Trial Outcomes & Findings for Phase 2a Study of the Safety, Tolerability, and Pharmacokinetics of Topically Administered PRN473 (SAR444727) in Patients With Mild to Moderate Atopic Dermatitis (NCT NCT04992546)

NCT ID: NCT04992546

Last Updated: 2025-09-10

Results Overview

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.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 39 participants
• Primary outcome timeframe: From the first IMP administration (Day 1) up to Day 58
• Results posted on: 2025-09-10

Participant Flow

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.

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.

Unit of analysis: lession

Participant milestones

Measure	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.
Double-Blinded Treatment Period STARTED	39 78
Double-Blinded Treatment Period COMPLETED	37 74
Double-Blinded Treatment Period NOT COMPLETED	2 4
Open-Label Treatment Period STARTED	38 76
Open-Label Treatment Period COMPLETED	34 68
Open-Label Treatment Period NOT COMPLETED	4 8

Reasons for withdrawal

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

Baseline Characteristics

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

Baseline characteristics by cohort

Measure	SAR444727 5% BID+Placebo (Double-blinded Period), Then SAR444727 5% BID (Open Label Period) n=39 Participants 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.
Age, Continuous	39.8 years STANDARD_DEVIATION 14.2 • n=5 Participants
Sex: Female, Male Female	24 Participants n=5 Participants
Sex: Female, Male Male	15 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	2 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	1 Participants n=5 Participants
Race (NIH/OMB) Black or African American	12 Participants n=5 Participants
Race (NIH/OMB) White	24 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants

PRIMARY outcome

Timeframe: 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.

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.

Outcome measures

Measure	SAR444727 5% BID+Placebo: Double Blinded Period n=39 Participants During the double-blinded period, 2 target lesions per participant (with difference no greater than 1 point in TSS) were randomized in 1:1 ratio to receive either SAR44727 Gel 5% or matching placebo (i.e., each participant was treated with both SAR444727 5% BID and placebo in parallel). This group represents the AE which occurred while participants were treated with both SAR444727 5% BID and placebo at the same time.	SAR444727 5% BID: Open Label Period n=38 Participants During open-label period, participants applied SAR444727 Gel, 5% BID to the all AD-affected areas, except the scalp, palms, soles and genitals through Days 15 to 42.
Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) TEAEs	7 Participants	12 Participants
Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) TESAEs	0 Participants	0 Participants

PRIMARY outcome

Timeframe: 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.

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

Outcome measures

Measure	SAR444727 5% BID+Placebo: Double Blinded Period n=38 Participants During the double-blinded period, 2 target lesions per participant (with difference no greater than 1 point in TSS) were randomized in 1:1 ratio to receive either SAR44727 Gel 5% or matching placebo (i.e., each participant was treated with both SAR444727 5% BID and placebo in parallel). This group represents the AE which occurred while participants were treated with both SAR444727 5% BID and placebo at the same time.	SAR444727 5% BID: Open Label Period During open-label period, participants applied SAR444727 Gel, 5% BID to the all AD-affected areas, except the scalp, palms, soles and genitals through Days 15 to 42.
Number of Participants With Potentially Clinically Significant Abnormalities (PCSA): Vital Signs Supine systolic blood pressure	0 Participants	—
Number of Participants With Potentially Clinically Significant Abnormalities (PCSA): Vital Signs Supine diastolic blood pressure	0 Participants	—
Number of Participants With Potentially Clinically Significant Abnormalities (PCSA): Vital Signs Supine HR	0 Participants	—
Number of Participants With Potentially Clinically Significant Abnormalities (PCSA): Vital Signs Body temperature	0 Participants	—

PRIMARY outcome

Timeframe: 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.

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.

Outcome measures

Measure	SAR444727 5% BID+Placebo: Double Blinded Period n=38 Participants During the double-blinded period, 2 target lesions per participant (with difference no greater than 1 point in TSS) were randomized in 1:1 ratio to receive either SAR44727 Gel 5% or matching placebo (i.e., each participant was treated with both SAR444727 5% BID and placebo in parallel). This group represents the AE which occurred while participants were treated with both SAR444727 5% BID and placebo at the same time.	SAR444727 5% BID: Open Label Period During open-label period, participants applied SAR444727 Gel, 5% BID to the all AD-affected areas, except the scalp, palms, soles and genitals through Days 15 to 42.
Number of Participants With PCSA in 12-Lead Electrocardiogram (ECG) HR < 50 bpm	0 Participants	—
Number of Participants With PCSA in 12-Lead Electrocardiogram (ECG) HR > 90 bpm	1 Participants	—
Number of Participants With PCSA in 12-Lead Electrocardiogram (ECG) HR > 90 bpm and increase from baseline >= 20 bpm	0 Participants	—
Number of Participants With PCSA in 12-Lead Electrocardiogram (ECG) HR > 100 bpm	0 Participants	—
Number of Participants With PCSA in 12-Lead Electrocardiogram (ECG) PR interval > 200 msec	1 Participants	—
Number of Participants With PCSA in 12-Lead Electrocardiogram (ECG) PR interval > 200 msec and increase from baseline >= 25%	0 Participants	—
Number of Participants With PCSA in 12-Lead Electrocardiogram (ECG) PR interval > 220 msec	0 Participants	—
Number of Participants With PCSA in 12-Lead Electrocardiogram (ECG) QRS interval > 110 msec	2 Participants	—
Number of Participants With PCSA in 12-Lead Electrocardiogram (ECG) QRS interval > 110 msec and increase from baseline >= 25%	0 Participants	—
Number of Participants With PCSA in 12-Lead Electrocardiogram (ECG) QRS interval > 120 msec	0 Participants	—
Number of Participants With PCSA in 12-Lead Electrocardiogram (ECG) QT interval > 500 msec	0 Participants	—
Number of Participants With PCSA in 12-Lead Electrocardiogram (ECG) QTc interval > 450 msec	1 Participants	—
Number of Participants With PCSA in 12-Lead Electrocardiogram (ECG) QTc interval > 480 msec	0 Participants	—
Number of Participants With PCSA in 12-Lead Electrocardiogram (ECG) QTc interval increase from baseline (30-60) msec	2 Participants	—
Number of Participants With PCSA in 12-Lead Electrocardiogram (ECG) QTc interval increase from baseline > 60 msec	0 Participants	—

PRIMARY outcome

Timeframe: 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.

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).

Outcome measures

Measure	SAR444727 5% BID+Placebo: Double Blinded Period n=24 Participants During the double-blinded period, 2 target lesions per participant (with difference no greater than 1 point in TSS) were randomized in 1:1 ratio to receive either SAR44727 Gel 5% or matching placebo (i.e., each participant was treated with both SAR444727 5% BID and placebo in parallel). This group represents the AE which occurred while participants were treated with both SAR444727 5% BID and placebo at the same time.	SAR444727 5% BID: Open Label Period n=38 Participants During open-label period, participants applied SAR444727 Gel, 5% BID to the all AD-affected areas, except the scalp, palms, soles and genitals through Days 15 to 42.
Number of Participants With PCSA: Hematology Hb <= 115 g/L (M); <= 95 g/L (F)	0 Participants	1 Participants
Number of Participants With PCSA: Hematology Hb >=185 g/L (M) or >=165 g/L (F)	0 Participants	0 Participants
Number of Participants With PCSA: Hematology Hb decrease from baseline >=20 g/L	0 Participants	0 Participants
Number of Participants With PCSA: Hematology Hematocrit <=0.37 v/v (M) or <=0.32 v/v (F)	0 Participants	1 Participants
Number of Participants With PCSA: Hematology Hematocrit >=0.55 v/v (M) or >=0.5 v/v (F)	0 Participants	0 Participants
Number of Participants With PCSA: Hematology RBC >=6 Tera/L	0 Participants	0 Participants
Number of Participants With PCSA: Hematology Platelets <100 Giga/L	0 Participants	0 Participants
Number of Participants With PCSA: Hematology Platelets >=700 Giga/L	0 Participants	0 Participants
Number of Participants With PCSA: Hematology Neutrophils <1.5 Giga/L (NB) or <1.0 Giga/L (B)	0 Participants	0 Participants
Number of Participants With PCSA: Hematology Lymphocytes: > 4.0 Giga/L	1 Participants	2 Participants
Number of Participants With PCSA: Hematology Monocytes: >0.7 Giga/L	2 Participants	7 Participants

PRIMARY outcome

Timeframe: 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.

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.

Outcome measures

Measure	SAR444727 5% BID+Placebo: Double Blinded Period n=24 Participants During the double-blinded period, 2 target lesions per participant (with difference no greater than 1 point in TSS) were randomized in 1:1 ratio to receive either SAR44727 Gel 5% or matching placebo (i.e., each participant was treated with both SAR444727 5% BID and placebo in parallel). This group represents the AE which occurred while participants were treated with both SAR444727 5% BID and placebo at the same time.	SAR444727 5% BID: Open Label Period n=38 Participants During open-label period, participants applied SAR444727 Gel, 5% BID to the all AD-affected areas, except the scalp, palms, soles and genitals through Days 15 to 42.
Number of Participants With PCSA: Electrolyte Parameters Sodium <=129 mmol/L	0 Participants	0 Participants
Number of Participants With PCSA: Electrolyte Parameters Sodium >=160 mmol/L	0 Participants	0 Participants
Number of Participants With PCSA: Electrolyte Parameters Potassium <3 mmol/L	0 Participants	0 Participants
Number of Participants With PCSA: Electrolyte Parameters Potassium >=5.5 mmol/L	1 Participants	1 Participants
Number of Participants With PCSA: Electrolyte Parameters Chloride <80 mmol/L	0 Participants	0 Participants
Number of Participants With PCSA: Electrolyte Parameters Chloride >115 mmol/L	0 Participants	0 Participants

PRIMARY outcome

Timeframe: 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.

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).

Outcome measures

Measure	SAR444727 5% BID+Placebo: Double Blinded Period n=24 Participants During the double-blinded period, 2 target lesions per participant (with difference no greater than 1 point in TSS) were randomized in 1:1 ratio to receive either SAR44727 Gel 5% or matching placebo (i.e., each participant was treated with both SAR444727 5% BID and placebo in parallel). This group represents the AE which occurred while participants were treated with both SAR444727 5% BID and placebo at the same time.	SAR444727 5% BID: Open Label Period n=38 Participants During open-label period, participants applied SAR444727 Gel, 5% BID to the all AD-affected areas, except the scalp, palms, soles and genitals through Days 15 to 42.
Number of Participants With PCSA: Metabolic Parameters Glucose <=3.9 mmol/L and <LLN	0 Participants	0 Participants
Number of Participants With PCSA: Metabolic Parameters Glucose >=11.1 mmol/L (unfas) or >=7 mmol/L (fas)	2 Participants	4 Participants
Number of Participants With PCSA: Metabolic Parameters Albumin <=25 g/L	0 Participants	0 Participants
Number of Participants With PCSA: Metabolic Parameters CK > 3 ULN	1 Participants	0 Participants
Number of Participants With PCSA: Metabolic Parameters CK > 10 ULN	1 Participants	0 Participants
Number of Participants With PCSA: Metabolic Parameters C-Reactive protein: > 2 ULN or 10 mg/L (if ULN not provided)	1 Participants	5 Participants

PRIMARY outcome

Timeframe: 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.

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

Outcome measures

Measure	SAR444727 5% BID+Placebo: Double Blinded Period n=24 Participants During the double-blinded period, 2 target lesions per participant (with difference no greater than 1 point in TSS) were randomized in 1:1 ratio to receive either SAR44727 Gel 5% or matching placebo (i.e., each participant was treated with both SAR444727 5% BID and placebo in parallel). This group represents the AE which occurred while participants were treated with both SAR444727 5% BID and placebo at the same time.	SAR444727 5% BID: Open Label Period n=38 Participants During open-label period, participants applied SAR444727 Gel, 5% BID to the all AD-affected areas, except the scalp, palms, soles and genitals through Days 15 to 42.
Number of Participants With PCSA: Renal Function Parameters Creatinine >=150 mcmol/L	0 Participants	0 Participants
Number of Participants With PCSA: Renal Function Parameters Creatinine >=30% change from baseline	1 Participants	3 Participants
Number of Participants With PCSA: Renal Function Parameters Creatinine >=100% change from baseline	0 Participants	0 Participants

PRIMARY outcome

Timeframe: 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.

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

Outcome measures

Measure	SAR444727 5% BID+Placebo: Double Blinded Period n=39 Participants During the double-blinded period, 2 target lesions per participant (with difference no greater than 1 point in TSS) were randomized in 1:1 ratio to receive either SAR44727 Gel 5% or matching placebo (i.e., each participant was treated with both SAR444727 5% BID and placebo in parallel). This group represents the AE which occurred while participants were treated with both SAR444727 5% BID and placebo at the same time.	SAR444727 5% BID: Open Label Period n=38 Participants During open-label period, participants applied SAR444727 Gel, 5% BID to the all AD-affected areas, except the scalp, palms, soles and genitals through Days 15 to 42.
Number of Participants With PCSA: Liver Function Parameters ALT	0 Participants	0 Participants
Number of Participants With PCSA: Liver Function Parameters AST	0 Participants	0 Participants
Number of Participants With PCSA: Liver Function Parameters Alkaline phosphatase	0 Participants	0 Participants
Number of Participants With PCSA: Liver Function Parameters Lactate dehydrogenase	0 Participants	0 Participants
Number of Participants With PCSA: Liver Function Parameters Total bilirubin	0 Participants	0 Participants
Number of Participants With PCSA: Liver Function Parameters Direct bilirubin	0 Participants	0 Participants
Number of Participants With PCSA: Liver Function Parameters GGT	0 Participants	0 Participants

PRIMARY outcome

Timeframe: 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.

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

Outcome measures

Measure	SAR444727 5% BID+Placebo: Double Blinded Period n=39 Participants During the double-blinded period, 2 target lesions per participant (with difference no greater than 1 point in TSS) were randomized in 1:1 ratio to receive either SAR44727 Gel 5% or matching placebo (i.e., each participant was treated with both SAR444727 5% BID and placebo in parallel). This group represents the AE which occurred while participants were treated with both SAR444727 5% BID and placebo at the same time.	SAR444727 5% BID: Open Label Period n=38 Participants During open-label period, participants applied SAR444727 Gel, 5% BID to the all AD-affected areas, except the scalp, palms, soles and genitals through Days 15 to 42.
Number of Participants With PCSA: Urinalysis pH	0 Participants	0 Participants
Number of Participants With PCSA: Urinalysis Urobilinogen	0 Participants	0 Participants
Number of Participants With PCSA: Urinalysis Specific gravity	0 Participants	0 Participants

PRIMARY outcome

Timeframe: 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.

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).

Outcome measures

Measure	SAR444727 5% BID+Placebo: Double Blinded Period n=38 Participants During the double-blinded period, 2 target lesions per participant (with difference no greater than 1 point in TSS) were randomized in 1:1 ratio to receive either SAR44727 Gel 5% or matching placebo (i.e., each participant was treated with both SAR444727 5% BID and placebo in parallel). This group represents the AE which occurred while participants were treated with both SAR444727 5% BID and placebo at the same time.	SAR444727 5% BID: Open Label Period n=39 Participants During open-label period, participants applied SAR444727 Gel, 5% BID to the all AD-affected areas, except the scalp, palms, soles and genitals through Days 15 to 42.
Percentage of Participants With Application-Site Event During Double-Blind Period Burning	23.7 percentage of participants	17.9 percentage of participants
Percentage of Participants With Application-Site Event During Double-Blind Period Pruritus	31.6 percentage of participants	25.6 percentage of participants
Percentage of Participants With Application-Site Event During Double-Blind Period Erythema	47.4 percentage of participants	48.7 percentage of participants

SECONDARY outcome

Timeframe: 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.

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

Outcome measures

Measure	SAR444727 5% BID+Placebo: Double Blinded Period n=36 Participants During the double-blinded period, 2 target lesions per participant (with difference no greater than 1 point in TSS) were randomized in 1:1 ratio to receive either SAR44727 Gel 5% or matching placebo (i.e., each participant was treated with both SAR444727 5% BID and placebo in parallel). This group represents the AE which occurred while participants were treated with both SAR444727 5% BID and placebo at the same time.	SAR444727 5% BID: Open Label Period During open-label period, participants applied SAR444727 Gel, 5% BID to the all AD-affected areas, except the scalp, palms, soles and genitals through Days 15 to 42.
Maximum Plasma Concentration (Cmax) of SAR444727 Day 1, 4 hours post-dose	0 nanogram/milliliter Standard Deviation 0.096	—
Maximum Plasma Concentration (Cmax) of SAR444727 Day 15, 1 hour post-dose	0 nanogram/milliliter Standard Deviation 0.152	—
Maximum Plasma Concentration (Cmax) of SAR444727 Day 43, 12 hours post-dose	0 nanogram/milliliter Standard Deviation 0.035	—

Adverse Events

SAR444727 5% BID+Placebo: Double Blinded Period

Serious events: 0 serious events

Other events: 7 other events

Deaths: 0 deaths

SAR444727 5% BID: Open Label Period

Serious events: 0 serious events

Other events: 12 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	SAR444727 5% BID+Placebo: Double Blinded Period n=39 participants at risk 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 (i.e., each participant was treated with both SAR444727 5% BID and placebo in parallel). This group represents the AE which occurred while participants were treated with both SAR444727 5% BID and placebo at the same time.	SAR444727 5% BID: Open Label Period n=38 participants at risk During open-label period, participants applied SAR444727 Gel, 5% BID to the all AD-affected areas, except the scalp, palms, soles and genitals through Days 15 to 42.
Infections and infestations Bronchitis	0.00% 0/39 • TEAE data was collected from the first IMP administration (Day 1) up to Day 58 Analysis was performed on the safety population. As is pre-specified in the study protocol, all adverse events were collected at the participant level.	2.6% 1/38 • Number of events 1 • TEAE data was collected from the first IMP administration (Day 1) up to Day 58 Analysis was performed on the safety population. As is pre-specified in the study protocol, all adverse events were collected at the participant level.
Infections and infestations Gastroenteritis viral	0.00% 0/39 • TEAE data was collected from the first IMP administration (Day 1) up to Day 58 Analysis was performed on the safety population. As is pre-specified in the study protocol, all adverse events were collected at the participant level.	2.6% 1/38 • Number of events 1 • TEAE data was collected from the first IMP administration (Day 1) up to Day 58 Analysis was performed on the safety population. As is pre-specified in the study protocol, all adverse events were collected at the participant level.
Infections and infestations Mastitis	0.00% 0/39 • TEAE data was collected from the first IMP administration (Day 1) up to Day 58 Analysis was performed on the safety population. As is pre-specified in the study protocol, all adverse events were collected at the participant level.	2.6% 1/38 • Number of events 1 • TEAE data was collected from the first IMP administration (Day 1) up to Day 58 Analysis was performed on the safety population. As is pre-specified in the study protocol, all adverse events were collected at the participant level.
Infections and infestations Pharyngitis streptococcal	0.00% 0/39 • TEAE data was collected from the first IMP administration (Day 1) up to Day 58 Analysis was performed on the safety population. As is pre-specified in the study protocol, all adverse events were collected at the participant level.	2.6% 1/38 • Number of events 1 • TEAE data was collected from the first IMP administration (Day 1) up to Day 58 Analysis was performed on the safety population. As is pre-specified in the study protocol, all adverse events were collected at the participant level.
Infections and infestations Upper respiratory tract infection	0.00% 0/39 • TEAE data was collected from the first IMP administration (Day 1) up to Day 58 Analysis was performed on the safety population. As is pre-specified in the study protocol, all adverse events were collected at the participant level.	2.6% 1/38 • Number of events 1 • TEAE data was collected from the first IMP administration (Day 1) up to Day 58 Analysis was performed on the safety population. As is pre-specified in the study protocol, all adverse events were collected at the participant level.
Immune system disorders Food allergy	0.00% 0/39 • TEAE data was collected from the first IMP administration (Day 1) up to Day 58 Analysis was performed on the safety population. As is pre-specified in the study protocol, all adverse events were collected at the participant level.	2.6% 1/38 • Number of events 1 • TEAE data was collected from the first IMP administration (Day 1) up to Day 58 Analysis was performed on the safety population. As is pre-specified in the study protocol, all adverse events were collected at the participant level.
Nervous system disorders Headache	2.6% 1/39 • Number of events 1 • TEAE data was collected from the first IMP administration (Day 1) up to Day 58 Analysis was performed on the safety population. As is pre-specified in the study protocol, all adverse events were collected at the participant level.	7.9% 3/38 • Number of events 3 • TEAE data was collected from the first IMP administration (Day 1) up to Day 58 Analysis was performed on the safety population. As is pre-specified in the study protocol, all adverse events were collected at the participant level.
Nervous system disorders Burning sensation	2.6% 1/39 • Number of events 1 • TEAE data was collected from the first IMP administration (Day 1) up to Day 58 Analysis was performed on the safety population. As is pre-specified in the study protocol, all adverse events were collected at the participant level.	0.00% 0/38 • TEAE data was collected from the first IMP administration (Day 1) up to Day 58 Analysis was performed on the safety population. As is pre-specified in the study protocol, all adverse events were collected at the participant level.
Nervous system disorders Migraine	2.6% 1/39 • Number of events 1 • TEAE data was collected from the first IMP administration (Day 1) up to Day 58 Analysis was performed on the safety population. As is pre-specified in the study protocol, all adverse events were collected at the participant level.	0.00% 0/38 • TEAE data was collected from the first IMP administration (Day 1) up to Day 58 Analysis was performed on the safety population. As is pre-specified in the study protocol, all adverse events were collected at the participant level.
Respiratory, thoracic and mediastinal disorders Cough	2.6% 1/39 • Number of events 1 • TEAE data was collected from the first IMP administration (Day 1) up to Day 58 Analysis was performed on the safety population. As is pre-specified in the study protocol, all adverse events were collected at the participant level.	0.00% 0/38 • TEAE data was collected from the first IMP administration (Day 1) up to Day 58 Analysis was performed on the safety population. As is pre-specified in the study protocol, all adverse events were collected at the participant level.
Skin and subcutaneous tissue disorders Dermatitis	0.00% 0/39 • TEAE data was collected from the first IMP administration (Day 1) up to Day 58 Analysis was performed on the safety population. As is pre-specified in the study protocol, all adverse events were collected at the participant level.	2.6% 1/38 • Number of events 1 • TEAE data was collected from the first IMP administration (Day 1) up to Day 58 Analysis was performed on the safety population. As is pre-specified in the study protocol, all adverse events were collected at the participant level.
Skin and subcutaneous tissue disorders Dermatitis atopic	0.00% 0/39 • TEAE data was collected from the first IMP administration (Day 1) up to Day 58 Analysis was performed on the safety population. As is pre-specified in the study protocol, all adverse events were collected at the participant level.	2.6% 1/38 • Number of events 1 • TEAE data was collected from the first IMP administration (Day 1) up to Day 58 Analysis was performed on the safety population. As is pre-specified in the study protocol, all adverse events were collected at the participant level.
Skin and subcutaneous tissue disorders Dermatitis contact	0.00% 0/39 • TEAE data was collected from the first IMP administration (Day 1) up to Day 58 Analysis was performed on the safety population. As is pre-specified in the study protocol, all adverse events were collected at the participant level.	2.6% 1/38 • Number of events 1 • TEAE data was collected from the first IMP administration (Day 1) up to Day 58 Analysis was performed on the safety population. As is pre-specified in the study protocol, all adverse events were collected at the participant level.
Skin and subcutaneous tissue disorders Pruritus	2.6% 1/39 • Number of events 1 • TEAE data was collected from the first IMP administration (Day 1) up to Day 58 Analysis was performed on the safety population. As is pre-specified in the study protocol, all adverse events were collected at the participant level.	0.00% 0/38 • TEAE data was collected from the first IMP administration (Day 1) up to Day 58 Analysis was performed on the safety population. As is pre-specified in the study protocol, all adverse events were collected at the participant level.
Skin and subcutaneous tissue disorders Skin hyperpigmentation	2.6% 1/39 • Number of events 2 • TEAE data was collected from the first IMP administration (Day 1) up to Day 58 Analysis was performed on the safety population. As is pre-specified in the study protocol, all adverse events were collected at the participant level.	0.00% 0/38 • TEAE data was collected from the first IMP administration (Day 1) up to Day 58 Analysis was performed on the safety population. As is pre-specified in the study protocol, all adverse events were collected at the participant level.
General disorders Vessel puncture site pain	0.00% 0/39 • TEAE data was collected from the first IMP administration (Day 1) up to Day 58 Analysis was performed on the safety population. As is pre-specified in the study protocol, all adverse events were collected at the participant level.	2.6% 1/38 • Number of events 1 • TEAE data was collected from the first IMP administration (Day 1) up to Day 58 Analysis was performed on the safety population. As is pre-specified in the study protocol, all adverse events were collected at the participant level.
General disorders Application site urticaria	2.6% 1/39 • Number of events 1 • TEAE data was collected from the first IMP administration (Day 1) up to Day 58 Analysis was performed on the safety population. As is pre-specified in the study protocol, all adverse events were collected at the participant level.	0.00% 0/38 • TEAE data was collected from the first IMP administration (Day 1) up to Day 58 Analysis was performed on the safety population. As is pre-specified in the study protocol, all adverse events were collected at the participant level.
General disorders Fatigue	2.6% 1/39 • Number of events 1 • TEAE data was collected from the first IMP administration (Day 1) up to Day 58 Analysis was performed on the safety population. As is pre-specified in the study protocol, all adverse events were collected at the participant level.	0.00% 0/38 • TEAE data was collected from the first IMP administration (Day 1) up to Day 58 Analysis was performed on the safety population. As is pre-specified in the study protocol, all adverse events were collected at the participant level.
General disorders Pain	2.6% 1/39 • Number of events 1 • TEAE data was collected from the first IMP administration (Day 1) up to Day 58 Analysis was performed on the safety population. As is pre-specified in the study protocol, all adverse events were collected at the participant level.	0.00% 0/38 • TEAE data was collected from the first IMP administration (Day 1) up to Day 58 Analysis was performed on the safety population. As is pre-specified in the study protocol, all adverse events were collected at the participant level.
Investigations Activated partial thromboplastin time prolonged	0.00% 0/39 • TEAE data was collected from the first IMP administration (Day 1) up to Day 58 Analysis was performed on the safety population. As is pre-specified in the study protocol, all adverse events were collected at the participant level.	2.6% 1/38 • Number of events 1 • TEAE data was collected from the first IMP administration (Day 1) up to Day 58 Analysis was performed on the safety population. As is pre-specified in the study protocol, all adverse events were collected at the participant level.
Investigations Blood creatine phosphokinase increased	2.6% 1/39 • Number of events 1 • TEAE data was collected from the first IMP administration (Day 1) up to Day 58 Analysis was performed on the safety population. As is pre-specified in the study protocol, all adverse events were collected at the participant level.	0.00% 0/38 • TEAE data was collected from the first IMP administration (Day 1) up to Day 58 Analysis was performed on the safety population. As is pre-specified in the study protocol, all adverse events were collected at the participant level.
Injury, poisoning and procedural complications Limb injury	0.00% 0/39 • TEAE data was collected from the first IMP administration (Day 1) up to Day 58 Analysis was performed on the safety population. As is pre-specified in the study protocol, all adverse events were collected at the participant level.	2.6% 1/38 • Number of events 1 • TEAE data was collected from the first IMP administration (Day 1) up to Day 58 Analysis was performed on the safety population. As is pre-specified in the study protocol, all adverse events were collected at the participant level.
Injury, poisoning and procedural complications Skin abrasion	2.6% 1/39 • Number of events 1 • TEAE data was collected from the first IMP administration (Day 1) up to Day 58 Analysis was performed on the safety population. As is pre-specified in the study protocol, all adverse events were collected at the participant level.	0.00% 0/38 • TEAE data was collected from the first IMP administration (Day 1) up to Day 58 Analysis was performed on the safety population. As is pre-specified in the study protocol, all adverse events were collected at the participant level.
Injury, poisoning and procedural complications Traumatic haemorrhage	2.6% 1/39 • Number of events 1 • TEAE data was collected from the first IMP administration (Day 1) up to Day 58 Analysis was performed on the safety population. As is pre-specified in the study protocol, all adverse events were collected at the participant level.	0.00% 0/38 • TEAE data was collected from the first IMP administration (Day 1) up to Day 58 Analysis was performed on the safety population. As is pre-specified in the study protocol, all adverse events were collected at the participant level.

Additional Information

Trial Transparency Team

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Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place

Restriction type: OTHER