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

Dermatitis Atopic Clinical Trial

— AQUA  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06241118
• Other study ID #: EFC17599
• Secondary ID: 2023-508099-12U1
• Status: Recruiting
• Phase: Phase 3
• Start date: February 29, 2024
• Est. completion date: June 30, 2026

Study information

• Verified date: June 2024
• Source: Sanofi
• Contact: Trial Transparency email recommended (Toll free for US & Canada)
• Phone: 800-633-1610
• Email: Contact-US[@]sanofi.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a parallel group, Phase 3, multinational, multicenter, randomized, double-blind, placebo-controlled, 3-arm study for treatment of participants diagnosed with moderate-to-severe AD on background TCS who have had inadequate response to prior biologic or oral JAKi therapy.

The purpose of this study is to measure the efficacy and safety of treatment with amlitelimab solution for subcutaneous (SC) injection compared with placebo in participants with moderate-to-severe AD aged 12 years and older on background TCS and have had an inadequate response to prior biologic or an oral JAKi therapy.

Study details include:

At the end of the treatment period, participants will have the option to enter the Long-Term Safety Study LTS17367 (RIVER-AD).

The study duration will be up to 56 weeks for participants not entering the long-term safety study (LTS17367 [RIVER-AD]) including a 2 to 4-week screening, a 36-week randomized double-blind period, and a 16-week safety follow-up.

The study duration will be up to 40 weeks for participants entering the long-term safety study (LTS17367 [RIVER-AD]) including a 2 to 4-week screening and a 36-week randomized double-blind period.

The total treatment duration will be up to 36 weeks. The total number of visits will be up to 13 visits (or 12 visits for those entering the long-term safety study LTS17367 [RIVER-AD] study).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 249
• Est. completion date: June 30, 2026
• Est. primary completion date: March 20, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Years and older

Eligibility

Inclusion Criteria:

• Participants must be 12 years of age (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 JAKi therapy.

• v-IGA-AD of 3 or 4 at baseline visit

• EASI score of 16 or higher at baseline

• AD involvement of 10% or more of BSA at baseline

• Weekly average of daily PP-NRS of = 4 at baseline visit.

• Able and willing to comply with requested study visits and procedures

• Body weight =25 kg

Exclusion 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 (HIV), 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 (IMP)

The above information is not intended to contain all considerations relevant to a potential participation in a clinical trial

Related Conditions & MeSH terms

• Dermatitis
• Dermatitis Atopic
• Dermatitis, Atopic

Intervention

Drug:
• Amlitelimab
Pharmaceutical form: Injection solution Route of administration: Subcutaneous
• Placebo
Pharmaceutical form: Injection solution Route of administration: Subcutaneous
• Topical corticosteroids
Pharmaceutical form: Various Topical formulation Route of administration: Topical
• Topical tacrolimus or pimecrolimus
Pharmaceutical form: Various Topical formulation Route of administration: Topical

Locations

Country	Name	City	State
Argentina	Investigational Site Number : 0320011	Caba	Buenos Aires
Argentina	Investigational Site Number : 0320019	Caba	Buenos Aires
Argentina	Investigational Site Number : 0320007	Rosario	Santa Fe
Brazil	FUNDACAO DO ABC - FACULDADE DE MEDICINA DO ABC (FMABC) Site Number : 0760001	Santo Andre	São Paulo
Canada	Investigational Site Number : 1240019	Calgary	Alberta
Canada	Investigational Site Number : 1240028	Regina	Saskatchewan
Canada	Investigational Site Number : 1240012	Toronto	Ontario
Chile	Investigational Site Number : 1520001	Santiago	Reg Metropolitana De Santiago
Chile	Investigational Site Number : 1520002	Santiago	Reg Metropolitana De Santiago
Chile	Investigational Site Number : 1520003	Santiago	Reg Metropolitana De Santiago
Chile	Investigational Site Number : 1520010	Santiago	Reg Metropolitana De Santiago
China	Investigational Site Number : 1560041	Shenyang
France	Investigational Site Number : 2500011	Bordeaux
France	Investigational Site Number : 2500001	Lille
France	Investigational Site Number : 2500012	Rouen
Germany	Investigational Site Number : 2762202	Blankenfelde-Mahlow
Israel	Investigational Site Number : 3760008	Ramat Gan
Israel	Investigational Site Number : 3760007	Tel-Aviv
Japan	Investigational Site Number : 3923109	Habikino-shi
Japan	Investigational Site Number : 3920001	Tachikawa-shi	Tokyo
Japan	Investigational Site Number : 3923113	Yokohama-Shi	Kanagawa
Korea, Republic of	Investigational Site Number : 4100015	Incheon	Incheon-gwangyeoksi
Korea, Republic of	Investigational Site Number : 4100014	Seongnam	Gyeonggi-do
Korea, Republic of	Investigational Site Number : 4100001	Seoul	Gyeonggi-do
Korea, Republic of	Investigational Site Number : 4100007	Seoul	Seoul-teukbyeolsi
Spain	Investigational Site Number : 7240002	Badalona	Catalunya [Cataluña]
Spain	Investigational Site Number : 7242503	Madrid	Madrid, Comunidad De
Spain	Investigational Site Number : 7240017	Majadahonda	Madrid
Spain	Investigational Site Number : 7240016	Pozuelo de Alarcon	Madrid
Turkey	Investigational Site Number : 7920005	Istanbul
Turkey	Investigational Site Number : 7920008	Sahinbey
United Kingdom	Investigational Site Number : 8260013	Bristol
United Kingdom	Investigational Site Number : 8260009	Leeds	North Yorkshire
United Kingdom	Investigational Site Number : 8260015	London	London, City Of
United Kingdom	Investigational Site Number : 8262603	London	London, City Of
United Kingdom	Investigational Site Number : 8260012	Plymouth	Devon
United Kingdom	Investigational Site Number : 8260003	Portsmouth	Hampshire
United Kingdom	Investigational Site Number : 8260010	Sutton-in-Ashfield	Nottinghamshire
United States	Encore Medical Research of Boynton Beach LLC. Site Number : 8401030	Boynton Beach	Florida
United States	Encino Research Center Site Number : 8401042	Encino	California
United States	Center for Dermatology Clinical Research Site Number : 8401018	Fremont	California
United States	Dawes Fretzin Clinical Research Group, LLC Site Number : 8401015	Indianapolis	Indiana
United States	Long Beach Clinical Trials Site Number : 8401188	Long Beach	California
United States	LA Universal Research Center Site Number : 8401064	Los Angeles	California
United States	Sadick Research Group Site Number : 8401050	New York	New York
United States	Virginia Dermatology Skin Cancer Center Site Number : 8401047	Norfolk	Virginia
United States	Advanced Research Institute Site Number : 8401057	Ogden	Utah
United States	Skin Specialists Site Number : 8401068	Omaha	Nebraska
United States	Clinical Research Philadelphia Site Number : 8401193	Philadelphia	Pennsylvania
United States	Paddington Testing Company Site Number : 8401041	Philadelphia	Pennsylvania
United States	Global Clinical Professionals (GCP) Site Number : 8401045	Saint Petersburg	Florida
United States	Center for Dermatology and Plastic Surgery/ CCT Research Site Number : 8401119	Scottsdale	Arizona
United States	Avita Clinical Research Site Number : 8401073	Tampa	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Sanofi

Countries where clinical trial is conducted

United States,  Argentina,  Brazil,  Canada,  Chile,  China,  France,  Germany,  Israel,  Japan,  Korea, Republic of,  Spain,  Turkey,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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 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).	Week 36
Primary	EU, EU reference countries, and Japan: Proportion of participants reaching 75% reduction from baseline in Eczema Area and Severity Index (EASI) score (EASI75) at 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.	Week 36
Primary	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	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).	Week 36
Secondary	Proportion of participants reaching EASI-75 at Week 24 (for US and US reference countries only)	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. EASI-75 is 75% reduction from baseline in EASI score.	Week 36
Secondary	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)	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).	Baseline to Week 36
Secondary	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	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.	Baseline to Week 36
Secondary	Proportion of participants reaching EASI-75	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. EASI-75 is 75% reduction from baseline in EASI score.	Baseline to Week 24
Secondary	Proportion of participants with vIGA-AD of 0 (clear) or 1 (almost clear) and a reduction from baseline of =2 points	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).	Baseline to Week 24
Secondary	Proportion of participants reaching EASI-90	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. EASI-90 is 90% reduction from baseline in EASI score.	Baseline to Week 36
Secondary	Proportion of participants reaching EASI-100	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. EASI-100 is 100% reduction from baseline in EASI score.	Baseline to Week 36
Secondary	Proportion of participants with PP-NRS 0 or 1	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.	Baseline to Week 36
Secondary	Change in Dermatology Life Quality Index (DLQI) from baseline in participants with age =16 years old	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.	Baseline to Week 36
Secondary	Proportion of participants with a reduction in DLQI =4 from baseline in participants with age =16 years old and with DLQI baseline =4	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.	Baseline to Week 36
Secondary	Change in Children Dermatology Life Quality Index (CDLQI) from baseline in participants with age =12 to <16 years	The CDLQI is a validated 10-item questionnaire to measure dermatology-specific quality of life (QoL) in children aged 4-<16 years. Overall scoring ranges from 0 to 30, with a higher score indicating a poorer QoL.	Baseline to Week 36
Secondary	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	The CDLQI is a validated 10-item questionnaire to measure dermatology-specific quality of life (QoL) in children aged 4-<16 years. Overall scoring ranges from 0 to 30, with a higher score indicating a poorer QoL.	Baseline to Week 36
Secondary	Change in Hospital Anxiety Depression Scale (HADS) from baseline	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.	Baseline to Week 36
Secondary	Proportion of participants with HADS subscale Anxiety (HADS-A) <8 in participants with baseline HADS-A =8	HADS-A score ranges 0-21 with higher score indicating a poorer state.	Baseline to Week 36
Secondary	Proportion of participants with HADS subscale Depression (HADS-D) <8 in participants with HADS-D baseline =8	HADS-D score ranges 0-21 with higher score indicating a poorer state.	Baseline to Week 36
Secondary	Absolute change in weekly average of daily Skin Pain-Numerical Rating Scale (SP-NRS) from baseline	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.	Baseline to Week 36
Secondary	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	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.	Baseline to Week 36
Secondary	Absolute change in weekly average of daily Sleep Disturbance-Numerical Rating Scale (SD-NRS) from baseline	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.	Baseline to Week 36
Secondary	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	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.	Baseline to Week 36
Secondary	Percent change in EASI score from baseline	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.	Baseline to Week 36
Secondary	Percent change in weekly average of daily PP-NRS from baseline	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.	Baseline to Week 36
Secondary	Absolute change in weekly average of daily PP-NRS from baseline	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.	Baseline to Week 36
Secondary	Proportion of participants reaching EASI-50	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. EASI-50 is 50% reduction from baseline in EASI score.	Baseline to Week 36
Secondary	Proportion of participants with EASI =7	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.	Baseline to Week 36
Secondary	Change in percent Body Surface Area (BSA) affected by AD from baseline		Baseline to Week 36
Secondary	Percent change in Scoring Atopic Dermatitis (SCORAD) index from baseline	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).	Baseline to Week 36
Secondary	Absolute change in SCORAD index from baseline	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).	Baseline to Week 36
Secondary	Proportion of participants with a reduction in SCORAD = 8.7 points from baseline in participants with baseline SCORAD score = 8.7	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).	Baseline to Week 36
Secondary	Proportion of participants with a reduction in Patient Oriented Eczema Measure (POEM) =4 from baseline in participants with POEM Baseline =4	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.	Baseline to Week 36
Secondary	Change in POEM from baseline	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.	Baseline to Week 36
Secondary	Proportion of participants with rescue medication use		Baseline to Week 36
Secondary	Time to onset of effect on PP-NRS as measured by proportion of participants with an improvement (reduction) in PP-NRS by =4	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.	Baseline to Week 36
Secondary	Percentage of TCS/TCI free days		Baseline to Week 36
Secondary	Percentage of participants who experienced Treatment-Emergent Adverse Events (TEAEs), experienced Treatment-Emergent Serious Adverse Events (TESAEs) and/or Treatment-Emergent Adverse Events of Special Interest (AESI)		Baseline to Week 52
Secondary	Serum amlitelimab concentrations		Baseline to Week 52
Secondary	Incidence of antidrug antibodies (ADAs) of amlitelimab		Baseline to Week 52
Secondary	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	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).	Baseline to Week 36
Secondary	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	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. EASI-75 is 75% reduction from baseline in EASI score.	Baseline to Week 36