Clinical trial NCT06058156: Phase 2 Study of SAR444656 in Adult Participants With Moderate to Severe Atopic Dermatitis
Official title: A Multinational, Multicenter, Double-blind, Placebo-controlled Phase 2 Study to Evaluate Efficacy and Safety of SAR444656 in Adult Participants With Moderate to Severe Atopic Dermatitis
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Atopic Dermatitis
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
Collaborators: name: Kymera Therapeutics, Inc.
First posted: 2023-09-28
Enrollment: 200
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a multinational, multicenter, double-blind, placebo-controlled, parallel-group Phase 2, 4-arm study in adult participants with moderate to severe AD who are inadequately controlled with topical therapies or for whom such topical therapies are inadvisable and who are candidates for systemic therapy.

Participants will be randomized to receive SAR444656 dose 1, dose 2, dose 3 or matching placebo.

Participants who meet inclusion/exclusion criteria will be stratified for randomization by severity of AD (moderate \[baseline EASI score \<22\] versus severe \[baseline EASI score ≥22\]).

The total duration of study is approximately 24 weeks, including 1 to 4 weeks for screening, 16 weeks for double-blind study treatment and 4 weeks for follow-up.


Eligibility criteria: Inclusion Criteria:

* Participants with atopic dermatitis as defined by the American Academy of Dermatology Consensus Criteria for at least 1 year before the baseline visit.
* EASI ≥12 at screening and at baseline visit
* vIGA score ≥3 (on the 0 to 4 IGA scale, in which 3 is moderate and 4 is severe) at screening and baseline visit.
* AD involvement ≥10% of BSA at screening and baseline visit
* Baseline PP-NRS ≥4
* Participants must have documented history within 6 months prior to baseline visit, of either inadequate response or inadvisability to topical medications
* Participants must have applied daily topical emollient (moisturizer) for at least the 7 consecutive days immediately before the baseline visit. Participants should continue using daily moisturizers during the study.
* Participants must be willing and able to complete the electronic diary for the duration of the study as required by the study protocol.
* Contraceptive use by men and women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.

Exclusion Criteria:

* Presence of other skin conditions that may interfere with study assessments such as psoriasis, tinea corporis, lupus erythematosus
* Any active or chronic infection requiring systemic treatment within 4 weeks prior to baseline
* Known history of, or suspected, significant current immunosuppression, including history of invasive opportunistic or helminth infections despite infection resolution or otherwise recurrent infections of abnormal frequency or prolonged duration.
* History of solid organ or stem cell transplant.
* Participants with history of splenectomy.
* Participants with history of any malignancy or lymphoproliferative disease, except if the participant has been free from disease for ≥5 years. Successfully treated non-metastatic cutaneous squamous cell carcinoma, basal cell carcinoma, or localized carcinoma in situ of the cervix are allowed.
* Family history of sudden death or long QT syndrome.
* History of congenital or drug-induced long QT syndrome.
* Congestive heart failure (NYHA Class 2-4), greater than Class 1 angina pectoris, acute coronary syndrome within prior 6 months, known structural heart disease.
* History of any major cardiovascular events (eg, myocardial infarction, unstable angina pectoris, coronary revascularization, stroke, or transient ischemic attack) at any time prior to screening.
* History of ventricular fibrillation, ventricular tachycardia, Torsades de Pointes, atrial fibrillation, syncope not explained by non-cardiac etiology.
* Uncontrolled hypertension defined as consistent systolic blood pressure ≥150 mm Hg or consistent diastolic blood pressure ≥90 mm Hg despite antihypertensive medication.
* Participants had major surgery within 4 weeks prior to the screening or have planned any elective major surgery during the study.
* Having received any of protocol-specified prohibited therapy (Topical or systemic) within the specified timeframe prior to the baseline visit.

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

Primary outcomes:
measure: Percent change from baseline in EASI
timeFrame: Week 16
Secondary outcomes:
measure: Proportion of participants with validated Investigational Global Assessment (vIGA)-AD of 0 or 1 and a reduction from baseline of ≥2 points
timeFrame: Week 16
measure: Proportion of participants achieving EASI-75 (reduction of EASI score by ≥75% from baseline)
timeFrame: Week 16
measure: Absolute change from baseline in EASI
timeFrame: Week 16
measure: Proportion of participants achieving EASI-50 (reduction of EASI score by ≥50% from baseline)
timeFrame: Week 16
measure: Proportion of participants achieving EASI-90 (reduction of EASI score by ≥90% from baseline)
timeFrame: Week 16
measure: Change from baseline in percent body surface area (BSA) affected by AD
timeFrame: Week 16
measure: Proportion of participants with reduction of weekly average of daily peak pruritus numeric rating scale (PP-NRS) by ≥4 points from baseline
timeFrame: Week 16
measure: Percent change from baseline in weekly average of daily PP-NRS
timeFrame: Week 16
measure: Absolute change from baseline in weekly average of daily PP-NRS
timeFrame: Week 16
measure: Incidence of treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), and adverse events of special interest (AESIs), investigational medicinal product (IMP) discontinuation due to TEAEs
timeFrame: Up to Week 20
measure: Plasma SAR444656 concentration
timeFrame: Week 0, Week 1, Week 2, Week 4, and Week 16
Other outcomes:
Locations:
city: Scottsdale
country: United States
facility: Clear Dermatology & Aesthetics Center- Site Number : 8400003
state: Arizona
city: Boynton Beach
country: United States
facility: Encore Medical Research of Boynton Beach- Site Number : 8400002
state: Florida
city: Doral
country: United States
facility: Revival Research - Doral- Site Number : 8400007
state: Florida
city: Hollywood
country: United States
facility: Encore Medical Research - 6600 Taft St- Site Number : 8400004
state: Florida
city: Miami
country: United States
facility: Sullivan Dermatology- Site Number : 8400001
state: Florida
city: Weston
country: United States
facility: Encore Medical Research - Weston- Site Number : 8400008
state: Florida
city: Dearborn
country: United States
facility: Wayne Health - Dearborn- Site Number : 8400009
state: Michigan
city: Pittsburgh
country: United States
facility: UPMC Montefiore- Site Number : 8400006
state: Pennsylvania
city: Carrollton
country: United States
facility: ACRC Trials - Carrollton - Hunt - PPDS- Site Number : 8400012
state: Texas
city: Ostrava
country: Czechia
facility: Investigational Site Number : 2030002
city: Pardubice
country: Czechia
facility: Investigational Site Number : 2030001
city: Prague
country: Czechia
facility: Investigational Site Number : 2030003
city: Heidelberg
country: Germany
facility: Investigational Site Number : 2760007
state: Baden-Württemberg
city: Munich
country: Germany
facility: Investigational Site Number : 2760009
state: Bayern
city: Frankfurt
country: Germany
facility: Investigational Site Number : 2760008
state: Hessen
city: Buxtehude
country: Germany
facility: Investigational Site Number : 2760002
state: Niedersachsen
city: Bochum
country: Germany
facility: Investigational Site Number : 2760003
state: Nordrhein-Westfalen
city: Remscheid
country: Germany
facility: Investigational Site Number : 2760006
state: Nordrhein-Westfalen
city: Dessau
country: Germany
facility: Investigational Site Number : 2760010
state: Sachsen-Anhalt
city: Berlin
country: Germany
facility: Investigational Site Number : 2760001
city: Pavlos Melas
country: Greece
facility: Investigational Site Number : 3000001
state: Thessaloniki
city: Thessaloniki
country: Greece
facility: Investigational Site Number : 3000002
city: Cheonan-si
country: Korea, Republic of
facility: Investigational Site Number : 4100002
state: Chungcheongnam-do
city: Seongbuk-Gu
country: Korea, Republic of
facility: Investigational Site Number : 4100004
state: Seoul-teukbyeolsi
city: Wroclaw
country: Poland
facility: Investigational Site Number : 6160012
state: Dolnoslaskie
city: Wroclaw
country: Poland
facility: Investigational Site Number : 6160002
state: Dolnoslaskie
city: Lodz
country: Poland
facility: Investigational Site Number : 6160011
state: Lódzkie
city: Lodz
country: Poland
facility: Investigational Site Number : 6160001
state: Lódzkie
city: Tarnow
country: Poland
facility: Investigational Site Number : 6160006
state: Malopolskie
city: Warsaw
country: Poland
facility: Investigational Site Number : 6160007
state: Mazowieckie
city: Warsaw
country: Poland
facility: Investigational Site Number : 6160005
state: Mazowieckie
city: Chojnice
country: Poland
facility: Investigational Site Number : 6160003
state: Pomorskie
city: Gdansk
country: Poland
facility: Investigational Site Number : 6160004
state: Pomorskie
city: Katowice
country: Poland
facility: Investigational Site Number : 6160009
state: Slaskie
city: Lodz
country: Poland
facility: Investigational Site Number : 6160010
Study officials:
References: