening visit.
• Oral ulcers that occurred ≥ 3 times within the 12-month period prior to the screening visit.
• Participant must have ≥ 2 oral ulcers at both the screening visit and on day 1.
• Participant has had prior treatment with ≥ 1 non-biologic BD therapy, such as, but not limited to, topical corticosteroids or systemic treatment.

Key Exclusion Criteria

• Behcet's disease-related active major organ involvement - pulmonary (eg, pulmonary artery aneurysm), vascular (eg, thrombophlebitis), gastrointestinal (eg, ulcers along the gastrointestinal tract), and central nervous system (CNS) (eg, meningoencephalitis) manifestations, and ocular lesions (eg, uveitis) requiring immunosuppressive therapy; however:

  • Previous major organ involvement is allowed if it occurred ≥1 year prior to the screening visit and is not active at time of enrollment
  • Participants with mild BD-related ocular lesions not requiring systemic immunosuppressive therapy are allowed
  • Participants with BD-related arthritis and BD-skin manifestations are also allowed.
• Previous exposure to biologic therapies for the treatment of BD oral ulcers, previous biologic exposure is allowed for other indications (including other manifestations of BD).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Apremilast; Participants will receive apremilast orally in the double-blind 12 week treatment phase. Then the participants will continue to receive apremilast in the active 40 weeks treatment phase.	Drug: Apremilast; Participants will receive apremilast orally.; Other Names: Otezla®
Placebo Comparator: Placebo to Apremilast; Participants will receive the matching placebo orally in the double-blind 12 week treatment phase. Then the participants will receive apremilast in the active 40 weeks treatment phase.	Drug: Apremilast; Participants will receive apremilast orally.; Other Names: Otezla®; Drug: Placebo; Participants will receive the matching placebo orally.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Area Under the Curve for the Number of Oral Ulcers from Week 0 Through Week 12 (AUCw0-12)	Week 0 to Week 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Oral Ulcers from Week 0 to Week 12		Week 0 to Week 12
Change from Week 0 to Week 12 in the Pain of Oral Ulcers	Pain of oral ulcers will be measured by a visual analog scale (VAS). The participants will be asked to place a vertical line on a 100 mm VAS at the point that represents the severity of oral ulcer pain. The scale will range from "no pain" (left hand boundary) to "worst possible pain" (right hand boundary).	Week 0 to Week 12
Complete Response Rate for Oral Ulcers	Complete response rate for oral ulcers is defined as the proportion of participants who are oral ulcer free at Week 12.	Week 12
Proportion of Participants at Week 12 Whose Number of Oral Ulcers is Reduced by Greater Than or Equal to 50% from Week 0		Week 0 to Week 12
Complete Response Rate for Genital Ulcers	Complete response rate for genital ulcers is defined as the proportion of participants (with genital ulcers at week 0) who are genital ulcer free at Week 12.	Week 12
Change from Week 0 to Week 12 in Disease Activity	Disease activity is measured by Behçet's Disease Current Activity (BDCAF) scores. The BDCAF consists of 3 component scores: the Behçet's Disease Current Activity Index (BDCAI) score, the Patient's Perception of Disease Activity, and the Clinician's Overall Perception of Disease Activity. The BDCAI score ranges from 0 to 12. A higher score indicates higher level of disease activity (worsening), and a negative change from baseline indicates improvement. The Patient's Perception of Disease Activity and the Clinician's Overall Perception of Disease Activity were assessed by the subject and the clinician, respectively, using a scale of 1 to 7, where a higher score indicates a higher level of disease activity.	Week 0 to Week 12
Proportion of Participants at Week 12 Who Have New-onset or Recurrence of Behçet's-related Manifestations (Other than Oral and Genital Ulcers)		Week 12
Change from Week 0 to Week 12 on the Short Form Survey (SF-10)	The SF-10 Health Survey for Children is a parent-completed survey that contains 10 questions adapted from the Child Health Questionnaire. The SF-10 is intended to produce physical and psychosocial health summary measures. Each of the 10 questions responses is scored with a point value from 1 to 6 (1 is the worst possible condition and 6 is the best possible condition). The SF-10 physical and psychosocial measures are scored such that higher scores indicate more favorable functioning.	Week 0 to Week 12
Number of Participants with a Treatment-emergent Adverse Event		Up to Week 56
Occurrence, Severity, and Frequency of Suicide/Suicide-related Ideations and Behaviors as Assessed by 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 Week 0 to Week 52 in Tanner Staging	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.	Week 0 to Week 52
Change in Body Weight Measurements		Week 0 to Week 56
Change in Height Measurements		Week 0 to Week 56
Change in Body Mass Index (BMI)	BMI assessed as weight/(height/100)^2	Week 0 to Week 56
Plasma Concentrations of Apremilast		Up to Week 52
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.	Week 0 and Week 2
Proportion of Participants Who Require Protocol-prohibited Medications due to Worsening of Behçet's Disease		Week 0 to Week 12

Collaborators and Investigators

• Sponsor: Amgen
• Investigators: Study Director: MD, Amgen

Publications and helpful links

Helpful Links

• AmgenTrials clinical trials website

Study record dates

Study Major Dates

• Study Start (Actual): September 9, 2021
• Primary Completion (Estimated): August 23, 2027
• Study Completion (Estimated): July 1, 2028

Study Registration Dates

• First Submitted: August 24, 2020
• First Submitted That Met QC Criteria: August 24, 2020
• First Posted (Actual): August 27, 2020

Study Record Updates

• Last Update Posted (Estimated): December 8, 2023
• Last Update Submitted That Met QC Criteria: December 6, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Keywords: Apremilast; Behçet's Disease; Oral ulcers
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Skin Diseases; Eye Diseases; Genetic Diseases, Inborn; Stomatognathic Diseases; Mouth Diseases; Uveitis, Anterior; Panuveitis; Uveitis; Uveal Diseases; Vasculitis; Hereditary Autoinflammatory Diseases; Skin Diseases, Genetic; Skin Diseases, Vascular; Behcet Syndrome; Oral Ulcer; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Phosphodiesterase Inhibitors; Phosphodiesterase 4 Inhibitors; Apremilast
• Other Study ID Numbers: 20190530; 2019-002787-27 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request.
• IPD Sharing 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.
• IPD Sharing 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.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes