Behçet Disease
Conditions
Keywords
Behçet's Disease, Oral ulcers, Apremilast
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.
Interventions
DRUGApremilast
Participants will receive apremilast orally.
DRUGPlacebo
Participants will receive the matching placebo orally.
Sponsors
Amgen
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Intervention 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. Participants who complete the 52 weeks of treatment may have the opportunity to continue receiving apremilast through an open-label extension study (NCT05767047) . The participants who choose not to participate in the optional open-label, long-term study will complete the 30 days safety follow-up period after the last dose of apremilast in the active treatment phase.
Eligibility
Sex/Gender
ALL
Age
2 Years to 17 Years
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria * Male or Female participants 2 to \< 18 years of age at randomization. * Diagnosed with BD meeting the 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
* Behçet's disease-related active major organ involvement - pulmonary (eg, pulmonary artery aneurysm), vascular (eg, thrombophlebitis), gastrointestinal (eg, ulcers along the gastrointestinal tract), or CNS (eg, meningoencephalitis) manifestations, or 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).
Design outcomes
Primary
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 in Participants 5 Years of Age and Older | Week 0 to Week 12 | 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 | Week 12 | 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 | Week 0 to Week 12 | — |
| Complete Response Rate for Genital Ulcers | Week 12 | 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 | Week 0 to Week 12 | 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) | Week 12 | — |
| Change from Week 0 to Week 12 on the Short Form Survey (SF-10) | Week 0 to Week 12 | 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 | 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) | Up to Week 56 | 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 | Week 0 to Week 52 | 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 | Week 0 to Week 56 | — |
| Change in Height Measurements | Week 0 to Week 56 | — |
| Change in Body Mass Index (BMI) | Week 0 to Week 56 | BMI assessed as weight/(height/100)\^2 |
| Plasma Concentrations of Apremilast | Up to Week 52 | — |
| Taste and Acceptability of Apremilast | Week 0 and Week 2 | 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 | Week 0 to Week 12 | — |
Countries
France, Greece, Israel, Italy, Spain, Switzerland, Turkey (Türkiye), United Kingdom
Contacts
CONTACTAmgen Call Center
STUDY_DIRECTORMD
Amgen
Outcome results
None listed