Back to resultsApremilast Pediatric Study in Children With Active Oral Ulcers Associated With Behçet's Disease (BEAN)
Primary Purpose
Behçet Disease
Status
Recruiting
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Apremilast
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Behçet Disease focused on measuring Behçet's Disease, Oral ulcers, Apremilast
Eligibility Criteria
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).
Sites / Locations
- Hospices Civils de Lyon Hopital Femme Mere EnfantRecruiting
- Hopital Necker Enfants MaladesRecruiting
- Hopital Robert DebreRecruiting
- Agia Sofia Children HospitalRecruiting
- Attikon University General HospitalRecruiting
- General Hospital of Thessaloniki IppokrateioRecruiting
- Meir Medical CenterRecruiting
- Ospedale Santissima AnnunziataRecruiting
- IRCCS Istituto Giannina GasliniRecruiting
- Azienda Socio Sanitaria Territoriale Centro Specialistico Ortopedico Traumatologico Gaetano PiniRecruiting
- IRCCS Ospedale Pediatrico Bambino GesuRecruiting
- Hospital Universitario Virgen del RocioRecruiting
- Hospital Universitari Vall d HebronRecruiting
- Hospital Sant Joan de DeuRecruiting
- Hospital Universitari i Politecnic La FeRecruiting
- Hospital Universitario Ramon y CajalRecruiting
- Hospital Universitario La PazRecruiting
- Centre Hospitalier Universitaire Vaudois
- Hacettepe Universitesi Tip FakultesiRecruiting
- Istanbul Universitesi Istanbul Tip FakultesiRecruiting
- Umraniye Egitim ve Arastirma HastanesiRecruiting
- Dokuz Eylul Tip Fakultesi Arastirma Uygulama HastanesiRecruiting
- Erciyes Universitesi Tip FakultesiRecruiting
- Birmingham Childrens HospitalRecruiting
- Alder Hey Childrens HospitalRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Apremilast
Placebo to Apremilast
Arm Description
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.
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.
Outcomes
Primary Outcome Measures
Area Under the Curve for the Number of Oral Ulcers from Week 0 Through Week 12 (AUCw0-12)
Secondary Outcome Measures
Number of Oral Ulcers from 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).
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.
Proportion of Participants at Week 12 Whose Number of Oral Ulcers is Reduced by Greater Than or Equal to 50% from Week 0
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.
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.
Proportion of Participants at Week 12 Who Have New-onset or Recurrence of Behçet's-related Manifestations (Other than Oral and Genital Ulcers)
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.
Number of Participants with a Treatment-emergent Adverse Event
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
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.
Change in Body Weight Measurements
Change in Height Measurements
Change in Body Mass Index (BMI)
BMI assessed as weight/(height/100)^2
Plasma Concentrations of Apremilast
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.
Proportion of Participants Who Require Protocol-prohibited Medications due to Worsening of Behçet's Disease
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT04528082
Brief Title
Apremilast Pediatric Study in Children With Active Oral Ulcers Associated With Behçet's Disease
Acronym
BEAN
Official Title
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)
Study Type
Interventional
2. Study Status
Record Verification Date
October 2023
Overall Recruitment Status
Recruiting
Study Start Date
September 9, 2021 (Actual)
Primary Completion Date
August 23, 2027 (Anticipated)
Study Completion Date
July 1, 2028 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Amgen
4. Oversight
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
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Behçet Disease
Keywords
Behçet's Disease, Oral ulcers, Apremilast
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Model Description
The participants will be randomized to receive apremilast or placebo in the double-blind 12 week treatment phase. Then, the participants will all receive apremilast for a further 40 weeks in the active treatment phase. The participants will then complete the 30 days safety follow-up period after the last dose of apremilast in the active treatment phase.
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
60 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Apremilast
Arm Type
Experimental
Arm Description
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.
Arm Title
Placebo to Apremilast
Arm Type
Placebo Comparator
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Apremilast
Other Intervention Name(s)
Otezla®
Intervention Description
Participants will receive apremilast orally.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Participants will receive the matching placebo orally.
Primary Outcome Measure Information:
Title
Area Under the Curve for the Number of Oral Ulcers from Week 0 Through Week 12 (AUCw0-12)
Time Frame
Week 0 to Week 12
Secondary Outcome Measure Information:
Title
Number of Oral Ulcers from Week 0 to Week 12
Time Frame
Week 0 to Week 12
Title
Change from Week 0 to Week 12 in the Pain of Oral Ulcers
Description
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).
Time Frame
Week 0 to Week 12
Title
Complete Response Rate for Oral Ulcers
Description
Complete response rate for oral ulcers is defined as the proportion of participants who are oral ulcer free at Week 12.
Time Frame
Week 12
Title
Proportion of Participants at Week 12 Whose Number of Oral Ulcers is Reduced by Greater Than or Equal to 50% from Week 0
Time Frame
Week 0 to Week 12
Title
Complete Response Rate for Genital Ulcers
Description
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.
Time Frame
Week 12
Title
Change from Week 0 to Week 12 in Disease Activity
Description
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.
Time Frame
Week 0 to Week 12
Title
Proportion of Participants at Week 12 Who Have New-onset or Recurrence of Behçet's-related Manifestations (Other than Oral and Genital Ulcers)
Time Frame
Week 12
Title
Change from Week 0 to Week 12 on the Short Form Survey (SF-10)
Description
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.
Time Frame
Week 0 to Week 12
Title
Number of Participants with a Treatment-emergent Adverse Event
Time Frame
Up to Week 56
Title
Occurrence, Severity, and Frequency of Suicide/Suicide-related Ideations and Behaviors as Assessed by the Columbia Suicide Severity Rating Scale (C-SSRS)
Description
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
Time Frame
Up to Week 56
Title
Change from Week 0 to Week 52 in Tanner Staging
Description
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.
Time Frame
Week 0 to Week 52
Title
Change in Body Weight Measurements
Time Frame
Week 0 to Week 56
Title
Change in Height Measurements
Time Frame
Week 0 to Week 56
Title
Change in Body Mass Index (BMI)
Description
BMI assessed as weight/(height/100)^2
Time Frame
Week 0 to Week 56
Title
Plasma Concentrations of Apremilast
Time Frame
Up to Week 52
Title
Taste and Acceptability of Apremilast
Description
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.
Time Frame
Week 0 and Week 2
Title
Proportion of Participants Who Require Protocol-prohibited Medications due to Worsening of Behçet's Disease
Time Frame
Week 0 to Week 12
10. Eligibility
Sex
All
Minimum Age & Unit of Time
2 Years
Maximum Age & Unit of Time
17 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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).
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Amgen Call Center
Phone
866-572-6436
Email
medinfo@amgen.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
MD
Organizational Affiliation
Amgen
Official's Role
Study Director
Facility Information:
Facility Name
Hospices Civils de Lyon Hopital Femme Mere Enfant
City
Bron cedex
ZIP/Postal Code
69677
Country
France
Individual Site Status
Recruiting
Facility Name
Hopital Necker Enfants Malades
City
Paris
ZIP/Postal Code
75015
Country
France
Individual Site Status
Recruiting
Facility Name
Hopital Robert Debre
City
Paris
ZIP/Postal Code
75019
Country
France
Individual Site Status
Recruiting
Facility Name
Agia Sofia Children Hospital
City
Athens
ZIP/Postal Code
11527
Country
Greece
Individual Site Status
Recruiting
Facility Name
Attikon University General Hospital
City
Athens
ZIP/Postal Code
12462
Country
Greece
Individual Site Status
Recruiting
Facility Name
General Hospital of Thessaloniki Ippokrateio
City
Thessaloniki
ZIP/Postal Code
54642
Country
Greece
Individual Site Status
Recruiting
Facility Name
Meir Medical Center
City
Kfar Saba
ZIP/Postal Code
4428164
Country
Israel
Individual Site Status
Recruiting
Facility Name
Ospedale Santissima Annunziata
City
Chieti
ZIP/Postal Code
66100
Country
Italy
Individual Site Status
Recruiting
Facility Name
IRCCS Istituto Giannina Gaslini
City
Genova
ZIP/Postal Code
16147
Country
Italy
Individual Site Status
Recruiting
Facility Name
Azienda Socio Sanitaria Territoriale Centro Specialistico Ortopedico Traumatologico Gaetano Pini
City
Milano
ZIP/Postal Code
20122
Country
Italy
Individual Site Status
Recruiting
Facility Name
IRCCS Ospedale Pediatrico Bambino Gesu
City
Roma
ZIP/Postal Code
00165
Country
Italy
Individual Site Status
Recruiting
Facility Name
Hospital Universitario Virgen del Rocio
City
Sevilla
State/Province
Andalucía
ZIP/Postal Code
41013
Country
Spain
Individual Site Status
Recruiting
Facility Name
Hospital Universitari Vall d Hebron
City
Barcelona
State/Province
Cataluña
ZIP/Postal Code
08035
Country
Spain
Individual Site Status
Recruiting
Facility Name
Hospital Sant Joan de Deu
City
Esplugues de Llobregat
State/Province
Cataluña
ZIP/Postal Code
08950
Country
Spain
Individual Site Status
Recruiting
Facility Name
Hospital Universitari i Politecnic La Fe
City
Valencia
State/Province
Comunidad Valenciana
ZIP/Postal Code
46026
Country
Spain
Individual Site Status
Recruiting
Facility Name
Hospital Universitario Ramon y Cajal
City
Madrid
ZIP/Postal Code
28034
Country
Spain
Individual Site Status
Recruiting
Facility Name
Hospital Universitario La Paz
City
Madrid
ZIP/Postal Code
28046
Country
Spain
Individual Site Status
Recruiting
Facility Name
Centre Hospitalier Universitaire Vaudois
City
Lausanne
ZIP/Postal Code
1011
Country
Switzerland
Individual Site Status
Terminated
Facility Name
Hacettepe Universitesi Tip Fakultesi
City
Ankara
ZIP/Postal Code
06100
Country
Turkey
Individual Site Status
Recruiting
Facility Name
Istanbul Universitesi Istanbul Tip Fakultesi
City
Istanbul
ZIP/Postal Code
34093
Country
Turkey
Individual Site Status
Recruiting
Facility Name
Umraniye Egitim ve Arastirma Hastanesi
City
Istanbul
ZIP/Postal Code
34764
Country
Turkey
Individual Site Status
Recruiting
Facility Name
Dokuz Eylul Tip Fakultesi Arastirma Uygulama Hastanesi
City
Izmir
ZIP/Postal Code
35330
Country
Turkey
Individual Site Status
Recruiting
Facility Name
Erciyes Universitesi Tip Fakultesi
City
Kayseri
ZIP/Postal Code
38030
Country
Turkey
Individual Site Status
Recruiting
Facility Name
Birmingham Childrens Hospital
City
Birmingham
ZIP/Postal Code
B4 6NH
Country
United Kingdom
Individual Site Status
Recruiting
Facility Name
Alder Hey Childrens Hospital
City
Liverpool
ZIP/Postal Code
L12 2AP
Country
United Kingdom
Individual Site Status
Recruiting
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing 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 URL
http://www.amgen.com/datasharing
Links:
URL
http://www.amgentrials.com
Description
AmgenTrials clinical trials website
Learn more about this trial
Apremilast Pediatric Study in Children With Active Oral Ulcers Associated With Behçet's Disease
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