An Ascending Multiple Dose Study of VTP-38543 in Adult Participants With Mild to Moderate Atopic Dermatitis

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics and preliminary clinical efficacy of VTP-38543 administered as a cream, twice-daily, for 28 days in otherwise healthy adult male and female participants with mild to moderate atopic dermatitis.

Detailed Description
-----------------
This is a randomized, double-blind, vehicle-controlled study to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics and preliminary clinical efficacy of VTP-38543 following twice-daily, every twelve hours (Q12h) administration for 28 days in otherwise healthy adult male and female participants with mild to moderate atopic dermatitis. Evaluation of three ascending doses in three dose panels is planned for this trial. Dose Panel 1 (VTP-38543 0.05%) and Panel 2 (VTP-38543 0.15%) will each enroll 30 participants and randomize 20 to VTP-38543 and 10 to matching vehicle control (Vehicle without Transcutol®P). Dose Panel 3 (VTP-38543 1%) will enroll 40 participants and randomize 20 to VTP-38543 and 20 to matching vehicle control (Vehicle with Transcutol®P). A total of approximately 100 participants will participate in the trial.

Official Title
-----------------
A Randomized, Double-Blind, Vehicle-Controlled Ascending Multiple Dose and Clinical Proof-Of-Concept Study to Assess the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of VTP-38543 in Adult Patients With Mild to Moderate Atopic Dermatitis

Conditions
-----------------
Dermatitis, Atopic

Intervention / Treatment
-----------------
* Drug: VTP-38543
* Other: Vehicle with Transcutol®P
* Other: Vehicle without Transcutol®P


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Mild to moderate atopic dermatitis with a minimum of 3 to a maximum of 15% body surface area (BSA) involvement Investigator Global Assessments (IGA) score of 2 or 3 Body Mass Index (BMI) = 18 - 35 kg/m^2 Negative Pregnancy test for females Exclusion Criteria: Treatment for atopic dermatitis with systemic medications, topical agents, and parenteral biological/monoclonal antibody agents, within specific time period prior to dosing. Organ dysfunction or any clinically significant deviation from normal in vital signs, physical examinations, labs, and Electrocardiogram (ECG) findings Major surgery within 3 months of Screening Use of prescription drugs, sedative antihistamine, medical devices for treatment of atopic dermatitis (AD), and topical products containing urea and/or ceramides within 14 prior to dosing Excessive sun exposures, use of tanning booths or other ultraviolet (UV) light sources 4 weeks prior to dosing

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: VTP-38543 0.05%<br>VTP-38543 0.05% administered topically every 12 hours for 28 days. | Drug: VTP-38543<br>* VTP-38543 topical cream<br>|
| Experimental: VTP-38543 0.15%<br>VTP-38543 0.15% administered topically every 12 hours for 28 days. | Drug: VTP-38543<br>* VTP-38543 topical cream<br>|
| Placebo Comparator: Vehicle without Transcutol®P<br>Vehicle without Transcutol®P administered topically every 12 hours for 28 days. | Other: Vehicle without Transcutol®P<br>* Vehicle matching VTP-38543 cream without Transcutol®P<br>* Other names: Transcutol®P is Diethylene Glycol Monoethyl Ether, NF.;|
| Experimental: VTP-38543 1%<br>VTP-38543 1% administered topically every 12 hours for 28 days. | Drug: VTP-38543<br>* VTP-38543 topical cream<br>|
| Placebo Comparator: Vehicle with Transcutol®P<br>Vehicle with Transcutol®P administered topically every 12 hours for 28 days. | Other: Vehicle with Transcutol®P<br>* Vehicle matching VTP-38543 cream with Transcutol®P<br>* Other names: Transcutol®P is Diethylene Glycol Monoethyl Ether, NF.;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Treatment-related Adverse Events (AEs) | An Adverse Event is any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. The number of participants with AEs related to treatment are reported. | Baseline (Day 0) to Day 35 | 
| Number of Participants With Clinically Significant Changes in Clinical Laboratory Values | Clinical Laboratory tests included chemistry, hematology and urinalysis tests collected during the study. The investigator determined if the changes in laboratory results were clinically significant. | Baseline (Day 0) to Day 35 | 
| Number of Participants With Clinically Significant Changes in Vital Signs | Vital signs included blood pressure, pulse, respiration rate and body temperature. The investigator determined if the changes in vital sign results were clinically significant. | Baseline (Day 0) to Day 35 | 
| Number of Participants With Clinically Significant Changes in Electrocardiogram (ECG) Values | A standard 12-lead ECG was performed. The investigator determined if the changes in ECG results were clinically significant. | Baseline (Day 0) to Day 35 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Plasma Concentration (Cmax) for VTP-38543-001 |  | Day 0 (pre-dose, 1, 2, 4, 6, 9, and 12 hours post first dose), and Day 27 (pre-dose, 1, 2, 4, 6, 9, 12, 24, 48, and 72 hours post last dose) | 
| Time to Maximum Plasma Concentrations (Tmax) for VTP-38543 |  | Day 0 (pre-dose, 1, 2, 4, 6, 9, and 12 hours post first dose), and Day 27 (pre-dose, 1, 2, 4, 6, 9, 12, 24, 48, and 72 hours post last dose) | 
| Area Under the Plasma Concentration Versus Time Curve, From Time 0 to the Last Measurable Concentration (AUClast) for VTP-38543 |  | Day 0 (pre-dose, 1, 2, 4, 6, 9, and 12 hours post first dose), and Day 27 (pre-dose, 1, 2, 4, 6, 9, 12, 24, 48, and 72 hours post last dose) | 
| Area Under the Plasma Concentration Versus Time Curve, From Time 0 to 12 Hours (AUC0-12hr) for VTP-38543 |  | Day 0 (pre-dose, 1, 2, 4, 6, 9, and 12 hours post first dose), and Day 27 (pre-dose, 1, 2, 4, 6, 9, 12, 24, 48, and 72 hours post last dose) | 
| Elimination Half-life (t½) for VTP-38543 |  | Day 0 (pre-dose, 1, 2, 4, 6, 9, and 12 hours post first dose), and Day 27 (pre-dose, 1, 2, 4, 6, 9, 12, 24, 48, and 72 hours post last dose) | 
| Percentage Change From Baseline in Total Body Surface Area (BSA) | Percent BSA was estimated using the palmar surface of the participant's hand up to the proximal interphalangeal joint, including the thumb, to approximate 1% of the participant's BSA. The overall BSA affected by atopic dermatitis was evaluated from 0 to 100% and divided by 5 for a maximum of 20. A negative percentage change indicates improvement. | Baseline (Day 0) to Day 28 | 
| Percentage Change From Baseline in Investigator Global Assessments (IGA) Score | The investigator assessed the participant's atopic dermatitis using the 5-point IGA where 0=clear (Minor, residual discoloration, no erythema or induration/papulation, no oozing/crusting) to 4=Severe disease (Deep/bright red erythema with severe induration/papulation with oozing/crusting). A negative percentage change indicates improvement. | Baseline (Day 0) to Day 28 | 
| Percentage Change From Baseline in Scoring Atopic Dermatitis (SCORAD) Score | The investigator assessed severity of atopic dermatitis (AD) using scoring atopic dermatitis (SCORAD) score obtained from different individual scales. 6-items: erythema, edema/papulation, oozing/crusts, excoriation, lichenification, and dryness were graded on a 4-point scale where 0=Absent to 3=Severe. The individual scores were added together to get a score of 0 to 18 that was multiplied by 3.5 for a score of 0 to 63. The overall BSA affected by AD (0 to 100 %) was divided by 5 for a score 0 to 20. The participant used a 10-point Visual Analog Scale (VAS) to evaluate loss of sleep and the occurrence of pruritus averaged over the last 3 days where 0=None to Worst Imaginable. The sum of the 2 VAS scores was 0 to 20. The above measures were added together for a total possible SCORAD score of 0 (best) to 103 (worst). A negative percentage change indicates improvement. | Baseline (Day 0) to Day 28 | 
| Percentage Change From Baseline Eczema Area and Severity Index (EASI) | The investigator assessed four body regions: Head and neck, Upper extremities, Trunk including axillae and groin, and Lower extremities including buttocks. Each body region was scored based on BSA where 0=No involvement to 6=90-100%. Each body region was assessed for erythema, infiltration/papulation, excoriation and lichenification using a 4-point scale where 0=None to 3=Severe. EASI total score was determined by combining the individual scores for each of the 4 body regions. The total for each region was calculated by [erythema + infiltration+ excoriation + lichenification * area involvement * a constant (constants Head and Neck=0.1, Upper Limbs=0.2, Trunk=0.3, Lower Limbs=0.4)]. The EASI total score was determined by combining the individual scores for each of the 4 body regions for a total possible score of 0 (best) to 72 (worst). A negative percentage change indicates improvement. | Baseline (Day 0) to Day 28 | 
| Percentage Change From Baseline in Pruritus VAS Score | The participant used a 10-point VAS to assess the occurrence of pruritus (itchy skin) over the last 3 days where 0= None to 10=Worst Imaginable for a total possible score of 0 to 10. A negative percentage change indicates improvement. | Baseline (Day 0) to Day 28 | 
| Percentage Change From Baseline in VAS Sleep Score | The participant used a 10-point VAS to evaluate loss of sleep averaged over the last 3 days where 0= None to 10=Worst imaginable for a total possible score of 0 to 10. A negative percentage change indicates improvement. | Baseline (Day 0) to Day 28 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Eczema