Phase 2a Study of the Safety, Tolerability, and Pharmacokinetics of Topically Administered PRN473 (SAR444727) in Patients With Mild to Moderate Atopic Dermatitis

Study Overview
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Brief Summary
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This is a Ph2a study that consists of a double-blind, intra-patient placebo-controlled treatment period and an open-label uncontrolled treatment period with objective to evaluate the safety, tolerability, PK and preliminary efficacy of PRN473 in up to 40 patients with mild to moderate AD. On Day 1 (Baseline) of the Blinded Period, 2 target lesions with a difference no greater than 1 point in Total Sign Score (TSS) will be randomly assigned to treatment in an intra-patient 1:1 manner, one lesion to PRN473 and the other to matching placebo. Participation will take approximately 13 weeks, including up to a 5-week screening period, a 6-week treatment period, end of study assessments 1 day after last dose, and a safety follow-up phone call 2 weeks after last dose.

Detailed Description
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Study duration per patient is approximately 56 days including a 42-days treatment period.

Official Title
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A Randomized, Intra-patient, Double-blind, Placebo-controlled Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of Topically Administered PRN473 (SAR444727) in Patients With Mild to Moderate Atopic Dermatitis

Conditions
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Atopic Dermatitis

Intervention / Treatment
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* Drug: PRN473 (SAR444727)
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male and female adults 18 to 70 years of age (inclusive) at the time of informed consent. Diagnosed with mild to moderate AD. History of AD for at least 6 months as determined by the Investigator through patient interview. Stable disease for the 4 weeks prior to the screening visit with no significant flares in AD as determined by the Investigator. Validated Investigator Global Assessment-atopic dermatitis (vIGA-AD) score of Moderate or Mild at Screening. The vIGA-AD is evaluated for the entire body except scalp, palms, soles and genitals. Has AD involvement (excluding scalp, palms, soles and genitals) of at least 1.0% BSA and no more than 14.0% BSA. Has at least two target lesions 100 cm2 or greater with a difference no greater than 1 point in lesion TSS and at least 5 cm apart located on the trunk (excluding genitals) or upper extremities (excluding palms). If female, patients with child-bearing potential must have a negative pregnancy test, and agree to practice true abstinence or agree to use highly effective contraception. If male, agree to use a male condom and highly effective contraception with female partners of child-bearing potential. In good health as judged by the Investigator. Exclusion Criteria: Patients who have failed 2 or more prior systemic treatments for AD. Patients who have received a live or attenuated vaccine in the last 12 weeks or intend to receive a live or attenuated vaccine during the study. Patients who cannot discontinue prohibited medications and treatments prior to the Baseline visit and during the study. Has unstable AD, based on the judgement of the Investigator, or any consistent requirement for high potency topical steroids to manage AD signs or symptoms. Patients who have significant active systemic or localized bacterial, viral, fungal, and helminth infection in the last 30 days. Patients unwilling to refrain from prolonged sun exposure or use of a tanning bed or other artificial light emitting devices for 4 weeks prior to Baseline and during the study. Patients with other skin conditions that would interfere with evaluations of the effect of the study medication on AD, as determined by the Investigator. Patients with known genetic dermatological conditions that overlap with AD, such as Netherton syndrome. Previous use of a BTK inhibitor. Women who are pregnant, wishing to become pregnant during the study, or are breastfeeding. Patients currently undergoing allergy (eg, food allergy testing or skin prick testing), patch testing, or food challenges, or plan to do so during the study. Patients who have undergone major surgery within 4 weeks prior to Day 1 or patients who have a major surgery planned during the study. Regular use of drugs of abuse or regular alcohol consumption within 6 months prior to the study.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PRN473 (SAR444727)<br>Multiple topical doses of PRN473 (SAR444727) for 42 days | Drug: PRN473 (SAR444727)<br>* White to off-white gel suspension<br>|
| Placebo Comparator: Placebo<br>Multiple topical doses of placebo for 14 days, and PRN473 (SAR444727) for 28 days | Drug: Placebo<br>* White to off-white gel suspension<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse events (AEs) and serious AEs | Incidence of AEs and SAEs | Until Day 56 | 
| Assessment of local cutaneous tolerability | Incidence and severity of application site events such as burning/stinging, itching, and erythema | Until Day 56 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Plasma PRN473 concentrations |  | Day 1 to Day 43 |