A study to evaluate the treatment response and safety of two dose regimens of subcutaneous amlitelimab monotherapy compared with treatment withdrawal in participants aged 12 years and older with moderate-to-severe atopic dermatitis

JRCT ID: jRCT2061240027

Registered date:28/06/2024

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: Dermatitis atopic
• Date of first enrollment: 22/07/2024
• Target sample size: 961
• Countries of recruitment: United States,Japan
• Study type: Interventional

Intervention(s)

Drug: Amlitelimab (SAR445229)
Pharmaceutical form: Injection solution
Route of administration: Subcutaneous (SC) injection
Drug: Placebo
Pharmaceutical form: Injection solution
Route of administration: SC injection

Study Arms:
Experimental: Amlitelimab dose 1
SC injection as per protocol
Drug: Amlitelimab
Experimental: Amlitelimab dose 2
SC injection as per protocol
Drug: Amlitelimab
Placebo Comparator: Placebo
SC injection as per protocol
Drug: Placebo

Outcome(s)

Primary Outcome

Proportion of participants who maintain clinical response at Week (W) 48 of ESTUARY.
[Time frame: W48]
Maintenance of clinical response is defined as having validated Investigator Global Assessment scale for atopic dermatitis (vIGA-AD) 0 (clear) or 1 (almost clear) and/or 75% reduction in Eczema Area and Severity Index (EASI) compared to parent study baseline EASI (EASI-75). The vIGA-AD is an Investigator-completed assessment scale used to determine severity of AD and clinical response to treatment. It is based on a 5-point scale, ranging from 0 (clear) to 4 (severe). The EASI is an Investigator-assessed validated tool used to measure the extent (area) and severity of AD. Total score ranges from 0 to 72 with a higher score indicating increased extent and severity of AD.

Secondary Outcome

Responders from parent studies:
- Proportion of participants who continue to be EASI-75 among the participants who met EASI-75 at baseline of ESTUARY [Up to W48]
- Proportion of participants who continue to be vIGA-AD 0 or 1 among participants who met vIGA-AD 0 or 1 at baseline of ESTUARY [Up to W48]
- Proportion of participants who continue to be vIGA-AD 0 or 1 with presence of only barely perceptible erythema (no induration/papulation, no lichenification, no oozing or crusting) among the participants who are vIGA-AD 0 or 1 with presence of only barely perceptible erythema at baseline of ESTUARY [Up to W48]
- Proportion of participants who maintained weekly average of daily Peak Pruritus-Numerical Rating Scale (PP-NRS) reduction of >=4 among the participants with weekly average of daily PP-NRS reduction of >=4 at baseline of ESTUARY [Up to W48]
- Percent change in EASI from parent study baseline [Up to W48]
- Proportion of participants with EASI-75/50/90/100 [Up to W48]
- Proportion of participants who continue to be EASI-50/90/100 among the participants who met EASI-50/90/100 at baseline of ESTUARY [Up to W48]
- Time to the first event of loss of EASI-75/50/90/100 response among the participants who were EASI-75/50/90/100 responders at baseline of ESTUARY [Up to W48]
- Proportion of participants with vIGA-AD 0 or 1 [Up to W48]
- Proportion of participants who are vIGA-AD 0 or 1 with presence of only barely perceptible erythema [Up to W48]
- Time to first event of vIGA-AD >=3 (moderate or severe) among those participants who were vIGA-AD 0 or 1/0 at baseline of ESTUARY [Up to W48]
- Proportion of participants who have an increase of >=2 points in vIGA-AD from ESTUARY baseline among the participants who were vIGA-AD 0 or 1/3/4 at baseline of ESTUARY [Up to W48]
- Proportion of participants with vIGA-AD 0 or 1 and/or EASI-75 among the participants who were vIGA-AD 0 or 1 and/or EASI-75 at baseline of ESTUARY [Up to W48]
- Proportion of participants with >=4 points reduction in weekly average of daily PP-NRS from parent study baseline [Up to W48]
- Percent/Absolute change in weekly average of daily PP-NRS from parent study baseline [Up to W48]
- Proportion of participants who maintained PP-NRS 0 or 1 among the participants who were PP-NRS 0 or 1 at baseline of ESTUARY [Up to W48]
- Proportion of participants who maintained vIGA-AD 0 or 1 and/or EASI-75 and weekly average of daily PP-NRS reduction >=4 among the participants who were vIGA-AD 0 or 1 and/or EASI-75 and weekly average of daily PP-NRS reduction >=4 at baseline of ESTUARY [Up to W48]
- Absolute change in weekly average of daily Sleep Disturbance-Numerical Rating Scale (SD-NRS) from parent study baseline [UP to W48]
- Proportion of participants who maintained weekly average of daily SD-NRS reduction of >=3 among the participants with weekly average of daily SD-NRS reduction of >=3 at baseline of ESTUARY [Up to W48]
- Proportion of participants with >=3 points reduction in weekly average of daily SD-NRS from parent study baseline [Up to W48]
- Proportion of participants with >= 4 points reduction in weekly average of daily Skin Pain-Numerical Rating Scale (SP-NRS) from parent study baseline [Up to W48]
- Proportion of participants who maintained weekly average of daily SP-NRS reduction of >=4 among the participants with weekly average of daily SP-NRS reduction of >=4 at ESTUARY baseline [Up to W48]
- Absolute change in weekly average of daily SP-NRS from parent study baseline [Up to W48]
- Proportion of participants who maintained Scoring of Atopic Dermatitis (SCORAD) >=8.7 among participants with reduction in SCORAD >=8.7 at baseline of ESTUARY [Up to W48]
- Percent/Absolute change in SCORAD index from parent study baseline [Up to W48]
- Change in percent Body Surface Area affected by AD from parent study baseline [Up to W48]
- Proportion of participants who maintained Patient Oriented Eczema Measure (POEM) >=4 among the participants with reduction in POEM >=4 at baseline of ESTUARY [Up to W48]
- Change in POEM from parent study baseline [UP to W48]
- Proportion of participants with a reduction in Children's Dermatology Quality of Life (QOL) Index (CDLQI) >=6 among participants aged >=12 to <16 years old and with CDLQI baseline >=6 [Up to W48]
- Change in CDLQI in participants with age >=12 to <16 years old [Up to W48]
- Change in Dermatology Life Quality Index (DLQI) in participants with age >=16 years among the participants with DLQI >=4 at parent study baseline [Up to W48]
- Proportion of participants with >=4 points reduction in DLQI from parent study baseline among the participants with DLQI >=4 at parent study baseline [Up to W48]
- Proportion of participants with Hospital Anxiety and Depression Scale (HADS)-Depression (HADS-D) <8 among the participants who had HADS-D >=8 at parent study baseline [Up to W48]
- Proportion of participants with HADS-Anxiety (HADS-A) <8 among the participants who had HADS-A >=8 at parent study baseline [Up to W48]
- Proportion of participants requiring rescue medication during the study up to W48 of ESTUARY [Up to W48]
- Time to first rescue medication initiation [Up to W48]

Non-responders from parent studies:
- Percent change in EASI from parent study baseline [Up to W48]
- Proportion of participants with EASI-75 [Up to W48]
- Proportion of participants who continue to be EASI-50 among the participants who met EASI-50 at baseline of ESTUARY [Up to W48]
- Proportion of participants with EASI-50/90/100 [Up to W48]
- Proportion of participants with vIGA-AD 0 or 1 [Up to W48]
- Proportion of participants who are vIGA-AD 0 or 1 with presence of only barely perceptible erythema [Up to W48]
- Proportion of participants with >=4 points reduction in weekly average of daily PP-NRS from parent study baseline [Up to W48]
- Percent/Absolute change in weekly average of daily PP-NRS from parent study baseline [Up to W48]
- Absolute change in weekly average of daily SD-NRS from parent study baseline [Up to W48]
- Proportion of participants with >=3 points reduction in weekly average of daily SD-NRS from parent study baseline [Up to W48]
- Proportion of participants with >=4 points reduction in weekly average of daily SP-NRS from parent study baseline [Up to W48]
- Absolute change in weekly average of daily SP-NRS from parent study baseline [Up to W48]
- Proportion of participants with a reduction in CDLQI >=6 among participants aged >=12 to <16 years old and with CDLQI >=6 at parent study baseline [Up to W48]
- Change in CDLQI in participants with age >=12 to <16 years old [Up to W48]
- Change in DLQI in participants with age >=16 years among the participants with DLQI >=4 at parent study baseline [Up to W48]
- Proportion of participants with >=4 points reduction in DLQI from parent study baseline among the participants with DLQI >=4 at parent study baseline [Up to W48]
- Proportion of participants with HADS-D <8 among the participants who had HADS-D >=8 at parent study baseline [Up to W48]
- Proportion of participants with HADS-A <8 among the participants who had HADS-A >=8 at parent study baseline [Up to W48]

All participants:
- Percentage of participants who experienced Treatment-Emergent Adverse Events (TEAEs), Treatment-Emergent Serious Adverse Events (TESAEs) and/or Treatment-Emergent Adverse Events of Special Interest (AESI) [Up to W64]
- Serum amlitelimab concentrations measured at prespecified timepoints [Up to W64]
- Incidence of antidrug antibodies (ADAs) of amlitelimab [Up to W64]

Key inclusion & exclusion criteria

• Age minimum: >= 12age old
• Age maximum: Not applicable
• Gender: Both

Include criteria

- Participants must be at least 12 years of age inclusive, at the time the informed consent form (ICF) is signed.
- Must have participated, received study treatment without permanent investigational medicinal product discontinuation, and adequately completed the assessments required for the treatment period in one of the three 24-week parent studies EFC17559 (COAST-1), EFC17560 (COAST-2) or EFC17561 (SHORE) for moderate-to-severe atopic dermatitis (AD).
- Able and willing to comply with requested study visit and procedures.
- Body weight must be >=25 kg.

Exclude criteria

Participants are excluded from the study if any of the following criteria apply:
- Developed a medical condition that would preclude participation as described in Permanent Discontinuation of EFC17559 (COAST-1)/EFC17560 (COAST-2)/EFC17561 (SHORE) clinical trial protocols.
- Having received any prohibited medication or procedure for AD that resulted in investigational medicinal product discontinuation in the parent study EFC17559 (COAST-1), EFC17560 (COAST-2) or EFC17561 (SHORE).
- Participants who, during their participation in the parent study EFC17559 (COAST-1)/EFC17560 (COAST-2)/EFC17561 (SHORE), developed an adverse event (AE) or a serious adverse event (SAE) deemed related to amlitelimab, which in the opinion of the Investigator could indicate that continued treatment with amlitelimab may present an unreasonable risk for the participant.
- Participants who have had investigational medicinal product permanently discontinued for any reason before or at the time of the planned first dose in the EFC17600 (ESTUARY) study.
- Conditions in the parent study EFC17559 (COAST-1)/EFC17560 (COAST-2)/EFC17561 (SHORE) that led to Investigator - or Sponsor-initiated withdrawal of participant from the study (eg, non-compliance, inability to complete study assessments, etc.).
- Participant not suitable for participation, whatever the reason, as judged by the Investigator, including medical or clinical conditions, or participants potentially at risk of noncompliance to study procedures.

Related Information

• Primary Sponsor: Tanaka Tomoyuki
• Secondary ID(s): NCT06407934,2023-508096-36