Phase 2a Study to Evaluate the Efficacy and Safety of MEDI9929 in Adults With Atopic Dermatitis

Study Overview
=================
Brief Summary
-----------------
To assess the efficacy and safety of MEDI9929 in adult subjects with Atopic Dermatitis

Detailed Description
-----------------
This is a Phase 2a, randomized, double-blinded, placebo-controlled study to evaluate the efficacy and safety of MEDI9929 administered subcutaneously to adult subjects with moderate to severe Atopic Dermatitis. Subjects will be randomized in a 1:1 fashion and will be stratified at screening. Approximately 100 subjects are planned to be randomized at approximately 35 sites in 6 countries

Official Title
-----------------
A Phase 2a, Randomized, Double-blinded, Placebo-controlled Study to Evaluate the Efficacy and Safety of MEDI9929 in Adult Subjects With Moderate-to-Severe Atopic Dermatitis

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

Intervention / Treatment
-----------------
* Biological: MEDI9929
* Biological: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: AD meeting Hanifin and Rajka criteria Age 18-75 years inclusive at screening Atopic dermatitis that affects greater than/equal to 10% body surface area Moderate to severe AD Effective birth control in line with protocol details Exclusion Criteria: Active dermatologic conditions which may confuse the diagnosis of Atopic Dermatitis Hepatitis B, C or HIV Pregnant or breastfeeding History of anaphylaxis following any biologic therapy History of clinically significant infections within 4 weeks prior to Visit 3 Diagnosis of helminth parasitic infection within 6 months to screening History of Cancer except basal cell Receipt of any marketed or investigational biologic agent within 4 months to visit 3 Any clinically relevant abnormal finding Major surgery within 8 weeks prior to Visit 1

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 75 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: MEDI9929 280 mg<br>Participants will receive 6 subcutaneous doses of MEDI9929 280 mg every 2 weeks for 12 weeks, with the last dose at Week 10. | Biological: MEDI9929<br>* Participants will receive 6 subcutaneous doses of MEDI9929 280 mg every 2 weeks for 12 weeks, with the last dose at Week 10.<br>|
| Placebo Comparator: Placebo<br>Participants will receive 6 subcutaneous doses of placebo every 2 weeks for 12 weeks, with the last dose at Week 10. | Biological: Placebo<br>* Participants will receive 6 subcutaneous doses of placebo every 2 weeks for 12 weeks, with the last dose at Week 10.<br>|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Achieving Greater Than or Equal to (>=) 50 Percent (%) Reduction From Baseline in Eczema Area and Severity Index (EASI 50) at Week 12 | The eczema area and severity index (EASI) evaluates 4 natural anatomical regions for severity (0 [none] to 3 [severe]) and extent of key disease signs and focuses on the key acute and chronic signs of inflammation (erythema, induration/papulation, excoriation, and lichenification). The total score is the sum of the four body-region scores, maximum=72, minimum=0. The higher values indicating more severe disease. The EASI50 responder defined as a participant who achieved at least 50% reduction in EASI score from baseline. | Baseline (Day 1) and Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Achieving >= 75 % Reduction From Baseline in EASI75 at Week 12 | The EASI evaluates 4 natural anatomical regions for severity (0 [none] to 3 [severe]) and extent of key disease signs and focuses on the key acute and chronic signs of inflammation (erythema, induration/papulation, excoriation, and lichenification). The total score is the sum of the four body-region scores, maximum=72, minimum=0. The higher values indicating more severe disease. The EASI75 responder defined as a participant who achieves at least a 75% reduction in EASI score from baseline. | Baseline (Day 1) and Week 12 | 
| Mean Change From Baseline in EASI Total Score at Week 12 | The EASI evaluates 4 natural anatomical regions for severity (0 [none] to 3 [severe]) and extent of key disease signs and focuses on the key acute and chronic signs of inflammation (erythema, induration/papulation, excoriation, and lichenification). The total score is the sum of the four body-region scores, maximum=72, minimum=0. The higher values indicating more severe disease. | Baseline (Day 1) and Week 12 | 
| Percentage of Participants Achieving Investigator's Global Assessment (IGA) Response of 0 (Clear) or 1 (Almost Clear) and at Least a 2-Grade Reduction From Baseline | The investigator's global assessment (IGA) allows investigators to assess overall disease severity at one given time point and consists of a 5-point severity scale from clear to severe disease (0 = clear, 1 = almost clear, 2 = mild disease, 3 = moderate disease, and 4 = severe disease). A participant has IGA response if they achieve a score of 0 (clear) or 1 (almost clear) and at least a 2-grade reduction from baseline. | Baseline (Day 1) and Week 12 | 
| Mean Change From Baseline in the Scoring of Atopic Dermatitis (SCORAD) at Week 12 | The scoring of atopic dermatitis (SCORAD) is a clinical tool for assessing the severity (that is, extent, intensity) of atopic dermatitis (AD). The tool evaluates the extent and intensity of the AD lesions, along with participant symptoms. The range of the SCORAD is 0-103, where 0 indicates no eczema. The higher values indicating more severe disease. | Baseline (Day 1) and Week 12 | 
| Percentage of Participants Achieving >= 50% Reduction From Baseline in SCORAD 50 | The SCORAD is a clinical tool for assessing the severity (that is, extent, intensity) of atopic dermatitis (AD). The tool evaluates the extent and intensity of the AD lesions, along with participant symptoms. The range of the SCORAD is 0-103, where 0 indicates no eczema. The higher values indicating more severe disease. The SCORAD 50 responder defined as a participant who achieves at least a 50% reduction in SCORAD score from baseline. | Baseline (Day 1) and Week 12 | 
| Percentage of Participants Achieving >= 75% Reduction From Baseline in SCORAD 75 | The SCORAD is a clinical tool for assessing the severity (that is, extent, intensity) of atopic dermatitis (AD). The tool evaluates the extent and intensity of the AD lesions, along with participant symptoms. The range of the SCORAD is 0-103, where 0 indicates no eczema. The higher values indicating more severe disease. The SCORAD 75 responder is defined as a participant who achieves at least a 75% reduction in SCORAD score from baseline. | Baseline (Day 1) and Week 12 | 
| Mean Change From Baseline in Average Pruritus Numeric Rating Scale (NRS) at Week 12 | Pruritus is assessed using an Numeric Rating Scale (NRS) (0 - 10) with 0= no itch and 10= worst imaginable itch. Daily pruritus assessments were summarized as weekly peak score and a change from baseline in weekly peak score was calculated. | Baseline (Day 1) and Week 12 | 
| Mean Change From Baseline in 5-D Pruritus Score at Week 12 | The 5-D pruritus scale is a brief questionnaire designed to assess itch. This scale takes into account the multidimensional nature of pruritus, its impact on quality of life, and is capable of detecting change over time. The 5-D pruritus scale included 5 domains (duration, degree, direction, disability, and distribution of pruritus). The total 5-D score was obtained by scoring each of the domains separately and then summing them together. 5-D total scores ranged between 5 (no pruritus) and 25 (most severe pruritus). The higher values indicating more severe pruritus. | Baseline (Day 1) and Week 12 | 
| Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) | An Adverse event is any unfavourable and unintended signs (including abnormal laboratory findings), symptoms, or diseases temporally associated with use of investigational product, whether or not considered related to investigational product. Serious adverse event is any AE that resulted in:death;inpatient hospitalization or prolongation of existing hospitalization;persistent or significant disability or incapacity;is life-threatening;is a congenital anomaly/birth defect in offspring of a study participant;or was an important medical event that may not have resulted in death, threatened life,or required hospitalization and that, based on appropriate medical judgment, may have jeopardized participant and may have required medical or surgical intervention to prevent one of outcomes above. TEAEs are defined as AEs present at baseline that worsened in intensity after administration of study drug, or events absent at baseline that emerged after administration of study drug until Week 22. | From treatment administration (Day1) to 22 weeks | 
| Mean Trough Serum Concentration of MEDI9929 | The mean serum concentrations of MEDI9929 was observed at specified timepoints. | Week 0 (Pre dose), Weeks 4, 8, and 12 (post dose) | 
| Number of Participants Who Developed Detectable MEDI9929 Anti-drug Antibodies | A participant was considered ADA-positive across the study if they had a positive reading (titer of 50 or higher) at any time point during the study period. | Baseline (Day 1) to Week 22 | 

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