Clinical trial NCT06241118: 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
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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Dermatitis Atopic
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
First posted: 2024-02-05
Enrollment: 249
Sex: ALL
Minimum age (years): 12
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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).


Eligibility criteria: 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

Primary outcomes:
measure: 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
timeFrame: Week 36
measure: 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
timeFrame: Week 36
measure: 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
timeFrame: Week 36
measure: Percent change in weekly average of daily SD-NRS
timeFrame: Baseline to Week 36
Secondary outcomes:
measure: Proportion of participants reaching EASI-75 at Week 24 (for US and US reference countries only)
timeFrame: Week 36
measure: 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 and a reduction from baseline of ≥2 points)
timeFrame: Baseline to Week 36
measure: 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
timeFrame: Baseline to Week 36
measure: Proportion of participants reaching EASI-75
timeFrame: Baseline to Week 24
measure: Proportion of participants with vIGA-AD of 0 (clear) or 1 (almost clear) and a reduction from baseline of ≥2 points
timeFrame: Baseline to Week 24
measure: Proportion of participants reaching EASI-90
timeFrame: Baseline to Week 36
measure: Proportion of participants reaching EASI-100
timeFrame: Baseline to Week 36
measure: Proportion of participants with PP-NRS 0 or 1
timeFrame: Baseline to Week 36
measure: Change in Dermatology Life Quality Index (DLQI) from baseline in participants with age ≥16 years old
timeFrame: Baseline to Week 36
measure: Proportion of participants with a reduction in DLQI ≥4 from baseline in participants with age ≥16 years old and with DLQI baseline ≥4
timeFrame: Baseline to Week 36
measure: Change in Children Dermatology Life Quality Index (CDLQI) from baseline in participants with age ≥12 to <16 years
timeFrame: Baseline to Week 36
measure: 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
timeFrame: Baseline to Week 36
measure: Change in Hospital Anxiety Depression Scale (HADS) from baseline
timeFrame: Baseline to Week 36
measure: Proportion of participants with HADS subscale Anxiety (HADS-A) <8 in participants with baseline HADS-A ≥8
timeFrame: Baseline to Week 36
measure: Proportion of participants with HADS subscale Depression (HADS-D) <8 in participants with HADS-D baseline ≥8
timeFrame: Baseline to Week 36
measure: Absolute change in weekly average of daily Skin Pain-Numerical Rating Scale (SP-NRS) from baseline
timeFrame: Baseline to Week 36
measure: 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
timeFrame: Baseline to Week 36
measure: Percent change in weekly average of daily SP-NRS from baseline
timeFrame: Baseline to Week 36
measure: Proportion of participants with vIGA-AD 0 (clear)
timeFrame: Baseline to Week 36
measure: Absolute change in weekly average of daily Sleep Disturbance-Numerical Rating Scale (SD-NRS) from baseline
timeFrame: Baseline to Week 36
measure: 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
timeFrame: Baseline to Week 36
measure: Percent change in weekly average of daily SD-NRS
timeFrame: Baseline to Week 36
measure: Percent change in EASI score from baseline
timeFrame: Baseline to Week 36
measure: Percent change in weekly average of daily PP-NRS from baseline
timeFrame: Baseline to Week 36
measure: Absolute change in weekly average of daily PP-NRS from baseline
timeFrame: Baseline to Week 36
measure: Proportion of participants reaching EASI-50
timeFrame: Baseline to Week 36
measure: Proportion of participants with EASI ≤7
timeFrame: Baseline to Week 36
measure: Change in percent Body Surface Area (BSA) affected by AD from baseline
timeFrame: Baseline to Week 36
measure: Percent change in Scoring Atopic Dermatitis (SCORAD) index from baseline
timeFrame: Baseline to Week 36
measure: Absolute change in SCORAD index from baseline
timeFrame: Baseline to Week 36
measure: Proportion of participants with a reduction in SCORAD ≥ 8.7 points from baseline in participants with baseline SCORAD score ≥ 8.7
timeFrame: Baseline to Week 36
measure: Proportion of participants with a reduction in Patient Oriented Eczema Measure (POEM) ≥4 from baseline in participants with POEM Baseline ≥4
timeFrame: Baseline to Week 36
measure: Change in POEM from baseline
timeFrame: Baseline to Week 36
measure: Proportion of participants with rescue medication use
timeFrame: Baseline to Week 36
measure: Time to onset of effect on PP-NRS as measured by proportion of participants with an improvement (reduction) in PP-NRS by ≥4
timeFrame: Baseline to Week 36
measure: Percentage of TCS/TCI free days
timeFrame: Baseline to Week 36
measure: 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)
timeFrame: Baseline to Week 52
measure: Serum amlitelimab concentrations
timeFrame: Baseline to Week 52
measure: Incidence of antidrug antibodies (ADAs) of amlitelimab
timeFrame: Baseline to Week 52
measure: 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
timeFrame: Baseline to Week 36
measure: 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
timeFrame: Baseline to Week 36
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham- Site Number : 8401267
state: Alabama
city: Scottsdale
country: United States
facility: Center for Dermatology and Plastic Surgery- Site Number : 8401119
state: Arizona
city: North Little Rock
country: United States
facility: Arkansas Dermatology - North Little Rock- Site Number : 8401244
state: Arkansas
city: Encino
country: United States
facility: Encino Research Center- Site Number : 8401042
state: California
city: Fremont
country: United States
facility: Center for Dermatology Clinical Research- Site Number : 8401018
state: California
city: Long Beach
country: United States
facility: Long Beach Clinical Trials- Site Number : 8401188
state: California
city: Los Angeles
country: United States
facility: Dermatology Research Associates - Los Angeles- Site Number : 8401092
state: California
city: Los Angeles
country: United States
facility: LA Universal Research Center- Site Number : 8401064
state: California
city: San Diego
country: United States
facility: Therapeutics Clinical Research- Site Number : 8401283
state: California
city: Wheat Ridge
country: United States
facility: Paradigm Research - Wheat Ridge- Site Number : 8401245
state: Colorado
city: Boynton Beach
country: United States
facility: Encore Medical Research of Boynton Beach- Site Number : 8401030
state: Florida
city: Doral
country: United States
facility: St Jude Clinical Research- Site Number : 8401287
state: Florida
city: Saint Petersburg
country: United States
facility: Global Clinical Professionals (GCP)- Site Number : 8401045
state: Florida
city: Tampa
country: United States
facility: Avita Clinical Research- Site Number : 8401073
state: Florida
city: Skokie
country: United States
facility: NorthShore University HealthSystem - Skokie- Site Number : 8401038
state: Illinois
city: Indianapolis
country: United States
facility: Dawes Fretzin Clinical Research- Site Number : 8401015
state: Indiana
city: Franklin
country: United States
facility: Access Dermatology Clinic- Site Number : 8401296
state: Kentucky
city: Metairie
country: United States
facility: Tandem Clinical Research, LLC- Site Number : 8401187
state: Louisiana
city: Ann Arbor
country: United States
facility: University of Michigan Medical Center- Site Number : 8401290
state: Michigan
city: Northville
country: United States
facility: MI Skin Center- Site Number : 8401307
state: Michigan
city: Omaha
country: United States
facility: Skin Specialists- Site Number : 8401068
state: Nebraska
city: Albuquerque
country: United States
facility: University of New Mexico Comprehensive Cancer Center- Site Number : 8401263
state: New Mexico
city: New York
country: United States
facility: Equity Medical- Site Number : 8401239
state: New York
city: New York
country: United States
facility: Sadick Research Group - New York - Park Avenue- Site Number : 8401050
state: New York
city: Portland
country: United States
facility: Oregon Health and Science University- Site Number : 8401247
state: Oregon
city: Philadelphia
country: United States
facility: Paddington Testing Company- Site Number : 8401041
state: Pennsylvania
city: Philadelphia
country: United States
facility: Clinical Research of Philadelphia- Site Number : 8401193
state: Pennsylvania
city: Charleston
country: United States
facility: Medical University of South Carolina - Charleston - Jonathan Lucas Street- Site Number : 8401282
state: South Carolina
city: Arlington
country: United States
facility: Arlington Research Center- Site Number : 8401248
state: Texas
city: Dallas
country: United States
facility: Reveal Research Institute - Dallas- Site Number : 8401219
state: Texas
city: Ogden
country: United States
facility: Advanced Research Institute - Odgen- Site Number : 8401057
state: Utah
city: Norfolk
country: United States
facility: Virginia Dermatology & Skin Cancer Center- Site Number : 8401047
state: Virginia
city: Mill Creek
country: United States
facility: North Sound Dermatology- Site Number : 8401280
state: Washington
city: Milwaukee
country: United States
facility: Children's Wisconsin- Site Number : 8401246
state: Wisconsin
city: Cheyenne
country: United States
facility: Cheyenne Skin Clinic- Site Number : 8401234
state: Wyoming
city: Rosario
country: Argentina
facility: Investigational Site Number : 0320007
state: Santa Fe
city: Buenos Aires
country: Argentina
facility: Investigational Site Number : 0320011
city: Buenos Aires
country: Argentina
facility: Investigational Site Number : 0320019
city: Córdoba
country: Argentina
facility: Investigational Site Number : 0320014
city: Melbourne
country: Australia
facility: Investigational Site Number : 0360008
state: Victoria
city: Melbourne
country: Australia
facility: Investigational Site Number : 0360006
state: Victoria
city: Salvador
country: Brazil
facility: Centro de Pesquisas da Clínica IBIS- Site Number : 0760002
state: Bahia
city: Porto Alegre
country: Brazil
facility: Irmandade da Santa Casa de Misericórdia de Porto Alegre- Site Number : 0760005
state: Rio Grande Do Sul
city: Santo André
country: Brazil
facility: Faculdade de Medicina do ABC- Site Number : 0760001
state: São Paulo
city: Sorocaba
country: Brazil
facility: Clinica de Alergia Martti Antila- Site Number : 0760006
state: São Paulo
city: São Paulo
country: Brazil
facility: Hospital Alemao Oswaldo Cruz - São Paulo- Site Number : 0760010
city: São Paulo
country: Brazil
facility: Centro de Desenvolvimento em Estudos ClÌnicos Brasil- Site Number : 0760014
city: Calgary
country: Canada
facility: Investigational Site Number : 1240019
state: Alberta
city: Edmonton
country: Canada
facility: Investigational Site Number : 1240016
state: Alberta
city: Burlington
country: Canada
facility: Investigational Site Number : 1240058
state: Ontario
city: Hamilton
country: Canada
facility: Investigational Site Number : 1240020
state: Ontario
city: London
country: Canada
facility: Investigational Site Number : 1240053
state: Ontario
city: Toronto
country: Canada
facility: Investigational Site Number : 1240012
state: Ontario
city: Toronto
country: Canada
facility: Investigational Site Number : 1240054
state: Ontario
city: Regina
country: Canada
facility: Investigational Site Number : 1240028
state: Saskatchewan
city: Santiago
country: Chile
facility: Investigational Site Number : 1520002
state: Reg Metropolitana De Santiago
city: Santiago
country: Chile
facility: Investigational Site Number : 1520003
state: Reg Metropolitana De Santiago
city: Santiago
country: Chile
facility: Investigational Site Number : 1520010
state: Reg Metropolitana De Santiago
city: Santiago
country: Chile
facility: Investigational Site Number : 1520005
state: Reg Metropolitana De Santiago
city: Santiago
country: Chile
facility: Investigational Site Number : 1520001
state: Reg Metropolitana De Santiago
city: Changchun
country: China
facility: Investigational Site Number : 1560031
city: Guangzhou
country: China
facility: Investigational Site Number : 1560021
city: Guangzhou
country: China
facility: Investigational Site Number : 1560036
city: Hangzhou
country: China
facility: Investigational Site Number : 1560044
city: Hangzhou
country: China
facility: Investigational Site Number : 1560002
city: Hangzhou
country: China
facility: Investigational Site Number : 1560009
city: Nanyang
country: China
facility: Investigational Site Number : 1560034
city: Ningbo
country: China
facility: Investigational Site Number : 1560024
city: Ningbo
country: China
facility: Investigational Site Number : 1560035
city: Shanghai
country: China
facility: Investigational Site Number : 1560001
city: Shenyang
country: China
facility: Investigational Site Number : 1560041
city: Wuhan
country: China
facility: Investigational Site Number : 1560038
city: Xi An
country: China
facility: Investigational Site Number : 1560032
city: Bordeaux
country: France
facility: Investigational Site Number : 2500011
city: Clermont-ferrand
country: France
facility: Investigational Site Number : 2500014
city: Créteil
country: France
facility: Investigational Site Number : 2500004
city: Lille
country: France
facility: Investigational Site Number : 2500001
city: Paris
country: France
facility: Investigational Site Number : 2500017
city: Rouen
country: France
facility: Investigational Site Number : 2500012
city: Saint Pierre
country: France
facility: Investigational Site Number : 2500016
city: Berlin
country: Germany
facility: Investigational Site Number : 2762203
city: Blankenfelde-mahlow
country: Germany
facility: Investigational Site Number : 2762202
city: Dresden
country: Germany
facility: Investigational Site Number : 2761001
city: Lübeck
country: Germany
facility: Investigational Site Number : 2761002
city: Witten
country: Germany
facility: Investigational Site Number : 2760019
city: Athens
country: Greece
facility: Investigational Site Number : 3000004
city: Athens
country: Greece
facility: Investigational Site Number : 3000001
city: Athens
country: Greece
facility: Investigational Site Number : 3000005
city: Thessaloniki
country: Greece
facility: Investigational Site Number : 3000002
city: Be'er Sheva
country: Israel
facility: Investigational Site Number : 3760005
city: Ramat Gan
country: Israel
facility: Investigational Site Number : 3760008
city: Tel Aviv
country: Israel
facility: Investigational Site Number : 3760007
city: Naples
country: Italy
facility: Investigational Site Number : 3800017
state: Napoli
city: Turin
country: Italy
facility: Investigational Site Number : 3800020
state: Torino
city: Chieti
country: Italy
facility: Investigational Site Number : 3800016
city: Modena
country: Italy
facility: Investigational Site Number : 3800021
city: Perugia
country: Italy
facility: Investigational Site Number : 3800015
city: Yokohama-Shi
country: Japan
facility: Investigational Site Number : 3923113
state: Kanagawa
city: Yokohama
country: Japan
facility: Investigational Site Number : 3923113
state: Kanagawa
city: Habikino
country: Japan
facility: Investigational Site Number : 3923109
state: Osaka
city: Sakai
country: Japan
facility: Investigational Site Number : 3923110
state: Osaka
city: Mibu
country: Japan
facility: Investigational Site Number : 3923106
state: Tochigi
city: Tachikawa
country: Japan
facility: Investigational Site Number : 3920001
state: Tokyo
city: Hiroshima
country: Japan
facility: Investigational Site Number : 3920007
city: Ansan-si
country: Korea, Republic of
facility: Investigational Site Number : 4100002
state: Gyeonggi-do
city: Seongnam-si
country: Korea, Republic of
facility: Investigational Site Number : 4100014
state: Gyeonggi-do
city: Bupyeong-gu
country: Korea, Republic of
facility: Investigational Site Number : 4100015
state: Incheon-gwangyeoksi
city: Seoul
country: Korea, Republic of
facility: Investigational Site Number : 4100007
state: Seoul-teukbyeolsi
city: Seoul
country: Korea, Republic of
facility: Investigational Site Number : 4100001
state: Seoul-teukbyeolsi
city: Monterrey
country: Mexico
facility: Investigational Site Number : 4840011
state: Nuevo León
city: Veracruz
country: Mexico
facility: Investigational Site Number : 4840003
city: Rotterdam
country: Netherlands
facility: Investigational Site Number : 5280004
city: Utrecht
country: Netherlands
facility: Investigational Site Number : 5280001
city: Wroclaw
country: Poland
facility: Investigational Site Number : 6162417
state: Dolnoslaskie
city: Lublin
country: Poland
facility: Investigational Site Number : 6160002
state: Lubelskie
city: Warsaw
country: Poland
facility: Investigational Site Number : 6162411
state: Mazowieckie
city: Warsaw
country: Poland
facility: Investigational Site Number : 6160001
state: Mazowieckie
city: Gdansk
country: Poland
facility: Investigational Site Number : 6160006
state: Pomorskie
city: Riyadh
country: Saudi Arabia
facility: Investigational Site Number : 6820001
city: Badalona
country: Spain
facility: Investigational Site Number : 7240002
state: Barcelona [Barcelona]
city: Majadahonda
country: Spain
facility: Investigational Site Number : 7240017
state: Madrid
city: Pozuelo de Alarcón
country: Spain
facility: Investigational Site Number : 7240016
state: Madrid
city: Seville
country: Spain
facility: Investigational Site Number : 7240020
state: Sevilla
city: Alicante
country: Spain
facility: Investigational Site Number : 7242505
city: Madrid
country: Spain
facility: Investigational Site Number : 7242503
city: Kaohsiung City
country: Taiwan
facility: Investigational Site Number : 1583201
city: Taipei City
country: Taiwan
facility: Investigational Site Number : 1580001
city: Taipei
country: Taiwan
facility: Investigational Site Number : 1580003
city: Taoyuan City
country: Taiwan
facility: Investigational Site Number : 1583203
city: Gaziantep
country: Turkey
facility: Investigational Site Number : 7920008
city: Istanbul
country: Turkey
facility: Investigational Site Number : 7920005
city: Istanbul
country: Turkey
facility: Investigational Site Number : 7920002
city: Abu Dhabi
country: United Arab Emirates
facility: Investigational Site Number : 7840001
city: Abu Dhabi
country: United Arab Emirates
facility: Investigational Site Number : 7840002
city: Bristol
country: United Kingdom
facility: Investigational Site Number : 8260013
state: Bristol, City Of
city: Plymouth
country: United Kingdom
facility: Investigational Site Number : 8260012
state: Devon
city: London
country: United Kingdom
facility: Investigational Site Number : 8262603
state: England
city: London
country: United Kingdom
facility: Investigational Site Number : 8260015
state: England
city: Portsmouth
country: United Kingdom
facility: Investigational Site Number : 8260003
state: Hampshire
city: Leeds
country: United Kingdom
facility: Investigational Site Number : 8260009
state: North Yorkshire
city: Nottingham
country: United Kingdom
facility: Investigational Site Number : 8260010
state: Nottinghamshire
city: Liverpool
country: United Kingdom
facility: Investigational Site Number : 8260008
Study officials:
References: