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A multi-center, single-arm study to investigate the pharmacokinetics and safety of dupilumab in male and female participants >=2 years to <12 years of age with uncontrolled chronic spontaneous urticaria (CSU)

A study to investigate the pharmacokinetics and safety of dupilumab in participants >=2 years to < 12 years of age with uncontrolled chronic spontaneous urticaria (CSU) (LIBERTY-CSU CUPIDKids)

15

Of the 15 participants enrolled, 4 (26.7%) were >=2 to <6 years old and 11 (73.3%) were >=6 to <12 years old, 73.3% were females. The majority of participants were White (60.0%), 26.7% were Asian, and 6.7% were Black or African American.

- Enrolled and exposed: 15 (200 mg every 4 weeks [Q4W]: 1, 300 mg Q4W: 4, 300 mg Q4W, 600 mg loading dose [LD]: 2, 200 mg every 2 weeks [Q2W], 400 mg LD: 8) (hereinafter in the same group order) - Completed the study treatment period: 14 (1, 3, 2, 8) - Did not complete the study treatment period: 1 (0, 1, 0, 0) All 15 participants were included in pharmacokinetic (PK), safety, and intent-to-treat (ITT) populations. ADA population included 14 participants. The PK population included all enrolled and treated participants (safety population) with at least 1 post-baseline PK result. The ADA population included all enrolled participants treated with dupilumab with at least 1 post-baseline ADA result (positive, negative or inconclusive).

Overall, dupilumab was well tolerated across all dosing regimens with 80.0% of participants experiencing at least one TEAE, and no SAEs or deaths. The most frequently reported TEAEs at the Preferred Term (PT) level, viral upper respiratory tract infection was reported by 4 participants, while influenza, nasopharyngitis, and vomiting were reported by 2 participants each.

Primary endpoint (PK population): For participants >=5 kg and <15 kg receiving dupilumab 200 mg Q4W without a LD, trough concentration (Ctrough) was 67.7 mg/L at Week 12 and 116.0 mg/L at Week 24. Participants >=15 kg and <30 kg receiving 300 mg Q4W with or without a 600 mg LD had mean (standard deviation [SD]) Ctrough of 65.5 (35.3) mg/L at Week 12, 105.0 (54.4) mg/L at Week 24. Participants >=30 kg and <60 kg receiving 200 mg Q2W with a 400 mg LD had mean (SD) Ctrough of 86.7 (19.8) mg/L at Week 12, 78.5 (31.6) mg/L at Week 24. Secondary endpoint (ADA population): Throughout the study, there were no participants with samples positive for ADA. Secondary endpoints (ITT population): A numerical improvement (reduction) in the C-DLQI in participants >=4 to <12 years of age was observed at Week 24 regardless of dosing regimen, with a mean (SD) change from baseline of -3.0 in the dupilumab 200 mg Q4W (N = 1), -6.0 in the dupilumab 300 mg Q4W (N = 1), -10.5 (3.5) in the dupilumab 300 mg Q4W, 600 mg LD (N = 2), and of -7.3 (4.3) in the dupilumab 200 mg Q4W, 400 mg LD (N = 7). For the IDQOL in participants from 2 to <4 years of age, 1 participant had available data at Week 24. For IDQOL total score, participant with available Week 24 data had a change from baseline of -3.0 points. A numerical improvement in Modified Urticaria Activity Score over 7 days (mUAS7) was observed at Week 24 regardless of dosing regimen, with a mean (SD) change from baseline of -8.0 in the dupilumab 200 mg Q4W (N = 1), -21.4 (1.9) in the dupilumab 300 mg Q4W (N = 2), -2.8 (1.8) in the dupilumab 300 mg Q4W, 600 mg LD (N = 2), and -7.8 (6.6) in the dupilumab 200 mg Q4W, 400 mg LD (N = 5). A numerical improvement (reduction) in ISS7 was observed at Week 24 regardless of dosing regimen, with a mean (SD) change from baseline of -5.0 in the dupilumab 200 mg Q4W (N = 1), -9.6 (3.7) in the dupilumab 300 mg Q4W (N = 2), -1.6 (0.6) in the dupilumab 300 mg Q4W, 600 mg LD (N = 2), and -3.4 (3.2) in the dupilumab 200 mg Q4W, 400 mg LD (N = 5). A numerical improvement in HSS7 was observed at Week 24 regardless of dosing regimen, with a mean (SD) change from baseline of -3.0 in the dupilumab 200 mg Q4W (N = 1), -11.8 (1.8) in the dupilumab 300 mg Q4W (N = 2), -1.2 (1.2) in the dupilumab 300 mg Q4W, 600 mg LD (N = 2), and -4.4 (3.6) in the dupilumab 200 mg Q4W, 400 mg LD (N = 5).

Fifteen participants were enrolled and exposed. Following repeated administration of dupilumab, the mean Ctrough of functional dupilumab in pediatric participants >=2 years to <12 years of age with uncontrolled CSU in general increased quickly after the first dose, was maintained during the treatment period and decreased after cessation of treatment. Dupilumab was safe and well-tolerated with no new safety signals identified. None of the participants had positive ADA response.

Yes

Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://vivli.org

https://jrct.mhlw.go.jp/latest-detail/jRCT2031220733

Obara Kentaro

Sanofi K.K.

Tokyo Opera City Tower, 3-20-2, Nishi Shinjuku, Shinjuku-ku, Tokyo 163-1488, Japan

clinical-trials-jp@sanofi.com

Clinical Study Unit

Sanofi K.K.

Tokyo Opera City Tower, 3-20-2, Nishi Shinjuku, Shinjuku-ku, Tokyo 163-1488, Japan

+81-3-6301-3670

clinical-trials-jp@sanofi.com

Complete

Mar. 30, 2023

Interventional

randomized controlled trial

open(masking not used)

uncontrolled control

single assignment

treatment purpose

- Participant must be >= 2 years to < 12 years of age, at the time of signing the informed consent.
- Participants who have history of a diagnosis of CSU prior to screening (Visit 1) or symptoms consistent with a diagnosis of CSU for at least 3 months in the Investigator's opinion.
- Participants with CSU (characterized by recurrent itchy wheals with or without angioedema for >6 consecutive weeks) who remain symptomatic at the time of screening despite regular H1-antihistamine treatment.
- Body weight within >=5 kg to <60 kg.
- Participant/parent(s)/caregiver(s)/participant's legally authorized representative, as appropriate, willing and able to comply with study visits and related procedures.

Participants are excluded from the study if any of the following criteria apply:
Medical conditions
- Underlying etiology for chronic urticarias other than CSU.
- Presence of skin morbidities other than CSU that may interfere with the assessment of the study outcomes.
- Participants with a diagnosis of chronic inducible cold urticaria.
- Participants with active AD.
- Severe concomitant illness(es) that, in the Investigator's judgment, would adversely affect the patient's participation in the study.
- Participants with active tuberculosis (TB) or non-tuberculous mycobacterial infection, or a history of incompletely treated.
- Diagnosed with, suspected of, or at high risk of endoparasitic infection.
- Active chronic or acute infection requiring treatment with systemic antibiotics, antivirals, or antifungals within 2 weeks before the screening visit or during the screening period.
- Known or suspected immunodeficiency.
- Active malignancy or history of malignancy within 5 years before the baseline visit.
- History of systemic hypersensitivity or anaphylaxis to dupilumab including any excipient.
- Participation in prior dupilumab clinical study or have been treated with commercially available dupilumab.

Both

Chronic Spontaneous Urticaria

Drug: Dupilumab
Pharmaceutical form: Injection solution Subcutaneous
Other Name: Dupixent

1.Concentration of dupilumab in serum over time including Ctrough at Week 12 and Week 24
[Time Frame baseline:Week 12 and Week 24]

1. Incidence of treatment-emergent adverse events (TEAEs) or serious adverse events (SAEs)
[Time Frame baseline:Baseline to Week 36]
2. Incidence of anti-drug antibodies (ADA) to dupilumab over time
[Time Frame baseline:Baseline to Week 36]
3. Change from baseline in Children's Dermatology Quality Life Index (C-DLQI) in children from 4 years to less than 12 years of age at Week 24
[Time Frame baseline:Baseline to Week 24]
The C-DLQI is a validated questionnaire designed to measure the impact of skin disease on children's Health-Related Quality of Life (HRQoL). The questionnaire is validated for children aged >=4 to <16 years. The C-DLQI total score ranges 0 to 30. The higher the score, the greater the impact is on the child's HRQoL.
4. Change from baseline in Infants' Dermatitis Quality of Life Index (IDQOL) in children from 2 years to less than 4 years of age at Week 24
[Time Frame baseline:Baseline to Week 24]
The IDQOL is a validated questionnaire designed for use in children aged <4 years. The IDLQI total score ranges 0 to 30. The higher the score, the greater the impact is on the child's HRQoL.
5. Change from baseline in the modified Urticaria Activity Score (UAS7) at Week 24
[Time Frame baseline:Baseline to Week 24]
The UAS is a validated patient reported outcome (PRO) measure. A modified version of the UAS (mUAS) will be used in this study to account for the smaller body surface area of child and adolescent patients. Daily mUAS scores are summed over 7-day period to create the mUAS7, ranging from 0 to 42. The higher score indicates the greater urticaria activity.
6. Change from baseline in the modified itch severity score over 7 days (ISS7) at Week 24
[Time Frame baseline:Baseline to Week 24]
ISS7 ranges from 0 (absent) to 3 (intense). Daily Itch Severity Score (ISS) scores are summed over 7-day period to create the ISS7, ranging from 0 to 21.
7. Change from baseline in the modified Hive Severity Score over 7 days (HSS7) at Week 24
[Time Frame baseline:Baseline to Week 24]
HSS7 ranges from 0 (absent) to 3 (intense), (>30 wheals/24 hours or large confluent areas of wheals). Daily HSS scores are summed over 7-day period to create the HSS7, ranging from 0 to 21.

Feb. 28, 2023

Canada/United States