Efficacy and Safety of MEDI3506 in Adult Subjects With Atopic Dermatitis

Study Overview
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Brief Summary
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This is a research study to determine the efficacy and safety of investigational drug MEDI3506 for the treatment of adult subjects with Atopic Dermatitis.

Detailed Description
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This is a research study to determine the efficacy and safety of investigational drug MEDI3506 for the treatment of adult subjects with Atopic Dermatitis. Each participant will be assigned randomly to a treatment arm, which could be different strengths of the active treatment or a placebo which does not contain active treatment. Both Participants and investigators will be masked to the treatment assignment. Approximately 152 participants will take part in this study. There is a 4 weeks screening period to determine eligibility. After eligibility is confirmed, participants will receive investigational drug or placebo during the 16 weeks treatment period. This is then followed by an 8-week follow-up period.

Official Title
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A Phase 2 Randomized, Double-blinded, Placebo-controlled Study to Evaluate the Efficacy and Safety of MEDI3506 in Adult Subjects With Moderate-to-severe Atopic Dermatitis

Conditions
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Atopic Dermatitis

Intervention / Treatment
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* Drug: MEDI3506
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18 to 65 years inclusive at the time of consent. Body mass index between 19.0 and 40.0 kg/m2 inclusive. Documented history of chronic AD, for at least 1 year prior to screening Visit 1. Meets at minimum 1 of the criteria, as follows: History of inadequate response to topical medications for AD Subject intolerance to treatment with topical medications for AD, or Topical medications are otherwise medically inadvisable AD that affects ≥ 10% of the body surface area (BSA). An EASI score of ≥ 12 at Visit 1 and ≥ 16 at Visit 3 (Day 1). An IGA score of ≥ 3. Exclusion Criteria: Any active medical or psychiatric condition, or other reason, that would interfere with evaluation of the investigational product or interpretation of subject safety or study results. Any other clinically relevant abnormal findings from physical examination (including vital signs and electrocardiogram [ECG]) or from safety laboratory analysis. Active dermatologic conditions that might confound the diagnosis of AD or would interfere with the assessment of the skin. Known active allergic or irritant contact dermatitis.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Participants will be randomised to receive MEDI3506 dose 1, MEDI3506 Dose 2 or MEDI3506 dose 3 or placebo.
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MEDI3506 at dose level 1<br>Participant will receive multiple doses of MEDI3506 at dose level 1. | Drug: MEDI3506<br>* multiple doses<br>|
| Experimental: MEDI3506 at dose level 2<br>Participant will receive multiple doses of MEDI3506 at dose level 2. | Drug: MEDI3506<br>* multiple doses<br>|
| Experimental: MEDI3506 at dose level 3<br>Participant will receive multiple doses of MEDI3506 at dose level 3. | Drug: MEDI3506<br>* multiple doses<br>|
| Placebo Comparator: Placebo<br>Participant will receive multiple doses of Placebo | Drug: Placebo<br>* multiple doses<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent Change From Baseline to Week 16 in EASI Score | The EASI evaluates 4 anatomic regions for severity and extent of key disease signs and focuses on the acute and chronic signs of inflammation (ie, erythema, edema, papulation, excoriation, and lichenification). The maximum score is 72, with higher values indicating more severe disease. Analysis was performed using mixed effect model for repeated measures and MCP-mod dose response model. | Week 16 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Subjects Achieving a 90% Reduction From Baseline in EASI Score at Week 16 | To further assess the effects of MEDI3506 compared with placebo on AD disease severity, in adult subjects with moderate-to-severe AD. Responders are subjects who achieved at least 90% reduction from baseline in EASI score. | Week 16 | 
| Percentage of Subjects Achieving a 75% Reduction From Baseline in EASI Score at Week 16 | To further assess the effects of MEDI3506 compared with placebo on AD disease severity, in adult subjects with moderate-to-severe AD. Responders are subjects who achieved at least 75% reduction from baseline in EASI score. | Week 16 | 
| Percentage of Subjects Achieving a 50% Reduction From Baseline in EASI Score at Week 16 | To further assess the effects of MEDI3506 compared with placebo on AD disease severity, in adult subjects with moderate-to-severe AD. Responders are subjects who achieved at least 50% reduction from baseline in EASI score. | Week 16 | 
| Percentage of Subjects Achieving an IGA of 0 (Clear) or 1 (Almost Clear) With at Least a 2 Grade Reduction From Baseline Score at Week 16 | The IGA allows investigators to assess overall AD disease severity at 1 given time point and consists of a 5-point severity scale from clear to very severe disease (0 = clear, 1 = almost clear, 2 = mild disease, 3 = moderate disease, and 4 = severe disease). | Week 16 | 
| Percentage of Subjects Achieving a Reduction of ≥ 3 From Baseline to Week 16 in Weekly Mean of Daily Peak Pruritus NRS | Peak pruritus (ie, worst itch experienced in the previous 24 hours) assessed using an Numerical Rating Scale (NRS; 0 to 10) with 0 = no itch and 10 = worst imaginable itch. The daily assessments were summarised as a weekly mean. | Week 16 | 
| Change From Baseline to Week 16 in Weekly Mean of Daily Peak Pruritus NRS | Peak pruritus (ie, worst itch experienced in the previous 24 hours) assessed using an Numerical Rating Scale (NRS; 0 to 10) with 0 = no itch and 10 = worst imaginable itch. The daily assessments were summarised as a weekly mean. | Week 16 | 
| Change From Baseline to Week 16 in Weekly Mean of Daily Peak Skin Pain NRS | Skin pain (ie, worst skin pain experienced in the previous 24 hours) assessed using an NRS (0 to 10) with 0 = no pain and 10 = worst imaginable pain. The daily assessments were summarised as a weekly mean. | Week 16 | 
| SCORAD: Percent Change From Baseline to Week 16 | SCORAD is a clinical tool for assessing the severity of AD that evaluates the extent and intensity of AD lesions, in addition to subjective symptoms. The maximum total score is 103, with higher values indicating more severe disease. | Week 16 | 
| Change From Baseline to Week 16 in Percentage Body Surface Area (BSA) Affected by AD | Change in percentage of body surface area (BSA) affected by AD from baseline at week 16. | Week 16 | 
| Change From Baseline to Week 16 in DLQI | The Dermatology Life Quality Index (DLQI) is a 10-item, patient- completed, health-related quality of life assessment of dermatology conditions with a recall period of 1 week. Each item is scored on a 4-point Likert scale with 0 = not at all ⁄not relevant, 1 = a little, 2 = a lot, and 3 = very much. The score from each item is summed, and the maximum total score is 30 while the minimum score is 0. Higher score means highest (adverse) effect on participant's life. | Week 16 | 
| Patient Description of Atopic Dermatitis or Eczema From Patient Global Impression of Severity at Week 16 | The Patient Global Impression of Severity (PGI-S) is a tool that allows patients to rate the severity of a condition over the past 7 days with response options of No symptoms, Very mild, Mild, Moderate, Severe and Very severe. | Week 16 | 
| Change From Baseline to Week 16 in POEM | The Patient-Oriented Eczema Measure (POEM) is a 7-item questionnaire for assessing disease symptoms including dryness, itching, flaking, cracking, sleep loss, bleeding, and weeping occurring in the past week. Each item is scored on a 5-point scale with 0 = no days, 1 = 1 to 2 days, 2 = 3 to 4 days, 3 = 5 to 6 days, and 4 = every day. The total POEM score is calculated by summing the score of each item resulting in a maximum of 28 and a minimum of 0, with higher values indicating severe disease | Week 16 | 
| Change From Baseline to Week 16 in 5-D Itch | The 5-D Itch Scale is a questionnaire consisting of 5 items used specifically to measure the course of itch by asking for the degree, duration, disability and distribution of the pruritus within the last 2 weeks. The scores from each item are summed, with maximum score of 25 and minimum score of 5. Higher score represent worse outcome | Week 16 | 
| Occurrence of Adverse Events | To assess the safety and tolerability of MEDI3506 compared with placebo, in adult subjects with moderate-to-severe AD. | up to 24 weeks | 
| Oral or Tympanic Temperature Taken During Vital Signs Assessment | Collectively with other vital signs assessment are used to assess the safety and tolerability of MEDI3506 compared with placebo, in adult subjects with moderate-to-severe AD. | Baseline, week 16 and week 24 | 
| Systolic Blood Pressure Taken During Vital Signs Assessment | Collectively with other vital signs assessment are used to assess the safety and tolerability of MEDI3506 compared with placebo, in adult subjects with moderate-to-severe AD. | Baseline, week 16 and week 24 | 
| Heart Rate Taken During Vital Signs Assessment | Collectively with other vital signs assessment are used to assess the safety and tolerability of MEDI3506 compared with placebo, in adult subjects with moderate-to-severe AD. | Baseline, week 16 and week 24 | 
| Respiratory Rate Collected During Vital Signs Assessment | Collectively with other vital signs assessment are used to assess the safety and tolerability of MEDI3506 compared with placebo, in adult subjects with moderate-to-severe AD. | Baseline, week 16 and week 24 | 
| Number of Participants With Abnormal Laboratory Assessments Relative to Normal Ranges for Haematology | To assess the safety and tolerability of MEDI3506 compared with placebo, in adult subjects with moderate-to-severe AD. | up to 24 weeks | 
| Number of Participants With Abnormal Laboratory Assessments Relative to Normal Ranges for Serum Chemistry | To assess the safety and tolerability of MEDI3506 compared with placebo, in adult subjects with moderate-to-severe AD. | up to 24 weeks | 
| Number of Participants With Abnormal Laboratory Assessments Relative to Normal Ranges for Urinalysis | To assess the safety and tolerability of MEDI3506 compared with placebo, in adult subjects with moderate-to-severe AD. | up to 24 weeks | 
| Heart Rate (Beats/Min) Recorded on ECGs | Collectively with other ECG parameters are used t assess the safety and tolerability of MEDI3506 compared with placebo, in adult subjects with moderate-to-severe AD. | Baseline, week 16 and week 24 | 
| QT (Miliseconds) Recorded on ECGs | Collectively with other ECG parameters are used to assess the safety and tolerability of MEDI3506 compared with placebo, in adult subjects with moderate-to-severe AD. | Baseline, week 16 and week 24 | 
| Number of Participants With Investigator's Overall ECGs Evaluations, e.g. Normal/Abnormal and Their Clinical Significance | Collectively with other ECG parameters are used to assess the safety and tolerability of MEDI3506 compared with placebo, in adult subjects with moderate-to-severe AD. | Week 16 and week 24 | 
| Left Ventricular Ejection Fraction Measured by Echocardiogram | To assess the safety and tolerability of MEDI3506 compared with placebo, in adult subjects with moderate-to-severe AD. | Baseline and week 16 | 
| Serum MEDI3506 Concentration Profiles | To evaluate the PK of MEDI3506 in adult subjects with moderate-to-severe AD. | Week 16 and week 24 | 
| Occurence of Anti-drug Antibody During the Treatment and Follow-up Periods | To evaluate the immunogenicity of MEDI3506 in adult subjects with moderate-to-severe AD. | up to 24 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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MEDI3506, Safety, Efficacy, Atopic Dermatitis, Eczema