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
Overview
- Phase
- Phase 2
- Intervention
- SAR444656 (KT-474)
- Conditions
- Atopic Dermatitis
- Sponsor
- Sanofi
- Enrollment
- 70
- Locations
- 37
- Primary Endpoint
- Percent change from baseline in EASI
- Status
- Terminated
- Last Updated
- 4 months ago
Overview
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.
Investigators
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.
Arms & Interventions
SAR444656 dose 1
Participants will receive SAR444656 dose 1 orally
Intervention: SAR444656 (KT-474)
SAR444656 dose 2
Participants will receive SAR444656 dose 2 orally
Intervention: SAR444656 (KT-474)
SAR444656 dose 3
Participants will receive SAR444656 dose 3 orally
Intervention: SAR444656 (KT-474)
Placebo
Participants will receive placebo orally
Intervention: Placebo
Outcomes
Primary Outcomes
Percent change from baseline in EASI
Time Frame: Week 16
Eczema area severity index is an Investigator-assessed validated tool used to measure the extent (area) and severity of atopic dermatitis (AD). Total score ranges from 0 to 72 with a higher score indicating increased extent and severity of AD.
Secondary Outcomes
- Absolute change from baseline in weekly average of daily PP-NRS(Week 16)
- 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(Up to Week 20)
- Proportion of participants achieving EASI-90 (reduction of EASI score by ≥90% from baseline)(Week 16)
- Change from baseline in percent body surface area (BSA) affected by AD(Week 16)
- Proportion of participants with reduction of weekly average of daily peak pruritus numeric rating scale (PP-NRS) by ≥4 points from baseline(Week 16)
- Percent change from baseline in weekly average of daily PP-NRS(Week 16)
- Plasma SAR444656 concentration(Week 0, Week 1, Week 2, Week 4, and Week 16)
- Proportion of participants with validated Investigational Global Assessment (vIGA)-AD of 0 or 1 and a reduction from baseline of ≥2 points(Week 16)
- Proportion of participants achieving EASI-75 (reduction of EASI score by ≥75% from baseline)(Week 16)
- Proportion of participants achieving EASI-50 (reduction of EASI score by ≥50% from baseline)(Week 16)
- Absolute change from baseline in EASI(Week 16)