phase 2a study of the safety, tolerability, and pharmacokinetics of topically administered prn473 (sar444727) in patients with mild to moderate atopic dermatitis

Conditions: Atopic Dermatitis

Summary: this was 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) were randomly assigned to treatment in an intra-patient 1:1 manner, one lesion to prn473 and the other to matching placebo. participation took 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.

study duration per patient was approximately 56 days including a 42-days treatment period.

Eligibility criteria:
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 was evaluated for the entire body except scalp, palms, soles and genitals. * hadad involvement (excluding scalp, palms, soles and genitals) of at least 1.0% bsa and no more than 14.0% bsa. * had 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 had failed 2 or more prior systemic treatments for ad. * patients who had 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 had 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 used of a btk inhibitor. * women who were pregnant, wishing to become pregnant during the study, or were breastfeeding. * patients were 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 had undergone major surgery within 4 weeks prior to day 1 or patients who had a major surgery planned during the study. * regular use of drugs of abuse or regular alcohol consumption within 6 months prior to the study.