Clinical trial NCT04992546: Phase 2a Study of the Safety, Tolerability, and Pharmacokinetics of Topically Administered PRN473 (SAR444727) in Patients With Mild to Moderate Atopic Dermatitis
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Atopic Dermatitis
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
First posted: 2021-08-05
Enrollment: 39
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs)
timeFrame: From the first IMP administration (Day 1) up to Day 58
measure: Number of Participants With Potentially Clinically Significant Abnormalities (PCSA): Vital Signs
timeFrame: From the first IMP administration (Day 1) up to Day 45
measure: Number of Participants With PCSA in 12-Lead Electrocardiogram (ECG)
timeFrame: From the first IMP administration (Day 1) up to Day 45
measure: Number of Participants With PCSA: Hematology
timeFrame: From the first IMP administration (Day 1) up to Day 45
measure: Number of Participants With PCSA: Electrolyte Parameters
timeFrame: From the first IMP administration (Day 1) up to Day 45
measure: Number of Participants With PCSA: Metabolic Parameters
timeFrame: From the first IMP administration (Day 1) up to Day 45
measure: Number of Participants With PCSA: Renal Function Parameters
timeFrame: From the first IMP administration (Day 1) up to Day 45
measure: Number of Participants With PCSA: Liver Function Parameters
timeFrame: From the first IMP administration (Day 1) up to Day 45
measure: Number of Participants With PCSA: Urinalysis
timeFrame: From the first IMP administration (Day 1) up to Day 45
measure: Percentage of Participants With Application-Site Event During Double-Blind Period
timeFrame: From the first IMP administration (Day 1) up to Week 2
Secondary outcomes:
measure: Maximum Plasma Concentration (Cmax) of SAR444727
timeFrame: Day 1, 4 hours post-dose; Day 15, 1 hour post-dose and Day 43, 12 hours post-dose
Other outcomes:
Locations:
city: Long Beach
country: United States
facility: Collaborative Neuroscience Research-Site Number:8400004
state: California
city: Los Angeles
country: United States
facility: California Allergy & Asthma Medical Group-Site Number:8400008
state: California
city: Miami
country: United States
facility: Florida International Research Center-Site Number:8400017
state: Florida
city: Sweetwater
country: United States
facility: Lenus Research & Medical Group-Site Number:8400006
state: Florida
city: Tampa
country: United States
facility: Clinical Research Trials of Florida, Inc-Site Number:8400013
state: Florida
city: Columbus
country: United States
facility: Remington Davis Inc-Site Number:8400012
state: Ohio
city: Bryan
country: United States
facility: J&S Studies-Site Number:8400015
state: Texas
city: Houston
country: United States
facility: Center for Clinical Studies, LTD. LLP-Site Number:8400014
state: Texas
city: San Antonio
country: United States
facility: Progressive Clinical Research-Site Number:8400002
state: Texas
city: Hamilton
country: Canada
facility: Investigational Site Number :1240008
state: Ontario
city: London
country: Canada
facility: Investigational Site Number :1240007
state: Ontario
city: Quebec
country: Canada
facility: Investigational Site Number :1240002
Study officials:
References: