A study to evaluate the efficacy and safety of subcutaneous amlitelimab on background topical corticosteroids therapy in participants aged 12 years and older with moderate-to-severe AD who have had an inadequate response to prior biologic therapy or an oral JAK inhibitor

JRCT ID: jRCT2061240007

Registered date:08/05/2024

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: Dermatitis atopic
• Date of first enrollment: 23/05/2024
• Target sample size: 249
• Countries of recruitment: Canada,Japan,Chile,Japan,United Kingdom,Japan,United States,Japan
• Study type: Interventional

Intervention(s)

Drug: Amlitelimab (SAR445229)
Pharmaceutical form: Injection solution, Route of administration: Subcutaneous
Drug: Placebo
Pharmaceutical form: Injection solution, Route of administration: Subcutaneous
Drug: Topical corticosteroids
Pharmaceutical form: Various Topical formulation, Route of administration: Topical
Drug: Topical tacrolimus or pimecrolimus
Pharmaceutical form: Various Topical formulation, Route of administration: Topical

Study Arms
- Experimental: Amlitelimab dose 1
Subcutaneous injection as per protocol
Drug: Amlitelimab, Topical corticosteroids, Topical tacrolimus or pimecrolimus
- Experimental: Amlitelimab dose 2
Subcutaneous injection as per protocol
Drug: Amlitelimab, Topical corticosteroids, Topical tacrolimus or pimecrolimus
- Placebo Comparator: Placebo
Subcutaneous injection as per protocol
Drug: Placebo, Topical corticosteroids, Topical tacrolimus or pimecrolimus

Outcome(s)

Primary Outcome

1. European Union (EU), EU reference countries, and Japan: Proportion of participants with vIGA-AD of 0 (clear) or 1 (almost clear) and a reduction from baseline of >= 2 points at Week 36
[Time Frame: Week 36]
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 EASI score (EASI-75) at Week 36
[Time Frame: Week 36]
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 36
[Time Frame: Week 36]
Refer to the primary outcome-1 for "vIGA-AD".

Secondary Outcome

1. Proportion of participants reaching EASI-75 at Week 36 (for US and US reference countries only)
[Time Frame: Week (W) 36]
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 (Base) to W36]
Refer to the primary outcome-1 for "vIGA-AD".
3. Proportion of participants with >= 4-point reduction in weekly average of daily PP-NRS from baseline in participants with baseline weekly average of daily PP-NRS >= 4
[Time Frame: Base to W36]
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: Base to W24]
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: Base to W24]
Refer to the primary outcome-1 for "vIGA-AD".
6. Proportion of participants reaching EASI-90
[Time Frame: Base to W36]
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: Base to W36]
Refer to the primary outcome-2 for "EASI". EASI-100 is 100% reduction from baseline in EASI score.
8. Proportion of participants with PP-NRS 0 or 1
[Time Frame: Base to W36]
Refer to the secondary outcome-3 for "PP-NRS".
9. Change in Dermatology Quality of Life Index (DLQI) from baseline in participants with age >= 16 years old
[Time Frame: Base to W36]
The DLQI is a validated 10-item questionnaire to measure dermatology-specific quality of life (QoL) in adult patients. Overall scoring ranges from 0 to 30, with a higher score indicating a poorer QoL.
10. Proportion of participants with a reduction in DLQI >= 4 from baseline in participants with age >= 16 years old and with DLQI baseline >= 4
[Time Frame: Base to W36]
Refer to the secondary outcome-9 for "DLQI".
11. Change in Children Dermatology Quality of Life Index (CDLQI) from baseline in participants with age >= 12 to < 16 years
[Time Frame: Base to W36]
The CDLQI is a validated 10-item questionnaire to measure dermatology-specific QoL in children aged 4- < 16 years. Overall scoring ranges from 0 to 30, with a higher score indicating a poorer QoL.
12. Proportion of participants with a reduction in CDLQI >= 6 from baseline in participants with age >= 12 to < 16 years old and with CDLQI baseline >=6
[Time Frame: Base to W36]
Refer to the secondary outcome-11 for "CDLQI".
13. Change in Hospital Anxiety Depression Scale (HADS) from baseline
[Time Frame: Base to W36]
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.
14. Proportion of participants with HADS subscale Anxiety (HADS-A) < 8 in participants with baseline HADS-A >= 8
[Time Frame: Base to W36]
HADS-A score ranges 0-21 with higher score indicating a poorer state.
15. Proportion of participants with HADS subscale Depression (HADS-D) < 8 in participants with HADS-D baseline >= 8
[Time Frame: Base to W36]
HADS-D score ranges 0-21 with higher score indicating a poorer state.
16. Absolute change in weekly average of daily Skin Pain-Numerical Rating Scale (SP-NRS) from baseline
[Time Frame: Base to W36]
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.
17. 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: Base to W36]
Refer to the secondary outcome-16 for "SP-NRS".
18. Absolute change in weekly average of daily Sleep Disturbance-Numerical Rating Scale (SD-NRS) from baseline
[Time Frame: Base to W36]
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.
19. Percent change in EASI score from baseline
[Time Frame: Base to W36]
Refer to the primary outcome-2 for "EASI".
20. Percent change in weekly average of daily PP-NRS from baseline
[Time Frame: Base to W36]
Refer to the secondary outcome-3 for "PP-NRS".
21. Absolute change in weekly average of daily PP-NRS from baseline
[Time Frame: Base to W36]
Refer to the secondary outcome-3 for "PP-NRS".
22. Proportion of participants reaching EASI-50
[Time Frame: Base to W36]
Refer to the primary outcome-2 for "EASI". EASI-50 is 50% reduction from baseline in EASI score.
23. Proportion of participants with EASI <= 7
[Time Frame: Base to W36]
Refer to the primary outcome-2 for "EASI".
24. Change in percent BSA affected by AD from baseline
[Time Frame: Base to W36]
25. Percent change in Scoring Atopic Dermatitis (SCORAD) index from baseline
[Time Frame: Base to W36]
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).
26. Absolute change in SCORAD index from baseline
[Time Frame: Base to W36]
Refer to the secondary outcome-25 for "SCORAD".
27. Proportion of participants with a reduction in SCORAD >= 8.7 points from baseline in participants with baseline SCORAD score >= 8.7
[Time Frame: Base to W36]
Refer to the secondary outcome-25 for "SCORAD".
28. Proportion of participants with a reduction in Patient Oriented Eczema Measure (POEM) >= 4 from baseline in participants with POEM Baseline >= 4
[Time Frame: Base to W36]
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.
29. Change in POEM from baseline
[Time Frame: Base to W36]
Refer to the secondary outcome-28 for "POEM".
30. Proportion of participants with rescue medication use
[Time Frame: Base to W36]
31. Time to onset of effect on PP-NRS as measured by proportion of participants with an improvement (reduction) in PP-NRS by >= 4
[Time Frame: Base to W36]
Refer to the secondary outcome-3 for "PP-NRS".
32. Percentage of topical corticosteroid (TCS) / topical calcineurin inhibitor (TCI) free days
[Time Frame: Base to W36]
33. Percentage of participants who experience Treatment-Emergent Adverse Events (TEAEs), experience Treatment-Emergent Serious Adverse Events (TESAEs) and/or Treatment-Emergent Adverse Events of Special Interest (AESI)
[Time Frame: Base to W52]
34. Serum amlitelimab concentrations
[Time Frame: Base to W52]
35. Incidence of antidrug antibodies (ADAs) of amlitelimab
[Time Frame: Base to W52]
36. Time to onset of effect on vIGA-AD as measured by proportion of participants with vIGA-AD 0 (clear) or 1 (almost clear) and a reduction from baseline >= 2 during the 36-week treatment period
[Time Frame: Base to W36]
Refer to the primary outcome-1 for "vIGA-AD".
37. Time to onset of effect on EASI as measured by proportion of participants reaching a 75% reduction from baseline in EASI score during the 36-week treatment period
[Time Frame: Base to W36]
Refer to the primary outcome-2 for "EASI".

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 (when signing informed consent form).
- Diagnosis of AD for at least 1 year (defined by the American Academy of Dermatology Consensus Criteria).
- Documented history prior to screening visit of inadequate response to a biologic AD medication or an oral JAK inhibitor (JAKi) therapy.
- Validated Investigator Global Assessment 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 >= 25 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 (with the exception of 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 to 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): NCT06241118,2023-508099-12