A Phase 3, randomized, double-blind, placebo-controlled, parallel-group, 3-arm, multinational, multicenter study to evaluate the efficacy and safety of amlitelimab by subcutaneous injection in participants aged 12 years and older with moderate-to-severe atopic dermatitis (AD) who are on background topical corticosteroids and have had an inadequate response to prior biologic therapy or oral Janus Kinase (JAK) inhibitor treatment
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 (AQUA)
Tanaka Tomoyuki
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
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
Recruiting
May. 23, 2024
249
Interventional
randomized controlled trial
double blind
placebo control
parallel assignment
treatment purpose
- 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
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.
12age old over
No limit
Both
Dermatitis atopic
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
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".
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".
Sanofi K.K.
Byouin Godou Institutional Review Board
Sanyou Kochi Building 3F, 1-14 Minami-kubo, Kochi-shi, Kochi, Kochi
+81-88-861-2111
godou-irb@eps.co.jp
Approval
April. 19, 2024
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
