Apremilast study in children with active oral ulcers associated with Behçet's Disease

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Amgen Inc.

Participant type

Pediatric, Patients

Age range

0-17 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Immune System Diseases [C20]

Trial duration

11 Nov 2024 → ongoing

Decision date (initial)

2023-09-08

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Amgen Inc.

External identifiers

EU CT number

2023-503436-40-00

EudraCT number

2019-002787-27

WHO UTN

U1111-1290-0646

ClinicalTrials.gov

NCT04528082

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy

To estimate the efficacy of apremilast compared to placebo in the treatment of oral ulcers in pediatric subjects from 2 to less than 18 years of age with oral ulcers associated with Behçet's Disease (BD) through week 12.

Secondary objectives 9

1. Estimate other measures of the efficacy of apremilast compared to placebo for oral ulcers in pediatric subjects (2 to less 18 years) with oral ulcers associated with BD through week 12
2. Estimate efficacy of apremilast compared to placebo in the treatment of genital ulcers in pediatric subjects (2 to less 18 years) with oral ulcers associated with BD through week 12
3. Estimate efficacy of apremilast compared to placebo for overall BD related disease activity in pediatric subjects (2 to less 18 years) with oral ulcers associated with BD through week 12.
4. Estimate effect of apremilast compared to placebo on BD manifestations (other than oral and genital ulcers) in pediatric subjects (2 to less 18 years) with oral ulcers associated with BD through week 12.
5. Estimate effect of apremilast compared to placebo on health-related quality of life (HRQoL) in pediatric subjects (2 to less 18 years) with oral ulcers associated with BD.
6. Estimate safety and tolerability of apremilast compared to placebo, in pediatric subjects (2 to less 18 years) with oral ulcers associated with BD.
7. Characterize the pharmacokinetics of apremilast in pediatric subjects (2 to less 18 years) with oral ulcers associated with BD.
8. Evaluate the taste and acceptability of apremilast tablet and liquid formulations in pediatric subjects (2 to less 18 years) with oral ulcers associated with BD.
9. Estimate worsening of BD requiring protocol-prohibited medication in pediatric subjects (2 to less 18 years) with oral ulcers associated with BD.

Conditions and MedDRA coding

Behcet's disease

Study design 1 period

Regulatory references

Scientific advice from competent authorities

European Medicines Agency

EMA paediatric investigation plan (PIP)

EMEA-000715-PIP05-13

Plan to share 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. Information on IPD sharing Access Criteria, Time Frame and Supporting Information Type is available at ClinicalTrials.gov (https://clinicaltrials.gov/study/NCT02307513) and at Amgen Clinical Trials portal (http://www.amgen.com/datasharing).

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

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 more or equal to 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.

Exclusion criteria 5

1. 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, eningoencephalitis) 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; -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. 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 would 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.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Area under the curve (AUC) for the number of oral ulcers from baseline (week 0) to week 12

Secondary endpoints 15

1. Number of oral ulcers from baseline (week 0) to week 12
2. Change in the pain of oral ulcers as measured by a visual analog scale (VAS) from baseline (week 0) to week 12 in subjects 5 years of age and older
3. Complete response rate for oral ulcers defined as the proportion of subjects who are oral ulcer free at week 12
4. Proportion of subjects at week 12 whose number of oral ulcers is reduced by greater than or equal to 50% from week 0
5. 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
6. Change from week 0 to week 12 in disease activity as measured by Behçet’s Disease Current Activity (BDCAF) scores
7. 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)
8. Change from baseline (week 0) to week 12 on the Short form Survey (SF-10)
9. Type, frequency, severity, and relationship to investigational product of adverse events (including malignancies and serious/systemic infections), changes in clinical laboratory parameters, 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
10. 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
11. Tanner staging of sexual development assessment of sexual maturity at week 0 and week 52 (or early termination)
12. Body weight, height, and BMI at week 0 (baseline) through week 52 and the 30 day posttreatment safety follow-up visit
13. Plasma concentrations of apremilast will be summarized by visit and dosing regimen from week 2 and to week 52
14. Taste and acceptability at week 0 and week 2
15. Proportion of subject who require protocol-prohibited medications due to worsening of BD from week 0 through week 12

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 4

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Amgen Inc.

Sponsor organisation

Amgen Inc.

Address

1 Amgen Center Drive

City

Thousand Oaks

Postcode

91320-1799

Country

United States

Scientific contact point

Organisation

Amgen Inc.

Contact name

Medical Information

Public contact point

Organisation

Amgen Inc.

Contact name

Medical Information

Third parties 9

Locations

4 EU/EEA countries · 17 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Oversight and notifications

Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77

Temporary halts 4 · Art. 38 CTR

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 90 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

8 submissions — initial application plus substantial / non-substantial modifications