| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Subjects with active Behçet’s Disease |
|
| E.1.1.1 | Medical condition in easily understood language |
Behçet’s Disease causes inflammation in blood vessels throughout the
body and manifests mainly as mouth or genital ulcers with eye and skin
lesions. |
|
| E.1.1.2 | Therapeutic area | Diseases [C] - Immune System Diseases [C20] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 21.1 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10004212 |
| E.1.2 | Term | Behcet's disease |
| E.1.2 | System Organ Class | 100000004866 |
|
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
| To estimate the efficacy of apremilast in pediatric subjects from 2 to less then 18 years of age with oral ulcers associated with Behçet’s Disease (BD) |
|
| E.2.2 | Secondary objectives of the trial |
Estimate other measures of the efficacy of apremilast for oral ulcers in pediatric subjects (2 to less 18 years);
Estimate efficacy of apremilast in the treatment of genital ulcers in pediatric subjects with oral ulcers;
Estimate efficacy of apremilast for overall BD related disease activity in pediatric subjects with oral ulcers;
Estimate effect of apremilast on BD manifestations (other than oral and genital ulcers) in pediatric subjects with oral ulcers;
Estimate effect of apremilast on health-related quality of life (HRQoL) in pediatric subjects with oral ulcers;
Estimate safety and tolerability of apremilast, in pediatric subjects with oral ulcers;
Characterize the pharmacokinetics of apremilast in pediatric subjects with oral ulcers;
Evaluate the taste and acceptability of apremilast tablet and liquid formulations in pediatric subjects with oral ulcers;
Estimate worsening of BD requiring protocol-prohibited medication in pediatric subjects with oral ulcers; |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1. Male or Female subjects 2 to less than 18 years of age at randomization.
2. Diagnosed with BD meeting the ISGBD criteria at any time prior to the screening visit.
3. Oral ulcers that occurred more or equal to 3 times within the 12-month period prior to the screening visit.
4. Subject must have more or equal to 2 oral ulcers at both the screening visit and on day 1.
5. Subject has had prior treatment with ≥ 1 non-biologic BD therapy, such as, but not limited to, topical corticosteroids or systemic treatment.
6. Subject is a candidate for systemic therapy for the treatment of oral ulcers.
Other protocol-defined inclusion criteria apply |
|
| E.4 | Principal exclusion criteria |
1. Behçet’s disease-related active major organ involvement – pulmonary (eg, pulmonary artery aneurysm), vascular (eg, thrombophlebitis), gastrointestinal (eg, ulcers along the gastrointestinal tract), and 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;
-Subjects with mild BD-related ocular lesions not requiring systemic immunosuppressive therapy are allowed;
- Subjects with BD-related arthritis and BD-skin manifestations are also allowed.
2. Subjects 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).
3. History or evidence of any other clinically significant disorder,
condition or disease that could pose a risk to subject safety or interfere with the study evaluation, procedures or completion.
4. Female subject who is (or plans to become) pregnant or
breastfeeding.
5. Female subject of childbearing potential unwilling to use 1 highly
effective method of contraception.
Other protocol-defined exclusion criteria apply. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| - Area under the curve (AUC) for the number of oral ulcers |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
| from baseline (week 0) to week 12 |
|
| E.5.2 | Secondary end point(s) |
- Number of oral ulcers (a);
- Change in the pain of oral ulcers as measured by a visual analog scale (VAS) (a);
- Complete response rate for oral ulcers (defined as the proportion of subjects who are oral ulcer free) (b);
- Proportion of subjects whose number of oral ulcers is reduced by more or equal to 50% (a);
- Complete response rate for genital ulcers (defined as the proportion of subjects who are genital ulcer free) (b);
- Change in disease activity as measured by Behçet’s Disease Current Activity score (a);
- Proportion of subjects who have new-onset or recurrence of Behçet’s-related manifestations (other than oral and genital ulcers) (b);
- Change on the Short form Survey (SF-10) (a);
- Number of participants who experience treatment-emergent adverse events (type, frequency, severity and relationship to apremilast) (c);
- Number of participants who experience clinically significant laboratory tests, vital sign or physical examination measurements (c);
- Occurrence, severity, and frequency of suicide/suicide-related ideations and behaviors as assessed by the Columbia-Suicide Severity Rating Scale (C-SSRS) Questionnaire (c)
- Tanner Staging Assessment of sexual maturity (d);
- Body weight, height and BMI (c);
- Plasma concentrations of apremilast (e);
- Taste and acceptability (f);
- Proportion of subject who require protocol-prohibited medications due to worsening of BD (a). |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
(a) from baseline (week 0) to week 12
(b) at week 12
(c) from baseline (week 0) to week 56
(d) from baseline (week 0) to week 52
(e) from week 2 and to week 52
(f) at baseline (week 0) and at week 2
|
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | No |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | Yes |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | Yes |
| E.6.13.1 | Other scope of the trial description |
|
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | No |
| E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | Yes |
| E.8.1.5 | Parallel group | Yes |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | No |
| E.8.2.2 | Placebo | Yes |
| E.8.2.3 | Other | No |
| E.8.2.4 | Number of treatment arms in the trial | 2 |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 3 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 36 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
|
| E.8.7 | Trial has a data monitoring committee | Yes |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 5 |
| E.8.9.1 | In the Member State concerned months | 2 |
| E.8.9.1 | In the Member State concerned days | 0 |
| E.8.9.2 | In all countries concerned by the trial years | 5 |
| E.8.9.2 | In all countries concerned by the trial months | 2 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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