Efficacy and Safety Evaluation of SAR444656 in Adults with Moderate to Severe Atopic Dermatitis: A Multinational, Double-Blind, Placebo-Controlled Phase 2 Study

Trial ID: 2023-504346-66-00
Protocol: ACT17754
Sponsor: Sanofi-Aventis Recherche & Developpement

Trial statistics

science

test molecules

location_city

research sites

public

countries

medical_information

disease

person_search

investigators

handshake

vendors

Diseases & Conditions

Dermatitis atopic

Objectives

The primary objective of this phase 2 study is to evaluate the **efficacy** of SAR444656 on atopic dermatitis (AD) lesions compared with placebo in adult participants with moderate to severe AD. This is clinically relevant as it aims to determine the potential of SAR444656 to improve skin lesions, which are a significant symptom of AD, thereby potentially enhancing patient quality of life.

Secondary objectives include:

Assessing the efficacy of SAR444656 on additional clinical assessments of AD compared with placebo.
Evaluating the efficacy of SAR444656 on patient-reported outcomes (PRO) compared with placebo.
Assessing the **safety** of SAR444656 in the study population.
Evaluating the **pharmacokinetic** profile of SAR444656 in adult participants with moderate to severe AD.

Participants

The clinical trial involves a total of **142 participants** diagnosed with **atopic dermatitis**. The study population includes both male and female adults, with an age range that encompasses individuals from 18 to 65 years. Participants were selected based on specific criteria, including a documented history of atopic dermatitis for at least one year prior to the baseline visit, and a requirement for moderate to severe disease severity as indicated by an EASI score of 12 or higher and a vIGA score of 3 or more. The trial population is characterized by individuals who have experienced inadequate response or inadvisability to topical medications within the last six months. Participants are required to have applied a daily topical emollient for at least seven consecutive days before the baseline visit and are expected to continue this regimen throughout the study. The trial also includes vulnerable populations, ensuring a comprehensive assessment of the treatment's efficacy across diverse demographic groups. Lifestyle considerations such as the consistent use of moisturizers and adherence to contraceptive guidelines are integral to the study protocol.

Plans and Procedures

The clinical trial is a **randomized**, **double-blind**, placebo-controlled phase 2 study designed to evaluate the efficacy and safety of SAR444656 in adult participants with moderate to severe **atopic dermatitis**. The trial aims to assess the efficacy of SAR444656 on atopic dermatitis lesions compared with placebo. The study is expected to commence recruitment on February 29, 2024, and conclude by August 18, 2026. Participants will be involved in the study for a maximum treatment period of 16 weeks, during which they will receive SAR444656 in the form of a film-coated tablet administered orally, with a maximum daily dose of 100 mg and a total dose not exceeding 11,300 mg.

The trial will include several study visits, beginning with a screening visit to confirm eligibility based on criteria such as a history of atopic dermatitis for at least one year, an EASI score of 12 or higher, and a vIGA score of 3 or more. Participants must also have at least 10% body surface area involvement and a baseline PP-NRS of 4 or higher. Following the screening, participants will attend a baseline visit to establish initial measurements and begin treatment. Throughout the study, follow-up visits will be scheduled to monitor progress, assess primary and secondary endpoints, and ensure participant safety. The primary endpoint is the percent change from baseline in the EASI score, while secondary endpoints include the proportion of participants achieving various levels of EASI improvement and changes in pruritus scores.

The end-of-study visit will occur after the 16-week treatment period, where final assessments will be conducted, including the evaluation of treatment-emergent adverse events and plasma SAR444656 concentration. Participants may be withdrawn from the study early if they experience significant adverse events, fail to adhere to the study protocol, or choose to discontinue participation. The study is conducted under strict adherence to ethical guidelines and regulatory requirements, ensuring the safety and well-being of all participants.

Treatment

The clinical trial involves the administration of **SAR444656**, an experimental medication, to evaluate its efficacy and safety in adult participants with moderate to severe atopic dermatitis. **SAR444656** is provided in the form of a **film-coated tablet**. The active substance, also named **SAR444656**, is of chemical origin. The medication is administered orally with a maximum daily dose of 100 mg. The total maximum dose over the treatment period is 11,300 mg, with the treatment duration not exceeding 16 weeks. The pharmaceutical development and supply of **SAR444656** are managed by Sanofi Aventis Recherche et Développement (SAR).

In addition to the experimental treatment, a **placebo** is used as a comparator in this double-blind, placebo-controlled study. The placebo is designed to match the experimental medication in appearance but does not contain the active substance. The use of a placebo allows for the assessment of the true efficacy of **SAR444656** by providing a baseline for comparison. The administration route and frequency for the placebo are identical to those of the experimental medication to maintain the study's blinding integrity.

Efficacy

The efficacy of SAR444656 in the treatment of moderate to severe **atopic dermatitis** will be assessed through a series of primary and secondary endpoints. The primary endpoint is the percent change from baseline in the Eczema Area and Severity Index (EASI). Secondary endpoints include the proportion of participants achieving a validated Investigational Global Assessment (vIGA)-AD score of 0 or 1 with a reduction of at least 2 points from baseline, and the proportion of participants achieving EASI-75, EASI-50, and EASI-90, which correspond to reductions in EASI scores by 75%, 50%, and 90% from baseline, respectively. Additional secondary endpoints involve the absolute change from baseline in EASI, change in the percent body surface area (BSA) affected by atopic dermatitis, and the proportion of participants with a reduction of at least 4 points in the weekly average of daily peak pruritus numeric rating scale (PP-NRS) from baseline. The percent and absolute changes from baseline in the weekly average of daily PP-NRS will also be evaluated.

Data collection will occur at specified timepoints throughout the study, with efficacy assessments conducted using validated scales and patient-reported outcomes. The incidence of treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), and adverse events of special interest (AESIs) will be monitored, along with investigational medicinal product (IMP) discontinuation due to TEAEs. Plasma concentrations of SAR444656 will be measured to support the evaluation of the drug's efficacy and safety profile. The study is designed as a multinational, multicenter, double-blind, placebo-controlled phase 2 trial, ensuring rigorous assessment of the investigational product's efficacy in the target population.

Inclusion and Exclusion Criteria

check_circle

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.

cancel

Exclusion Criteria

Presence of other skin conditions that may interfere with study assessments such as psoriasis, tinea corporis, lupus erythematosus.
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.
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.
Having received any of protocol-specified prohibited therapy (topical or systemic) within the specified timeframe prior to the baseline visit