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

Principia Biopharma

Status and phase: Completed; Phase 2

Conditions: Atopic Dermatitis

Treatments: Drug: Placebo; Drug: PRN473 (SAR444727)

Study type: Interventional

Funder types: Industry

Identifiers

NCT04992546

PRN473-0005 (Other Identifier)

U1111-1260-4204 (Registry Identifier)

ACT17131

Details and patient eligibility

About

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.

Full description

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

Enrollment: 39 patients

Sex: All

Ages: 18 to 70 years old

Volunteers: No 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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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39 participants in 2 patient groups, including a placebo group

SAR444727 5% BID per lesion

Experimental group

Description:

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). 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.

Treatment:

Drug: PRN473 (SAR444727)

Placebo then SAR444727 5% BID per lesion

Placebo Comparator group

Description:

Multiple topical doses of placebo for 14 days, and PRN473 (SAR444727) for 28 days

Treatment:

Drug: PRN473 (SAR444727)

Drug: Placebo