Safety and Efficacy of CD5024 0.3% Cream in Subjects With Atopic Dermatitis

Study Overview
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Brief Summary
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Exploratory, multi-centric, randomized, vehicle-controlled, investigator-blind, parallel group study, involved participants with chronic lesions of Atopic Dermatitis (AD) to evaluate the local and systemic safety of CD5024 0.3% cream over a 6-week treatment period compared to its vehicle.

Detailed Description
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Study application was performed once daily, 7 days a week for 6 weeks.

Official Title
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Safety and Efficacy of CD5024 0.3% Cream in Subjects With Atopic Dermatitis

Conditions
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Atopic Dermatitis

Intervention / Treatment
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* Drug: CD5024 0.3% cream
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: The participant was a male or female aged 18 to 60 years old inclusive at Screening. The participant presented with a total body surface area (tBSA) less than or equal to (>=) 2 square meter (m^2) at Screening. The participant had atopic dermatitis for at least 6 months prior to Day 1. The clinical diagnosis of atopic dermatitis must be confirmed with the criteria of Hanifin and Rajka at the screening visit. Atopic dermatitis must be stable for at least one month before the screening visit (according to participant). The participant had a Body Surface Area (BSA) affected by AD ranging from 1% inclusive to 10% inclusive at Day 1, excluding scalp and genitals. The participant had an overall Investigator's Global Assessment (IGA) score of 3 (moderate) at Day 1; Exclusion Criteria: The participant was a pregnant female, is breastfeeding or intends to conceive a child during the study, The participant had any uncontrolled or serious disease, or any medical or surgical condition, that may either interfere with the interpretation of the clinical trial results (e.g. extensive scaring or pigmented lesion in a treated area), and/or put the participant at significant risk according to Investigator's judgment if he/she participates in the clinical trial (e.g. active cancer, AIDS, insulin-dependent diabetes…) at Screening or Day 1. The participant presented with an acute flare of AD at Day 1. The participant had active cutaneous bacterial or viral infection in any treated area at baseline (e.g. clinically infected AD) at Screening or Day 1. The participant had a history of confounding skin condition (e.g. psoriasis, erythroderma) or a history of Netherton syndrome at Screening. The participant had a past history of serious persistent neurological disorders such as seizures, multiple sclerosis, or neurological signs or symptoms at Screening.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CD5024 0.3% cream<br> | Drug: CD5024 0.3% cream<br>* Participants applied CD5024 0.3% cream topically in the evening to the affected areas as a thin film corresponding to approximately 2 milligrams per centimeter square (mg/cm^2) once daily for 6 weeks.<br>* Other names: Ivermectin;|
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* Participants applied placebo matched to CD5024 0.3% cream topically in the evening to the affected areas as a thin film corresponding to approximately 2 mg/cm^2 once daily for 6 weeks.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Eczema Area and Severity Index (EASI) Score at Day 43 | The EASI score was used to measure the severity and extent of atopic dermatitis (AD) and measures erythema, induration, excoriation and lichenification on 4 anatomic regions of the body: head, trunk, upper and lower extremities. The total EASI score ranges from 0 (minimum) to 72 (maximum), with the higher scores indicated the worse severity of AD. All missing values were imputed by Last Observation Carried Forward (LOCF). | Baseline, Day 43 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent Change From Baseline in EASI at Each Visit | The EASI score was used to measure the severity and extent of atopic dermatitis (AD) and measures erythema, induration, excoriation and lichenification on 4 anatomic regions of the body: head, trunk, upper and lower extremities. The total EASI score ranges from 0 (minimum) to 72 (maximum) points, with the higher scores indicated the worse severity of AD. All missing values were imputed by LOCF. | Baseline, Days 8,15, 22, 29, 36 and 43 | 
| Percentage of Participants Who Achieved an Investigator Global Assessment (IGA) Score of 1 (Almost Clear) or 0 (Clear) | IGA scale consisted of 5 grades (0-4) among which 0 = Clear (Minor, residual discoloration, no erythema or induration/papulation, no oozing/crusting), 1 = Almost clear (Trace, faint pink erythema with almost no induration/papulation and no oozing/crusting), 2 = Mild (Faint pink erythema with mild induration/papulation and no oozing/crusting), 3 = Moderate (Pink-red erythema with moderate induration/papulation and there may be some oozing/crusting.), 4 = Severe (Deep/bright red erythema with severe induration/papulation with oozing/crusting). Success rate was defined as percentage of participants who achieved an IGA score of 1 (almost clear) or 0 (Clear) at specified visits. All missing values were imputed by LOCF. | Days 8, 15, 22, 29, 36 and 43 | 
| Percent Change From Baseline in Total Sum Score (TSS) at Each Visit | The TSS was the sum of individual clinical severity scores for 5 signs of AD (erythema, induration/papulation, oozing/crusting, excoriation and lichenification). The severity of each sign was evaluated by using a 4-graded scale (0: none; 1: mild; 2: moderate; 3: severe). The total score ranges from 0 to 15, where higher score indicated worse severity of AD. All missing values were imputed by LOCF. | Baseline, Days 8, 15, 22, 29, 36 and 43 | 
| Percent Change From Baseline in Modified Objective Scoring Atopic Dermatitis (SCORAD) at Each Visit | SCORAD index uses the rule of nines to assess disease extent and evaluates 6 clinical characteristics to determine disease severity: (1) erythema, (2) edema/papulation, (3) oozing/crusts, (4) excoriation, (5) lichenification, and (6) dryness on a scale of 0 to 3 (0=absence, 1=mild, 2=moderate, 3=severe). The SCORAD index also assesses subjective symptoms of pruritus and sleep loss with visual analog scale (VAS) where 0 is no itching or no trouble sleeping and 10 is unbearable itching or a lot of trouble sleeping. These 3 aspects: extent of disease (A: 0-1-2), disease severity (B: 0-18), & subjective symptoms (C: 0-20) combine using A/5 + 7*B/2+ C to give a maximum possible score of 103, where 0 = no disease and 103 = severe disease. Higher scores indicated worse outcome. All missing values were imputed by LOCF. | Baseline, Days 8, 15, 22, 29, 36 and 43 | 
| Change From Baseline in Pruritus Numerical Rating Scale (NRS) at Each Visit | Pruritus NRS was a scale that was used by the participants to report the intensity of their pruritus (itch) during the last 24 hours. For maximum itch intensity: the scores were provided on a scale of 0 to 10, with 0 = 'no itch' and 10 = 'worst itch imaginable', where higher score indicated very severe itch. All missing values were imputed by LOCF. | Baseline, Weeks 1, 2, 3, 4, 5 and 6 | 
| Change From Baseline in Pruritus Verbal Rating Scale (VRS) Score at Day 43 | Participants were asked for a response that best described their pruritus intensity in last 24 hours, to rate their itch using a list of adjectives describing different levels of symptom intensity rated on a scale of 0 to 3 that is (i.e.) 0 = No itch, 1 = low, 2 = Moderate and 3 = Severe, where higher score indicated very severe itch. All missing values were imputed by LOCF. | Baseline, Day 43 |