The main objective of study 20190530 is to estimate the efficacy of Apremilast compared to placebo in the treatment of oral ulcers in pediatric subjects from 2 to < 18 years of age with oral ulcers associated with BD through week 12. See protocol…
ID
Source
Brief title
Condition
- Autoimmune disorders
- Vascular disorders NEC
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary outcome of the study is to assess the area under the curve for the
number of oral ulcers from Week 0 through Week 12 (AUC W0-W12).
Secondary outcome
* Number of oral ulcers from week 0 to week 12.
* Change from week 0 to week 12 in the pain of oral ulcers as measured by a
visual analog scale (VAS)
* Complete response rate for oral ulcers defined as the proportion of subjects
who are oral ulcer free at week 12
* Proportion of subjects at week 12 whose number of oral ulcers is reduced by *
50% from week 0
* Complete response rate for genital ulcers defined as the proportion of
subjects (with genital ulcers at week 0) who are genital ulcer free at week 12.
* Change from week 0 to week 12 in disease activity as measured by Behçet*s
Disease Current Activity Form (BDCAF) scores
* Proportion of subjects at week 12 who have new-onset (ie, absent at baseline)
or recurrence (ie, with history) of Behçet*s-related manifestations (other than
oral and genital ulcers)
* Change from week 0 to week 12 on the SF-10 (10-item short form survey).
* Type, frequency, severity, and relationship to investigational product of
adverse events (including malignancies and serious/systemic infections),
clinical laboratory tests, vital signs, and physical examination from signing
of the informed consent/assent forms through week 52 and the 30 day
posttreatment safety follow-up phase.
* Occurrence, severity, and frequency of suicide/suicide-related ideations and
behaviors as assessed by the C-SSRS at select visits from week 0 through week
52 and the 30 day posttreatment safety follow-up visit.
* Tanner staging of sexual development assessment of sexual maturity at week 0
and week 52 (or early termination).
* Body weight, height, and BMI at week 0 (baseline) through week 52 and the 30
day posttreatment safety follow-up visit.
* Plasma concentrations of apremilast will be summarized by visit and dosing
regimen.
* Taste and acceptability will be assessed using a 7-point faces Likert Scale
and a parent assessment of the subject, including whether the subject was able
to swallow the tablet at week 0 and week 2.
* Proportion of subject who require protocol-prohibited medications due to
worsening of BD from week 0 through week 12.
Background summary
Behçet's Disease (BD) is a rare, multisystem inflammatory disease of unknown
origin. The oral and genital mucosa, skin and eyes are the most common organs
involved, although symptoms may vary from person to person. Apremilast works
intracellularly to modulate a network of pro-inflammatory and anti-inflammatory
mediators. The clinical development program of Apremilast for BD in adults
includes one phase 2 (BCT-001) study and a pivotal phase 3 (BCT-002) study.
The phase 2 study demonstrated a positive treatment effect of twice daily (BID)
Apremilast 30 mg in subjects with active BD with oral ulcers. In the pivotal
phase 3 study, BCT-002, BID Apremilast 30 mg met the primary endpoint for the
area under the curve (AUC) for the number of oral ulcers from week 0 through
week 12 (AUCW0-12).
See protocol section 2.1 and 2.2.
Study objective
The main objective of study 20190530 is to estimate the efficacy of Apremilast
compared to placebo in the treatment of oral ulcers in pediatric subjects from
2 to < 18 years of age with oral ulcers associated with BD through week 12.
See protocol section 3.
Study design
This is a phase 3, multicenter, randomized, parallel group study with a
double-blind, placebo-controlled phase followed by an active treatment phase to
assess the efficacy, safety, tolerability, and pharmacokinetics of apremilast
in subjects aged 2 to < 18 years with BD. The total study duration for an
individual subject is 62 weeks, comprising up to a 6 week screening phase, a 52
week treatment phase (12 week double-blind, placebo-controlled treatment phase
and 40 week apremilast active treatment phase), and a 30 day posttreatment
safety follow-up phase.
The double-blind, placebo-controlled treatment phase will be 12 weeks in
duration (week 0 to week 12). At least 60 evaluable subjects will be
randomized in a 2:1 ratio on day 1 to oral apremilast (tablet or liquid
suspension) or placebo (tablet or liquid suspension). The randomization will be
stratified by formulation (tablet or liquid formulation) with approximately 30
subjects stratified to each formulation. Subjects will be dose titrated during
the first week to mitigate gastrointestinal adverse events. Subjects * 12 kg
to < 20 kg and subjects who have a known or documented inability to swallow a
tablet will be randomized to the apremilast or placebo liquid suspension
formulation.
The apremilast active treatment phase will be 40 weeks in duration (week 12 to
week 52). To maintain the blinded condition of the treatments, all subjects
will be dose titrated when they enter the active treatment phase. Subjects
assigned to apremilast treatment during the double-blind, placebo-controlled
treatment phase will continue to receive the same apremilast formulation and
original assigned dose following the dose titration. Subjects who were
assigned to placebo treatment during the double-blind, placebo-controlled
treatment phase will be switched at week 12 to receive apremilast tablet or
liquid solution with corresponding dose regimen according to baseline weight
following the dose titration. Upon completion of investigational product
administration subjects will be followed for safety.
The 30 (+ 3) day posttreatment follow-up phase is considered sufficient to
assess rebound effects and to evaluate safety given the half-life of apremilast
(6 to 9 hours).
Intervention
Week 0 to week 12 - double-blind, placebo-controlled treatment phase:
- one group will receive apremilast depending on weight (10 mg BID for * 12 kg
to < 20 kg, 20 mg BID for * 20 kg to < 50 kg and 30 mg BID for * 50 kg)
- other group will receive placebo
Week 12 to week 52 - active treatment phase:
- all patients will receive apremilast depending on weight (10 mg BID for * 12
kg to < 20 kg, 20 mg BID for * 20 kg to < 50 kg and 30 mg BID for * 50 kg)
Study burden and risks
See section E9 en E9a.
Minervum 7061
Breda 4817 ZK
NL
Minervum 7061
Breda 4817 ZK
NL
Listed location countries
Age
Inclusion criteria
Main inclusion criteria:
- Male or Female participants 2 to < 18 years of age at randomization
- Subject must have a weight of * 12 kg at randomization
- Diagnosed with Behçet's disease meeting the International Study Group for
Behçet*s 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
- Subject must have * 2 oral ulcers at both the screening visit and on day 1
- Subject has had prior treatment with * 1 non-biologic Behçet`s disease
therapy, such as, but not limited to, topical corticosteroids or systemic
treatment
- Subject is a candidate for systemic therapy for the treatment of oral
ulcers. A candidate for systemic therapy is a subject judged by the study
Investigator as
someone whose oral ulcers are considered inappropriate for topical therapy
based on the severity of disease and extent of the affected area, or whose oral
ulcers cannot be adequately controlled by topical therapy as judged by the
Investigator.
Inclusion criteria are described in more detail in section 5.1 of the protocol.
Exclusion criteria
Main 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), and central nervous system (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.
- 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)
- Receipt of concomitant immune modulating therapy (except oral or topical
corticosteroids, which must have been tapered during screening as appropriate
and discontinued prior to randomization) within specified time based on type of
drug.
- 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.
- Female subject who is (or plans to become) pregnant or breastfeeding.
- Female subject of child bearing potential unwilling to use 1 highly effective
method of contraception.
Exclusion criteria are described in more detail in section 5.2 of the protocol.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2019-002787-27-NL |
| ClinicalTrials.gov | NCT04528082 |
| CCMO | NL75125.041.21 |