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

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

Status

Completed

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT04992546

Enrollment

Registered

2021-08-05

Start date

2021-08-13

Completion date

2022-12-28

Last updated

2025-09-10

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Atopic Dermatitis

Brief 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.

Detailed description

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

Interventions

DRUGPRN473 (SAR444727)

White to off-white gel suspension

DRUGPlacebo

White to off-white gel suspension

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)

Eligibility

Sex/Gender

ALL

Age

18 Years to 70 Years

Healthy volunteers

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.

Design outcomes

Primary

Measure	Time frame	Description
Percentage of Participants With Application-Site Event During Double-Blind Period	From the first IMP administration (Day 1) up to Week 2	Grading of application-site local tolerability symptoms (burning, pruritus, and erythema) were recorded using the grading scale following each dosing during the double-blind period. Grading of application site tolerability symptoms graded from 0 (none) to 3 (severe).
Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs)	From the first IMP administration (Day 1) up to Day 58	An AE was defined as any untoward medical occurrence in a participant temporally associated with the use of investigational medicinal product (IMP), whether or not considered related to the IMP. SAEs were any untoward medical occurrence that at any dose: resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, was a medically important event. TEAEs were AEs that occurred from the time of the first IMP in the safety analysis period.
Number of Participants With Potentially Clinically Significant Abnormalities (PCSA): Vital Signs	From the first IMP administration (Day 1) up to Day 45	Vital signs assessments included supine systolic blood pressure, supine diastolic blood pressure, supine heart rate (HR), and body temperature. Criteria for PCSA: Supine SBP: ≤ 95 mmHg and decrease from baseline ≥ 20 mmHg, ≥ 160 mmHg and increase from baseline ≥ 20 mmHg; Supine DBP : ≤ 45 mmHg and decrease from baseline ≥ 10 mmHg, ≥ 110 mmHg and increase from baseline ≥ 10 mmHg; Orthostatic SBP: ≤ -20 mmHg; Orthostatic DBP: ≤ -10 mmHg; Supine PR: ≤ 50 beats/min and decrease from baseline ≥ 20 beats/min, ≥ 120 beats/min and increase from baseline ≥ 20 beats/min; Weight :≥ 5% decrease from baseline, ≥ 5% increase from baseline
Number of Participants With PCSA in 12-Lead Electrocardiogram (ECG)	From the first IMP administration (Day 1) up to Day 45	Criteria for PCSA: HR: less than (\<) 50 beats per minute (bpm), \> 90 bpm, \> 90 bpm and increase from baseline \> = 20 bpm, \> 100 bpm; PR interval: \> 200 milliseconds (msec), \> 200 msec and increase from baseline \>= 25 %, \> 220 msec; QRS interval: greater than (\>) 110 msec, \> 110 msec and increase from baseline greater than or equal to (\>=) 25%, \> 120 msec; QT interval: \> 500 msec; QTc interval \> 450 msec; \> 480 msec, increase from baseline (30-60) msec, increase from baseline \> 60 msec.
Number of Participants With PCSA: Hematology	From the first IMP administration (Day 1) up to Day 45	Criteria for PCSA: Hemoglobin (Hb) \<=115 grams per liter (g/L) (Male\[M\]) or \<=95 g/L (Female\[F\]), \>= 185 g/L (M) or \>=165 g/L (F), decrease from baseline \>= 20 g/L; Hematocrit: \<=0.37 volume/volume (v/v) (M) or \<=0.32 v/v (F), \>=0.55 v/v (M) or \>=0.5 v/v (F); Red blood cells (RBC): \>=6 Tera/L; Platelets: \< 100 Giga/L, \>=700 Giga/L; Neutrophils: \<1.5 Giga/L (Non-Black \[NB\]) or \<1.0 Giga/L (Black \[B\]); Lymphocytes: \> 4.0 Giga/L; Monocytes: \>0.7 Giga/L; Basophils: \>0.1 Giga/L; Eosinophils: \>0.5 Giga/L or \>upper limit of normal (ULN) (if ULN \>=0.5 Giga/L).
Number of Participants With PCSA: Electrolyte Parameters	From the first IMP administration (Day 1) up to Day 45	Criteria for PCSA: Sodium: \<=129 millimoles (mmol)/L, \>=160 mmol/L; Potassium: \<3 mmol/L, \>=5.5 mmol/L and Chloride: \<80 mmol/L, \>115 mmol/L.
Number of Participants With PCSA: Metabolic Parameters	From the first IMP administration (Day 1) up to Day 45	Criteria for PCSA: Glucose: \<=3.9 mmol/L and \< lower limit of normal range (LLN); \>=11.1 mmol/L (unfasted \[unfas\]) or \>=7 mmol/L (fasted \[fas\]); Albumin: \<=25 g/L; Creatine kinase (CK): \> 3 ULN, \> 10 ULN; C-Reactive protein: \> 2 ULN or 10 mg(milligram)/L (if ULN not provided).
Number of Participants With PCSA: Renal Function Parameters	From the first IMP administration (Day 1) up to Day 45	Criteria for PCSA: Creatinine: \>=150 micromoles per liter (mcmol/L), \>=30% change from baseline, \>=100% change from baseline.
Number of Participants With PCSA: Liver Function Parameters	From the first IMP administration (Day 1) up to Day 45	Liver function parameters assessments included alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase, lactate dehydrogenase, total bilirubin, direct bilirubin, and gamma glutamyl transferase (GGT).
Number of Participants With PCSA: Urinalysis	From the first IMP administration (Day 1) up to Day 45	Urinalysis parameters assessments included potential of Hydrogen (pH), urobilinogen, and specific gravity.

Secondary

Measure	Time frame	Description
Maximum Plasma Concentration (Cmax) of SAR444727	Day 1, 4 hours post-dose; Day 15, 1 hour post-dose and Day 43, 12 hours post-dose	Plasma samples were collected at indicated timepoints for assessment of SAR444727 concentrations.

Countries

Canada, United States

Participant flow

Recruitment details

The study was conducted at 12 centers in 2 countries. A total of 74 participants were screened from 13 Aug 2021 to 27 Oct 2022, of which 35 were screen failures due to not meeting eligibility criteria.

Pre-assignment details

A total of 39 participants were randomized during the double-blind period and a total of 38 participants entered the open-label period. The study included a 5-week screening period, a 6-week treatment period that included double blinded-period from Days 1 to 14 and an open-label period from Days 15 to 42, end of study/early termination Day 43, and a safety follow-up 2 weeks after the last dose.

Participants by arm

Arm	Count
SAR444727 5% BID+Placebo (Double-blinded Period), Then SAR444727 5% BID (Open Label Period) During the double-blinded period, 2 target lesions per participant (with difference no greater than 1 point in total sign scores \[TSS\]) were randomized in 1:1 ratio to receive either SAR44727 Gel 5 percent (%) or matching placebo in parallel (i.e., each participant was treated with both SAR444727 5% BID and placebo). During open-label period, participants applied SAR444727 Gel, 5% twice daily (BID) to the all atopic dermatitis (AD)-affected areas, except the scalp, palms, soles and genitals through Days 15 to 42.	39
Total	39

Arm

Count

SAR444727 5% BID+Placebo (Double-blinded Period), Then SAR444727 5% BID (Open Label Period)

During the double-blinded period, 2 target lesions per participant (with difference no greater than 1 point in total sign scores \[TSS\]) were randomized in 1:1 ratio to receive either SAR44727 Gel 5 percent (%) or matching placebo in parallel (i.e., each participant was treated with both SAR444727 5% BID and placebo). During open-label period, participants applied SAR444727 Gel, 5% twice daily (BID) to the all atopic dermatitis (AD)-affected areas, except the scalp, palms, soles and genitals through Days 15 to 42.

Total

Withdrawals & dropouts

Period	Reason	FG000
Double-Blinded Treatment Period	Doses missed due to Covid-19 pandemic circumstances at the site	1
Double-Blinded Treatment Period	Withdrawal by Subject	1
Open-Label Treatment Period	Adverse Event	3
Open-Label Treatment Period	Withdrawal by Subject	1

Baseline characteristics

Characteristic	SAR444727 5% BID+Placebo (Double-blinded Period), Then SAR444727 5% BID (Open Label Period)
Age, Continuous	39.8 years STANDARD_DEVIATION 14.2
Race (NIH/OMB) American Indian or Alaska Native	0 Participants
Race (NIH/OMB) Asian	2 Participants
Race (NIH/OMB) Black or African American	12 Participants
Race (NIH/OMB) More than one race	0 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	1 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants
Race (NIH/OMB) White	24 Participants
Sex: Female, Male Female	24 Participants
Sex: Female, Male Male	15 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	0 / 39	0 / 38
other Total, other adverse events	7 / 39	12 / 38
serious Total, serious adverse events	0 / 39	0 / 38

Outcome results

Primary

Number of Participants With PCSA: Electrolyte Parameters

Criteria for PCSA: Sodium: \<=129 millimoles (mmol)/L, \>=160 mmol/L; Potassium: \<3 mmol/L, \>=5.5 mmol/L and Chloride: \<80 mmol/L, \>115 mmol/L.

Time frame: From the first IMP administration (Day 1) up to Day 45

Population: The Safety population included all randomized participants who received any amount of IMP. Only those participants with data available were analyzed. PCSAs were assessed per patient according to study design.

Arm	Measure	Group	Value (COUNT_OF_PARTICIPANTS)
SAR444727 5% BID+Placebo: Double Blinded Period	Number of Participants With PCSA: Electrolyte Parameters	Potassium <3 mmol/L	0 Participants
SAR444727 5% BID+Placebo: Double Blinded Period	Number of Participants With PCSA: Electrolyte Parameters	Potassium >=5.5 mmol/L	1 Participants
SAR444727 5% BID+Placebo: Double Blinded Period	Number of Participants With PCSA: Electrolyte Parameters	Chloride <80 mmol/L	0 Participants
SAR444727 5% BID+Placebo: Double Blinded Period	Number of Participants With PCSA: Electrolyte Parameters	Chloride >115 mmol/L	0 Participants
SAR444727 5% BID+Placebo: Double Blinded Period	Number of Participants With PCSA: Electrolyte Parameters	Sodium <=129 mmol/L	0 Participants
SAR444727 5% BID+Placebo: Double Blinded Period	Number of Participants With PCSA: Electrolyte Parameters	Sodium >=160 mmol/L	0 Participants
SAR444727 5% BID: Open Label Period	Number of Participants With PCSA: Electrolyte Parameters	Sodium <=129 mmol/L	0 Participants
SAR444727 5% BID: Open Label Period	Number of Participants With PCSA: Electrolyte Parameters	Potassium <3 mmol/L	0 Participants
SAR444727 5% BID: Open Label Period	Number of Participants With PCSA: Electrolyte Parameters	Chloride >115 mmol/L	0 Participants
SAR444727 5% BID: Open Label Period	Number of Participants With PCSA: Electrolyte Parameters	Potassium >=5.5 mmol/L	1 Participants
SAR444727 5% BID: Open Label Period	Number of Participants With PCSA: Electrolyte Parameters	Sodium >=160 mmol/L	0 Participants
SAR444727 5% BID: Open Label Period	Number of Participants With PCSA: Electrolyte Parameters	Chloride <80 mmol/L	0 Participants

Primary

Number of Participants With PCSA: Hematology

Criteria for PCSA: Hemoglobin (Hb) \<=115 grams per liter (g/L) (Male\[M\]) or \<=95 g/L (Female\[F\]), \>= 185 g/L (M) or \>=165 g/L (F), decrease from baseline \>= 20 g/L; Hematocrit: \<=0.37 volume/volume (v/v) (M) or \<=0.32 v/v (F), \>=0.55 v/v (M) or \>=0.5 v/v (F); Red blood cells (RBC): \>=6 Tera/L; Platelets: \< 100 Giga/L, \>=700 Giga/L; Neutrophils: \<1.5 Giga/L (Non-Black \[NB\]) or \<1.0 Giga/L (Black \[B\]); Lymphocytes: \> 4.0 Giga/L; Monocytes: \>0.7 Giga/L; Basophils: \>0.1 Giga/L; Eosinophils: \>0.5 Giga/L or \>upper limit of normal (ULN) (if ULN \>=0.5 Giga/L).

Time frame: From the first IMP administration (Day 1) up to Day 45

Arm	Measure	Group	Value (COUNT_OF_PARTICIPANTS)
SAR444727 5% BID+Placebo: Double Blinded Period	Number of Participants With PCSA: Hematology	Hb <= 115 g/L (M); <= 95 g/L (F)	0 Participants
SAR444727 5% BID+Placebo: Double Blinded Period	Number of Participants With PCSA: Hematology	Hb >=185 g/L (M) or >=165 g/L (F)	0 Participants
SAR444727 5% BID+Placebo: Double Blinded Period	Number of Participants With PCSA: Hematology	Hb decrease from baseline >=20 g/L	0 Participants
SAR444727 5% BID+Placebo: Double Blinded Period	Number of Participants With PCSA: Hematology	Hematocrit <=0.37 v/v (M) or <=0.32 v/v (F)	0 Participants
SAR444727 5% BID+Placebo: Double Blinded Period	Number of Participants With PCSA: Hematology	Hematocrit >=0.55 v/v (M) or >=0.5 v/v (F)	0 Participants
SAR444727 5% BID+Placebo: Double Blinded Period	Number of Participants With PCSA: Hematology	RBC >=6 Tera/L	0 Participants
SAR444727 5% BID+Placebo: Double Blinded Period	Number of Participants With PCSA: Hematology	Platelets <100 Giga/L	0 Participants
SAR444727 5% BID+Placebo: Double Blinded Period	Number of Participants With PCSA: Hematology	Platelets >=700 Giga/L	0 Participants
SAR444727 5% BID+Placebo: Double Blinded Period	Number of Participants With PCSA: Hematology	Neutrophils <1.5 Giga/L (NB) or <1.0 Giga/L (B)	0 Participants
SAR444727 5% BID+Placebo: Double Blinded Period	Number of Participants With PCSA: Hematology	Lymphocytes: > 4.0 Giga/L	1 Participants
SAR444727 5% BID+Placebo: Double Blinded Period	Number of Participants With PCSA: Hematology	Monocytes: >0.7 Giga/L	2 Participants
SAR444727 5% BID: Open Label Period	Number of Participants With PCSA: Hematology	RBC >=6 Tera/L	0 Participants
SAR444727 5% BID: Open Label Period	Number of Participants With PCSA: Hematology	Hb <= 115 g/L (M); <= 95 g/L (F)	1 Participants
SAR444727 5% BID: Open Label Period	Number of Participants With PCSA: Hematology	Lymphocytes: > 4.0 Giga/L	2 Participants
SAR444727 5% BID: Open Label Period	Number of Participants With PCSA: Hematology	Hb >=185 g/L (M) or >=165 g/L (F)	0 Participants
SAR444727 5% BID: Open Label Period	Number of Participants With PCSA: Hematology	Monocytes: >0.7 Giga/L	7 Participants
SAR444727 5% BID: Open Label Period	Number of Participants With PCSA: Hematology	Hb decrease from baseline >=20 g/L	0 Participants
SAR444727 5% BID: Open Label Period	Number of Participants With PCSA: Hematology	Platelets <100 Giga/L	0 Participants
SAR444727 5% BID: Open Label Period	Number of Participants With PCSA: Hematology	Hematocrit <=0.37 v/v (M) or <=0.32 v/v (F)	1 Participants
SAR444727 5% BID: Open Label Period	Number of Participants With PCSA: Hematology	Neutrophils <1.5 Giga/L (NB) or <1.0 Giga/L (B)	0 Participants
SAR444727 5% BID: Open Label Period	Number of Participants With PCSA: Hematology	Hematocrit >=0.55 v/v (M) or >=0.5 v/v (F)	0 Participants
SAR444727 5% BID: Open Label Period	Number of Participants With PCSA: Hematology	Platelets >=700 Giga/L	0 Participants

Primary

Number of Participants With PCSA in 12-Lead Electrocardiogram (ECG)

Criteria for PCSA: HR: less than (\<) 50 beats per minute (bpm), \> 90 bpm, \> 90 bpm and increase from baseline \> = 20 bpm, \> 100 bpm; PR interval: \> 200 milliseconds (msec), \> 200 msec and increase from baseline \>= 25 %, \> 220 msec; QRS interval: greater than (\>) 110 msec, \> 110 msec and increase from baseline greater than or equal to (\>=) 25%, \> 120 msec; QT interval: \> 500 msec; QTc interval \> 450 msec; \> 480 msec, increase from baseline (30-60) msec, increase from baseline \> 60 msec.

Time frame: From the first IMP administration (Day 1) up to Day 45

Population: The Safety population included all randomized participants who received any amount of IMP. Only data from the participants analyzed were reported. PCSAs were assessed per patient according to study design.

Arm	Measure	Group	Value (COUNT_OF_PARTICIPANTS)
SAR444727 5% BID+Placebo: Double Blinded Period	Number of Participants With PCSA in 12-Lead Electrocardiogram (ECG)	HR < 50 bpm	0 Participants
SAR444727 5% BID+Placebo: Double Blinded Period	Number of Participants With PCSA in 12-Lead Electrocardiogram (ECG)	HR > 90 bpm	1 Participants
SAR444727 5% BID+Placebo: Double Blinded Period	Number of Participants With PCSA in 12-Lead Electrocardiogram (ECG)	HR > 90 bpm and increase from baseline >= 20 bpm	0 Participants
SAR444727 5% BID+Placebo: Double Blinded Period	Number of Participants With PCSA in 12-Lead Electrocardiogram (ECG)	HR > 100 bpm	0 Participants
SAR444727 5% BID+Placebo: Double Blinded Period	Number of Participants With PCSA in 12-Lead Electrocardiogram (ECG)	QTc interval > 480 msec	0 Participants
SAR444727 5% BID+Placebo: Double Blinded Period	Number of Participants With PCSA in 12-Lead Electrocardiogram (ECG)	QTc interval increase from baseline (30-60) msec	2 Participants
SAR444727 5% BID+Placebo: Double Blinded Period	Number of Participants With PCSA in 12-Lead Electrocardiogram (ECG)	QTc interval increase from baseline > 60 msec	0 Participants
SAR444727 5% BID+Placebo: Double Blinded Period	Number of Participants With PCSA in 12-Lead Electrocardiogram (ECG)	PR interval > 200 msec	1 Participants
SAR444727 5% BID+Placebo: Double Blinded Period	Number of Participants With PCSA in 12-Lead Electrocardiogram (ECG)	PR interval > 200 msec and increase from baseline >= 25%	0 Participants
SAR444727 5% BID+Placebo: Double Blinded Period	Number of Participants With PCSA in 12-Lead Electrocardiogram (ECG)	PR interval > 220 msec	0 Participants
SAR444727 5% BID+Placebo: Double Blinded Period	Number of Participants With PCSA in 12-Lead Electrocardiogram (ECG)	QRS interval > 110 msec	2 Participants
SAR444727 5% BID+Placebo: Double Blinded Period	Number of Participants With PCSA in 12-Lead Electrocardiogram (ECG)	QRS interval > 110 msec and increase from baseline >= 25%	0 Participants
SAR444727 5% BID+Placebo: Double Blinded Period	Number of Participants With PCSA in 12-Lead Electrocardiogram (ECG)	QRS interval > 120 msec	0 Participants
SAR444727 5% BID+Placebo: Double Blinded Period	Number of Participants With PCSA in 12-Lead Electrocardiogram (ECG)	QT interval > 500 msec	0 Participants
SAR444727 5% BID+Placebo: Double Blinded Period	Number of Participants With PCSA in 12-Lead Electrocardiogram (ECG)	QTc interval > 450 msec	1 Participants

Primary

Number of Participants With PCSA: Liver Function Parameters

Liver function parameters assessments included alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase, lactate dehydrogenase, total bilirubin, direct bilirubin, and gamma glutamyl transferase (GGT).

Time frame: From the first IMP administration (Day 1) up to Day 45

Population: The Safety population included all randomized participants who received any amount of IMP. PCSAs were assessed per patient according to study design.

Arm	Measure	Group	Value (COUNT_OF_PARTICIPANTS)
SAR444727 5% BID+Placebo: Double Blinded Period	Number of Participants With PCSA: Liver Function Parameters	ALT	0 Participants
SAR444727 5% BID+Placebo: Double Blinded Period	Number of Participants With PCSA: Liver Function Parameters	Alkaline phosphatase	0 Participants
SAR444727 5% BID+Placebo: Double Blinded Period	Number of Participants With PCSA: Liver Function Parameters	GGT	0 Participants
SAR444727 5% BID+Placebo: Double Blinded Period	Number of Participants With PCSA: Liver Function Parameters	Lactate dehydrogenase	0 Participants
SAR444727 5% BID+Placebo: Double Blinded Period	Number of Participants With PCSA: Liver Function Parameters	AST	0 Participants
SAR444727 5% BID+Placebo: Double Blinded Period	Number of Participants With PCSA: Liver Function Parameters	Total bilirubin	0 Participants
SAR444727 5% BID+Placebo: Double Blinded Period	Number of Participants With PCSA: Liver Function Parameters	Direct bilirubin	0 Participants
SAR444727 5% BID: Open Label Period	Number of Participants With PCSA: Liver Function Parameters	Total bilirubin	0 Participants
SAR444727 5% BID: Open Label Period	Number of Participants With PCSA: Liver Function Parameters	Direct bilirubin	0 Participants
SAR444727 5% BID: Open Label Period	Number of Participants With PCSA: Liver Function Parameters	GGT	0 Participants
SAR444727 5% BID: Open Label Period	Number of Participants With PCSA: Liver Function Parameters	ALT	0 Participants
SAR444727 5% BID: Open Label Period	Number of Participants With PCSA: Liver Function Parameters	AST	0 Participants
SAR444727 5% BID: Open Label Period	Number of Participants With PCSA: Liver Function Parameters	Alkaline phosphatase	0 Participants
SAR444727 5% BID: Open Label Period	Number of Participants With PCSA: Liver Function Parameters	Lactate dehydrogenase	0 Participants

Primary

Number of Participants With PCSA: Metabolic Parameters

Criteria for PCSA: Glucose: \<=3.9 mmol/L and \< lower limit of normal range (LLN); \>=11.1 mmol/L (unfasted \[unfas\]) or \>=7 mmol/L (fasted \[fas\]); Albumin: \<=25 g/L; Creatine kinase (CK): \> 3 ULN, \> 10 ULN; C-Reactive protein: \> 2 ULN or 10 mg(milligram)/L (if ULN not provided).

Time frame: From the first IMP administration (Day 1) up to Day 45

Arm	Measure	Group	Value (COUNT_OF_PARTICIPANTS)
SAR444727 5% BID+Placebo: Double Blinded Period	Number of Participants With PCSA: Metabolic Parameters	Glucose <=3.9 mmol/L and <LLN	0 Participants
SAR444727 5% BID+Placebo: Double Blinded Period	Number of Participants With PCSA: Metabolic Parameters	Glucose >=11.1 mmol/L (unfas) or >=7 mmol/L (fas)	2 Participants
SAR444727 5% BID+Placebo: Double Blinded Period	Number of Participants With PCSA: Metabolic Parameters	Albumin <=25 g/L	0 Participants
SAR444727 5% BID+Placebo: Double Blinded Period	Number of Participants With PCSA: Metabolic Parameters	C-Reactive protein: > 2 ULN or 10 mg/L (if ULN not provided)	1 Participants
SAR444727 5% BID+Placebo: Double Blinded Period	Number of Participants With PCSA: Metabolic Parameters	CK > 3 ULN	1 Participants
SAR444727 5% BID+Placebo: Double Blinded Period	Number of Participants With PCSA: Metabolic Parameters	CK > 10 ULN	1 Participants
SAR444727 5% BID: Open Label Period	Number of Participants With PCSA: Metabolic Parameters	CK > 3 ULN	0 Participants
SAR444727 5% BID: Open Label Period	Number of Participants With PCSA: Metabolic Parameters	Glucose <=3.9 mmol/L and <LLN	0 Participants
SAR444727 5% BID: Open Label Period	Number of Participants With PCSA: Metabolic Parameters	C-Reactive protein: > 2 ULN or 10 mg/L (if ULN not provided)	5 Participants
SAR444727 5% BID: Open Label Period	Number of Participants With PCSA: Metabolic Parameters	Glucose >=11.1 mmol/L (unfas) or >=7 mmol/L (fas)	4 Participants
SAR444727 5% BID: Open Label Period	Number of Participants With PCSA: Metabolic Parameters	CK > 10 ULN	0 Participants
SAR444727 5% BID: Open Label Period	Number of Participants With PCSA: Metabolic Parameters	Albumin <=25 g/L	0 Participants

Primary

Number of Participants With PCSA: Renal Function Parameters

Criteria for PCSA: Creatinine: \>=150 micromoles per liter (mcmol/L), \>=30% change from baseline, \>=100% change from baseline.

Time frame: From the first IMP administration (Day 1) up to Day 45

Population: The safety population included all randomized participants who received any amount of IMP. Only those participants with data available were analyzed. PCSAs were assessed per patient according to study design.

Arm	Measure	Group	Value (COUNT_OF_PARTICIPANTS)
SAR444727 5% BID+Placebo: Double Blinded Period	Number of Participants With PCSA: Renal Function Parameters	Creatinine >=150 mcmol/L	0 Participants
SAR444727 5% BID+Placebo: Double Blinded Period	Number of Participants With PCSA: Renal Function Parameters	Creatinine >=30% change from baseline	1 Participants
SAR444727 5% BID+Placebo: Double Blinded Period	Number of Participants With PCSA: Renal Function Parameters	Creatinine >=100% change from baseline	0 Participants
SAR444727 5% BID: Open Label Period	Number of Participants With PCSA: Renal Function Parameters	Creatinine >=150 mcmol/L	0 Participants
SAR444727 5% BID: Open Label Period	Number of Participants With PCSA: Renal Function Parameters	Creatinine >=30% change from baseline	3 Participants
SAR444727 5% BID: Open Label Period	Number of Participants With PCSA: Renal Function Parameters	Creatinine >=100% change from baseline	0 Participants

Primary

Number of Participants With PCSA: Urinalysis

Urinalysis parameters assessments included potential of Hydrogen (pH), urobilinogen, and specific gravity.

Time frame: From the first IMP administration (Day 1) up to Day 45

Population: The Safety population included all randomized participants who received any amount of IMP. PCSAs were assessed per patient according to study design.

Arm	Measure	Group	Value (COUNT_OF_PARTICIPANTS)
SAR444727 5% BID+Placebo: Double Blinded Period	Number of Participants With PCSA: Urinalysis	pH	0 Participants
SAR444727 5% BID+Placebo: Double Blinded Period	Number of Participants With PCSA: Urinalysis	Urobilinogen	0 Participants
SAR444727 5% BID+Placebo: Double Blinded Period	Number of Participants With PCSA: Urinalysis	Specific gravity	0 Participants
SAR444727 5% BID: Open Label Period	Number of Participants With PCSA: Urinalysis	pH	0 Participants
SAR444727 5% BID: Open Label Period	Number of Participants With PCSA: Urinalysis	Urobilinogen	0 Participants
SAR444727 5% BID: Open Label Period	Number of Participants With PCSA: Urinalysis	Specific gravity	0 Participants

Primary

Number of Participants With Potentially Clinically Significant Abnormalities (PCSA): Vital Signs

Vital signs assessments included supine systolic blood pressure, supine diastolic blood pressure, supine heart rate (HR), and body temperature. Criteria for PCSA: Supine SBP: ≤ 95 mmHg and decrease from baseline ≥ 20 mmHg, ≥ 160 mmHg and increase from baseline ≥ 20 mmHg; Supine DBP : ≤ 45 mmHg and decrease from baseline ≥ 10 mmHg, ≥ 110 mmHg and increase from baseline ≥ 10 mmHg; Orthostatic SBP: ≤ -20 mmHg; Orthostatic DBP: ≤ -10 mmHg; Supine PR: ≤ 50 beats/min and decrease from baseline ≥ 20 beats/min, ≥ 120 beats/min and increase from baseline ≥ 20 beats/min; Weight :≥ 5% decrease from baseline, ≥ 5% increase from baseline

Time frame: From the first IMP administration (Day 1) up to Day 45

Arm	Measure	Group	Value (COUNT_OF_PARTICIPANTS)
SAR444727 5% BID+Placebo: Double Blinded Period	Number of Participants With Potentially Clinically Significant Abnormalities (PCSA): Vital Signs	Supine systolic blood pressure	0 Participants
SAR444727 5% BID+Placebo: Double Blinded Period	Number of Participants With Potentially Clinically Significant Abnormalities (PCSA): Vital Signs	Supine diastolic blood pressure	0 Participants
SAR444727 5% BID+Placebo: Double Blinded Period	Number of Participants With Potentially Clinically Significant Abnormalities (PCSA): Vital Signs	Supine HR	0 Participants
SAR444727 5% BID+Placebo: Double Blinded Period	Number of Participants With Potentially Clinically Significant Abnormalities (PCSA): Vital Signs	Body temperature	0 Participants

Primary

Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs)

An AE was defined as any untoward medical occurrence in a participant temporally associated with the use of investigational medicinal product (IMP), whether or not considered related to the IMP. SAEs were any untoward medical occurrence that at any dose: resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, was a medically important event. TEAEs were AEs that occurred from the time of the first IMP in the safety analysis period.

Time frame: From the first IMP administration (Day 1) up to Day 58

Population: The Safety population included all randomized participants who received any amount of IMP. TEAE and TESAE were assessed per patient according to study design.

Arm	Measure	Group	Value (COUNT_OF_PARTICIPANTS)
SAR444727 5% BID+Placebo: Double Blinded Period	Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs)	TEAEs	7 Participants
SAR444727 5% BID+Placebo: Double Blinded Period	Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs)	TESAEs	0 Participants
SAR444727 5% BID: Open Label Period	Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs)	TEAEs	12 Participants
SAR444727 5% BID: Open Label Period	Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs)	TESAEs	0 Participants

Primary

Percentage of Participants With Application-Site Event During Double-Blind Period

Grading of application-site local tolerability symptoms (burning, pruritus, and erythema) were recorded using the grading scale following each dosing during the double-blind period. Grading of application site tolerability symptoms graded from 0 (none) to 3 (severe).

Time frame: From the first IMP administration (Day 1) up to Week 2

Population: The Safety population included all randomized participants who received any amount of IMP.

Arm	Measure	Group	Value (NUMBER)
SAR444727 5% BID+Placebo: Double Blinded Period	Percentage of Participants With Application-Site Event During Double-Blind Period	Burning	23.7 percentage of participants
SAR444727 5% BID+Placebo: Double Blinded Period	Percentage of Participants With Application-Site Event During Double-Blind Period	Pruritus	31.6 percentage of participants
SAR444727 5% BID+Placebo: Double Blinded Period	Percentage of Participants With Application-Site Event During Double-Blind Period	Erythema	47.4 percentage of participants
SAR444727 5% BID: Open Label Period	Percentage of Participants With Application-Site Event During Double-Blind Period	Burning	17.9 percentage of participants
SAR444727 5% BID: Open Label Period	Percentage of Participants With Application-Site Event During Double-Blind Period	Pruritus	25.6 percentage of participants
SAR444727 5% BID: Open Label Period	Percentage of Participants With Application-Site Event During Double-Blind Period	Erythema	48.7 percentage of participants

Secondary

Maximum Plasma Concentration (Cmax) of SAR444727

Plasma samples were collected at indicated timepoints for assessment of SAR444727 concentrations.

Time frame: Day 1, 4 hours post-dose; Day 15, 1 hour post-dose and Day 43, 12 hours post-dose

Population: The Pharmacokinetic (PK) population included all participants who received any amount of IMP and had at least 1 PK sample. Only those participants with data available were analyzed.

Arm	Measure	Group	Value (MEAN)	Dispersion
SAR444727 5% BID+Placebo: Double Blinded Period	Maximum Plasma Concentration (Cmax) of SAR444727	Day 1, 4 hours post-dose	0 nanogram/milliliter	Standard Deviation 0.096
SAR444727 5% BID+Placebo: Double Blinded Period	Maximum Plasma Concentration (Cmax) of SAR444727	Day 15, 1 hour post-dose	0 nanogram/milliliter	Standard Deviation 0.152
SAR444727 5% BID+Placebo: Double Blinded Period	Maximum Plasma Concentration (Cmax) of SAR444727	Day 43, 12 hours post-dose	0 nanogram/milliliter	Standard Deviation 0.035

Source: ClinicalTrials.gov · Data processed: Feb 4, 2026

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

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Outcome results

Number of Participants With PCSA: Electrolyte Parameters

Number of Participants With PCSA: Hematology

Number of Participants With PCSA in 12-Lead Electrocardiogram (ECG)

Number of Participants With PCSA: Liver Function Parameters

Number of Participants With PCSA: Metabolic Parameters

Number of Participants With PCSA: Renal Function Parameters

Number of Participants With PCSA: Urinalysis

Number of Participants With Potentially Clinically Significant Abnormalities (PCSA): Vital Signs

Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs)

Percentage of Participants With Application-Site Event During Double-Blind Period

Maximum Plasma Concentration (Cmax) of SAR444727