A study to evaluate the efficacy and safety of subcutaneous amlitelimab monotherapy compared with placebo in participants aged 18 years and older with moderate-to-severe atopic dermatitis

JRCT ID: jRCT2061230089

Registered date:13/01/2024

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: Dermatitis atopic
• Date of first enrollment: 22/01/2024
• Target sample size: 420
• Countries of recruitment: TBD,Japan
• Study type: Interventional

Intervention(s)

Drug: SAR445229 (amlitelimab)
Pharmaceutical form: Injection solution, Route of administration: Subctaneous injection
Drug: Placebo
Pharmaceutical form: Injection solution, Route of administration: Subctaneous injection

Arm description
- Experimental: Amlitelimab dose 1, Subcutaneous injection as per protocol
- Experimental: Amlitelimab dose 2, Subcutaneous injection as per protocol
- Placebo Comparator: Placebo, Subcutaneous injection as per protocol

Outcome(s)

Primary Outcome

1. European Union (EU), EU reference countries, and Japan: Proportion of participants with Validated Investigator Global Assessment scale for Atopic Dermatitis (vIGA-AD) of 0 (clear) or 1 (almost clear) and a reduction from baseline of >=2 points at Week 24
[Time Frame: Week 24]
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).
2. EU, EU reference countries, and Japan: Proportion of participants reaching 75% reduction from baseline in Eczema Area and Severity Index (EASI) score (EASI-75) at Week 24
[Time Frame: Week 24]
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.
3. United States (US) and US reference countries: Proportion of participants with vIGA-AD of 0 (clear) or 1 (almost clear) and a reduction from baseline of >=2 points at Week 24
[Time Frame: Week 24]
Refer to the primary outcome-1 for "vIGA-AD".

Secondary Outcome

1. Proportion of participants reaching EASI-75 at Week 24 (for US and US reference countries only)
[Time Frame: Week 24]
Refer to the primary outcome-2 for "EASI". EASI-75 is 75% reduction from baseline in EASI score.
2. Proportion of participants with vIGA-AD 0 (clear) or 1 (almost clear) with presence of only barely perceptible erythema (no induration/papulation, no lichenification, no oozing or crusting)
[Time Frame: Baseline to Week 24]
Refer to the primary outcome-1 for "vIGA-AD".
3. Proportion of participants with >=4-point reduction in weekly average of daily Peak Pruritus-Numerical Rating Scale (PP-NRS) from baseline in participants with baseline weekly average of daily PP-NRS >=4
[Time Frame: Baseline to Week 24]
The PP-NRS is a validated single item 0-10 numeric rating scale assessing peak pruritus (itch) associated with AD with 0 = no itch and 10 = worst itch imaginable.
4. Proportion of participants reaching EASI-75
[Time Frame: Baseline to Week 20]
Refer to the primary outcome-2 for "EASI". EASI-75 is 75% reduction from baseline in EASI score.
5. Proportion of participants with vIGA-AD of 0 (clear) or 1 (almost clear) and a reduction from baseline of >=2 points
[Time Frame: Baseline to Week 20]
Refer to the primary outcome-1 for "vIGA-AD".
6. Proportion of participants reaching EASI-90
[Time Frame: Baseline to Week 24]
Refer to the primary outcome-2 for "EASI". EASI-90 is 90% reduction from baseline in EASI score.
7. Proportion of participants reaching EASI-100
[Time Frame: Baseline to Week 24]
Refer to the primary outcome-2 for "EASI". EASI-100 is 100% reduction from baseline in EASI score.
8. Change in Dermatology Quality of Life (QoL) Index (DLQI) from baseline
[Time Frame: Baseline to Week 24]
The DLQI is a validated 10-item questionnaire to measure dermatology-specific QoL in adult patients. Overall scoring ranges from 0 to 30, with a higher score indicating a poorer QoL.
9. Proportion of participants with a reduction in DLQI >=4 from baseline in participants with DLQI baseline >=4
[Time Frame: Baseline to Week 24]
Refer to the secondary outcome-8 for "DLQI".
10. Change in Hospital Anxiety Depression Scale (HADS) from baseline
[Time Frame: Baseline to Week 24]
The HADS is 14-item questionnaire with two subscales: anxiety & depression. Each subscale (anxiety & depression) ranges 0-21. The total HADS score ranges 0-42 with higher score indicating a poorer state.
11. Proportion of participants with HADS subscale Anxiety (HADS-A) <8 in participants with baseline HADS-A >=8
[Time Frame: Baseline to Week 24]
HADS-A score ranges 0-21 with higher score indicating a poorer state.
12. Proportion of participants with HADS subscale Depression (HADS-D) <8 in participants with HADS-D baseline >=8
[Time Frame: Baseline to Week 24]
HADS-D score ranges 0-21 with higher score indicating a poorer state.
13. Change in weekly average of daily Skin Pain-Numerical Rating Scale (SP-NRS) from baseline
[Time Frame: Baseline to Week 24]
The SP-NRS is a single item 0-10 numeric rating scale assessing skin pain associated with AD with 0 = no pain and 10 = worst possible pain imaginable.
14. Proportion of participants with a reduction in weekly average of daily SP-NRS >=4 from baseline in participants with baseline weekly average of daily SP-NRS >=4
[Time Frame: Baseline to Week 24]
Refer to the secondary outcome-13 for "SP-NRS".
15. Change in weekly average of daily Sleep Disturbance-Numerical Rating Scale (SD-NRS) from baseline
[Time Frame: Baseline to Week 24]
The SD-NRS is a single item 0-10 numeric rating scale assessing sleep disturbance associated with AD with 0 = no sleep loss and 10 = did not sleep at all.
16. Proportion of participants with a reduction in weekly average of daily SD-NRS >=3 from baseline in participants with Baseline weekly average of daily SD-NRS >=3
[Time Frame: Baseline to Week 24]
Refer to the secondary outcome-15 for "SD-NRS".
17. Proportion of participants with a reduction in weekly average of daily SD-NRS >=5 from baseline in participants with baseline weekly average of daily SD-NRS >=5
[Time Frame: Baseline to Week 24]
Refer to the secondary outcome-15 for "SD-NRS".
18. Percent change in EASI score from baseline
[Time Frame: Baseline to Week 24]
Refer to the primary outcome-2 for "EASI".
19. Percent change in weekly average of daily PP-NRS from baseline
[Time Frame: Baseline to Week 24]
Refer to the secondary outcome-3 for "PP-NRS".
20. Proportion of participants reaching EASI-50
[Time Frame: Baseline to Week 24]
Refer to the primary outcome-2 for "EASI". EASI-50 is 50% reduction from baseline in EASI score.
21. Proportion of participants with EASI =<7
[Time Frame: Baseline to Week 24]
Refer to the primary outcome-2 for "EASI".
22. Change in percent Body Surface Area (BSA) affected by AD from baseline
[Time Frame: Baseline to Week 24]
23. Percent change in Scoring Atopic Dermatitis (SCORAD) index from baseline
[Time Frame: Baseline to Week 24]
The SCORAD index is a clinical tool to evaluate the extent and severity of AD. Total score ranges from 0 (absent disease) to 103 (severe disease).
24. Proportion of participants with a reduction in SCORAD >=8.7 points from baseline in participants with baseline SCORAD score >=8.7
[Time Frame: Baseline to Week 24]
Refer to the secondary outcome-23 for "SCORAD".
25. Proportion of participants with a reduction in Patient Oriented Eczema Measure (POEM) >=4 from baseline in participants with POEM Baseline >=4
[Time Frame: Baseline to Week 24]
The POEM is a 7-item self-assessment questionnaire that assesses disease symptoms on a 5-point scale; 0 (no days) to 4 (every day in the last week). The sum of the 7 items gives the total POEM score of 0 (absent disease) to 28 (very severe). Higher scores indicated more severe disease and poor quality of life.
26. Change in POEM from baseline
[Time Frame: Baseline to Week 24]
Refer to the secondary outcome-25 for "POEM".
27. Proportion of participants with rescue medication use [from baseline to Week 24]
[Time Frame: Baseline to Week 24]
28. Percentage of participants who experienced Treatment-Emergent Adverse Events, experienced Treatment-Emergent Serious Adverse Events and/or Treatment-Emergent Adverse Events of Special Interest
[Time Frame: Baseline to Week 40]
29. Serum amlitelimab concentrations
[Time Frame: Baseline to Week 40]
30. Incidence of antidrug antibodies of amlitelimab
[Time Frame: Baseline to Week 40]

Key inclusion & exclusion criteria

• Age minimum: >= 18age old
• Age maximum: Not applicable
• Gender: Both

Include criteria

- Participants must be 18 years of age (when signing informed consent form)
- Diagnosis of atopic dermatitis (AD) for at least 1 year (defined by the American Academy of Dermatology Consensus Criteria)
- Documented history (within 6 months before screening) of either inadequate response or inadvisability to topical treatments, and/or inadequate response to systemic therapies (within 12 months before screening)
- Validated Investigatr Global Assessment scale for Atopic Dermatitis (vIGA-AD) of 3 or 4 at baseline visit
- Eczema Area and Severity Index (EASI) score of 16 or higher at baseline
- AD involvement of 10% or more of Body Surface Area (BSA) at baseline
- Weekly average of daily Peak Pruritus-Numerical Rating Scale (PP-NRS) of >=4 at baseline visit
- Able and willing to comply with requested study visits and procedures
- Body weight >=40 kg

Exclude criteria

Participants are excluded from the study if any of the following criteria apply:
- Skin co-morbidity that would adversely affect the ability to undertake AD assessments
- Known history of or suspected significant current immunosuppression
- Any malignancies or history of malignancies prior to baseline (excluding for non-melanoma skin cancer excised and cured >5 years prior to baseline)
- History of solid organ or stem cell transplant
- Any active or chronic infection including helminthic infection requiring systemic treatment within 4 weeks prior baseline
- Positive for human immunodeficiency virus, hepatitis B or hepatitis C at screening visit
- Having active tuberculosis (TB), latent TB, a history of incompletely treated TB, suspected extrapulmonary TB infection, or who are at high risk of contracting TB
- Having received any of the specified therapy within the specified timeframe(s) prior to the baseline visit
- In the Investigator's opinion, any clinically significant laboratory results or protocol specified laboratory abnormalities at screening
- History of hypersensitivity or allergy to any of the excipients or investigational medicinal product

Related Information

• Primary Sponsor: Tanaka Tomoyuki
• Secondary ID(s): NCT06181435,2023-506557-38