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

Study identifier:D5240C00001

ClinicalTrials.gov identifier:NCT02525094

EudraCT identifier:N/A

CTIS identifier:N/A

Study Complete

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

Medical condition

Atopic Dermatitis

Phase

Phase 2

Healthy volunteers

Study drug

Sex

All

Actual Enrollment

113

Study type

Interventional

Age

18 Years - 75 Years

Date

Study Start Date: 15 Aug 2015

Primary Completion Date: 09 May 2016

Study Completion Date: 15 Jul 2016

Study design

Allocation: Randomized
Endpoint Classification: Safety/Efficacy
Intervention Model: Parallel Assignment
Masking: Double Blind
Primary Purpose: Treatment

Verification:

Verified 01 Dec 2018 by MedImmune, LLC

Collaborators

Amgen

Inclusion and exclusion criteria

Location

Research Site

Arlington Hts, IL, United States, 60005

Location

Research Site

Charlotte, NC, United States, 28277

Location

Research Site

Carmel, Indiana, United States, 46032

Location

Research Site

Barrie, ON, Canada, L4M 6L2

Location

Research Site

Tampa, FL, United States, 33624

Location

Research Site

Quebec, QC, Canada, G1V 4X7

Location

Research Site

Indianapolis, IN, United States, 46256

Location

Research Site

ACT, Australia, 02606

Arms	Assigned Interventions
Experimental: MEDI9929 280 mg Participants will receive 6 subcutaneous doses of MEDI9929 280 mg every 2 weeks for 12 weeks, with the last dose at Week 10.	Biological/Vaccine: MEDI9929 Participants will receive 6 subcutaneous doses of MEDI9929 280 mg every 2 weeks for 12 weeks, with the last dose at Week 10.
Placebo Comparator: Placebo Participants will receive 6 subcutaneous doses of placebo every 2 weeks for 12 weeks, with the last dose at Week 10.	Biological/Vaccine: Placebo Participants will receive 6 subcutaneous doses of placebo every 2 weeks for 12 weeks, with the last dose at Week 10.

Participant Flow

Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
The study was conducted from 15Aug2015 to 15Jul2016.

Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
A total of 155 participants were screened, of which 113 were randomized into the study.

Reporting Groups

	Description
Placebo	Participants received 6 subcutaneous doses of placebo every 2 weeks for 12 weeks (with the last dose at Week 10) and were followed up till Week 22. Additionally, the participants received maintenance therapy of Class 3 topical corticosteroids (TCS) cream or ointment for lesional skin from the start of the run-in period (Visit 2, Week -2) to Week 22.
MEDI9929 280 mg	Participants received 6 subcutaneous doses of MEDI9929 280 mg every 2 weeks for 12 weeks (with the last dose at Week 10) and were followed up till Week 22. Additionally, the participants received maintenance therapy of Class 3 topical corticosteroids (TCS) cream or ointment for lesional skin from the start of the run-in period (Visit 2, Week -2) to Week 22.

Participant Flow: Overall Study

	Placebo	MEDI9929 280 mg
STARTED	57	56
Treated	56	55
COMPLETED	49	48
NOT COMPLETED	8	8
Lost to Follow-up	2	1
Withdrawal by Subject	5	6
Not Treated	1	1

Baseline Characteristics

Analysis Population Description -- Explanation of how the number of participants for analysis was determined.

Intent-To-Treat (ITT) population included all participants who were randomized and received any study investigational product.

Reporting Groups

	Description
Placebo	Participants received 6 subcutaneous doses of placebo every 2 weeks for 12 weeks (with the last dose at Week 10) and were followed up till Week 22. Additionally, the participants received maintenance therapy of Class 3 topical corticosteroids (TCS) cream or ointment for lesional skin from the start of the run-in period (Visit 2, Week -2) to Week 22.
MEDI9929 280 mg	Participants received 6 subcutaneous doses of MEDI9929 280 mg every 2 weeks for 12 weeks (with the last dose at Week 10) and were followed up till Week 22. Additionally, the participants received maintenance therapy of Class 3 topical corticosteroids (TCS) cream or ointment for lesional skin from the start of the run-in period (Visit 2, Week -2) to Week 22.

Baseline Measures

	Placebo	MEDI9929 280 mg	Total
Number of Participants [units: Participants]	56	55	111
Age Continuous [units: Years] Mean ± Standard Deviation	38.8 ± 15.3	38.5 ± 14.9	38.7 ± 15.0
Age, Customized [units: Participants]
18-35 years	28	27	55
36-75 years	28	28	56
Gender, Male/Female [units: ]
Female	26	23	49
Male	30	32	62
Eczema Area and Severity Index Score ^[1] [units: Participants]
<= 25 points	36	33	69
> 25 points	20	22	42
Investigator's Global Assessment ^[2] [units: Participants]
Category 2	0	1	1
Category 3	46	44	90
Category 4	10	10	20
Atopic Dermatitis Status [units: Participants]
IgE >= 150 kU/L and Positive Serum Specific IgEa	50	47	97
IgE >= 150 kU/L and Negative Serum Specific IgE	2	0	2
IgE < 150 kU/L and Positive Serum Specific IgE	3	3	6
IgE < 150 kU/L and Negative Serum Specific IgEb	1	3	4
Missing	0	2	2

Outcome Measures

1. Primary Outcome Measure: 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 [ Time Frame: Baseline (Day 1) and Week 12 ]

Measure Type	Primary
Measure Name	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
Measure Description	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.
Time Frame	Baseline (Day 1) and Week 12
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Intent-To-Treat (ITT) population included all participants who were randomized and received any study investigational product.

Reporting Groups

	Description
Placebo	Participants received 6 subcutaneous doses of placebo every 2 weeks for 12 weeks (with the last dose at Week 10) and were followed up till Week 22. Additionally, the participants received maintenance therapy of Class 3 topical corticosteroids (TCS) cream or ointment for lesional skin from the start of the run-in period (Visit 2, Week -2) to Week 22.
MEDI9929 280 mg	Participants received 6 subcutaneous doses of MEDI9929 280 mg every 2 weeks for 12 weeks (with the last dose at Week 10) and were followed up till Week 22. Additionally, the participants received maintenance therapy of Class 3 topical corticosteroids (TCS) cream or ointment for lesional skin from the start of the run-in period (Visit 2, Week -2) to Week 22.

Measured Values

	Placebo	MEDI9929 280 mg
Number of Participants Analyzed [units:participants]	56	55
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 [units: Percentage of participants]	48.2	64.7

Statistical Analysis 1 for 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

Groups^[1]	All groups
Odds Ratio (OR)^[5]	1.97
95% Confidence Interval	( 0.90 to 4.33 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[5]	Other relevant estimation information:
	No text entered.

2. Secondary Outcome Measure: Percentage of Participants Achieving >= 75 % Reduction From Baseline in EASI75 at Week 12 [ Time Frame: Baseline (Day 1) and Week 12 ]

Measure Type	Secondary
Measure Name	Percentage of Participants Achieving >= 75 % Reduction From Baseline in EASI75 at Week 12
Measure Description	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.
Time Frame	Baseline (Day 1) and Week 12
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
ITT population included all participants who were randomized and received any study investigational product.

Reporting Groups

	Description
Placebo	Participants received 6 subcutaneous doses of placebo every 2 weeks for 12 weeks (with the last dose at Week 10) and were followed up till Week 22. Additionally, the participants received maintenance therapy of Class 3 topical corticosteroids (TCS) cream or ointment for lesional skin from the start of the run-in period (Visit 2, Week -2) to Week 22.
MEDI9929 280 mg	Participants received 6 subcutaneous doses of MEDI9929 280 mg every 2 weeks for 12 weeks (with the last dose at Week 10) and were followed up till Week 22. Additionally, the participants received maintenance therapy of Class 3 topical corticosteroids (TCS) cream or ointment for lesional skin from the start of the run-in period (Visit 2, Week -2) to Week 22.

Measured Values

	Placebo	MEDI9929 280 mg
Number of Participants Analyzed [units:participants]	56	55
Percentage of Participants Achieving >= 75 % Reduction From Baseline in EASI75 at Week 12 [units: Percentage of participants]	19.8	24.4

No statistical analysis provided for Percentage of Participants Achieving >= 75 % Reduction From Baseline in EASI75 at Week 12

3. Secondary Outcome Measure: Mean Change From Baseline in EASI Total Score at Week 12 [ Time Frame: Baseline (Day 1) and Week 12 ]

Measure Type	Secondary
Measure Name	Mean Change From Baseline in EASI Total Score at Week 12
Measure Description	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.
Time Frame	Baseline (Day 1) and Week 12
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
ITT population included all participants who were randomized and received any study investigational product.

Reporting Groups

	Description
Placebo	Participants received 6 subcutaneous doses of placebo every 2 weeks for 12 weeks (with the last dose at Week 10) and were followed up till Week 22. Additionally, the participants received maintenance therapy of Class 3 topical corticosteroids (TCS) cream or ointment for lesional skin from the start of the run-in period (Visit 2, Week -2) to Week 22.
MEDI9929 280 mg	Participants received 6 subcutaneous doses of MEDI9929 280 mg every 2 weeks for 12 weeks (with the last dose at Week 10) and were followed up till Week 22. Additionally, the participants received maintenance therapy of Class 3 topical corticosteroids (TCS) cream or ointment for lesional skin from the start of the run-in period (Visit 2, Week -2) to Week 22.

Measured Values

	Placebo	MEDI9929 280 mg
Number of Participants Analyzed [units:participants]	56	55
Mean Change From Baseline in EASI Total Score at Week 12 [units: units on a scale] Mean (Standard Deviation)
Baseline	24.48 (11.21)	24.05 (12.38)
Week 12	-11.23 (8.73)	-12.16 (9.96)

No statistical analysis provided for Mean Change From Baseline in EASI Total Score at Week 12

4. Secondary Outcome Measure: 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 [ Time Frame: Baseline (Day 1) and Week 12 ]

Measure Type	Secondary
Measure Name	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
Measure Description	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.
Time Frame	Baseline (Day 1) and Week 12
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
ITT population included all participants who were randomized and received any study investigational product.

Reporting Groups

	Description
Placebo	Participants received 6 subcutaneous doses of placebo every 2 weeks for 12 weeks (with the last dose at Week 10) and were followed up till Week 22. Additionally, the participants received maintenance therapy of Class 3 topical corticosteroids (TCS) cream or ointment for lesional skin from the start of the run-in period (Visit 2, Week -2) to Week 22.
MEDI9929 280 mg	Participants received 6 subcutaneous doses of MEDI9929 280 mg every 2 weeks for 12 weeks (with the last dose at Week 10) and were followed up till Week 22. Additionally, the participants received maintenance therapy of Class 3 topical corticosteroids (TCS) cream or ointment for lesional skin from the start of the run-in period (Visit 2, Week -2) to Week 22.

Measured Values

	Placebo	MEDI9929 280 mg
Number of Participants Analyzed [units:participants]	56	55
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 [units: Percentage of participants]	12.8	19.3

No statistical analysis provided for 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

5. Secondary Outcome Measure: Mean Change From Baseline in the Scoring of Atopic Dermatitis (SCORAD) at Week 12 [ Time Frame: Baseline (Day 1) and Week 12 ]

Measure Type	Secondary
Measure Name	Mean Change From Baseline in the Scoring of Atopic Dermatitis (SCORAD) at Week 12
Measure Description	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.
Time Frame	Baseline (Day 1) and Week 12
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
ITT population included all participants who were randomized and received any study investigational product.

Reporting Groups

	Description
Placebo	Participants received 6 subcutaneous doses of placebo every 2 weeks for 12 weeks (with the last dose at Week 10) and were followed up till Week 22. Additionally, the participants received maintenance therapy of Class 3 topical corticosteroids (TCS) cream or ointment for lesional skin from the start of the run-in period (Visit 2, Week -2) to Week 22.
MEDI9929 280 mg	Participants received 6 subcutaneous doses of MEDI9929 280 mg every 2 weeks for 12 weeks (with the last dose at Week 10) and were followed up till Week 22. Additionally, the participants received maintenance therapy of Class 3 topical corticosteroids (TCS) cream or ointment for lesional skin from the start of the run-in period (Visit 2, Week -2) to Week 22.

Measured Values

	Placebo	MEDI9929 280 mg
Number of Participants Analyzed [units:participants]	56	55
Mean Change From Baseline in the Scoring of Atopic Dermatitis (SCORAD) at Week 12 [units: units on a scale] Mean (Standard Deviation)
Baseline	58.66 (13.32)	57.68 (14.80)
Week 12	-19.35 (17.49)	-24.24 (16.94)

No statistical analysis provided for Mean Change From Baseline in the Scoring of Atopic Dermatitis (SCORAD) at Week 12

6. Secondary Outcome Measure: Percentage of Participants Achieving >= 50% Reduction From Baseline in SCORAD 50 [ Time Frame: Baseline (Day 1) and Week 12 ]

Measure Type	Secondary
Measure Name	Percentage of Participants Achieving >= 50% Reduction From Baseline in SCORAD 50
Measure Description	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.
Time Frame	Baseline (Day 1) and Week 12
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
ITT population included all participants who were randomized and received any study investigational product.

Reporting Groups

	Description
Placebo	Participants received 6 subcutaneous doses of placebo every 2 weeks for 12 weeks (with the last dose at Week 10) and were followed up till Week 22. Additionally, the participants received maintenance therapy of Class 3 topical corticosteroids (TCS) cream or ointment for lesional skin from the start of the run-in period (Visit 2, Week -2) to Week 22.
MEDI9929 280 mg	Participants received 6 subcutaneous doses of MEDI9929 280 mg every 2 weeks for 12 weeks (with the last dose at Week 10) and were followed up till Week 22. Additionally, the participants received maintenance therapy of Class 3 topical corticosteroids (TCS) cream or ointment for lesional skin from the start of the run-in period (Visit 2, Week -2) to Week 22.

Measured Values

	Placebo	MEDI9929 280 mg
Number of Participants Analyzed [units:participants]	56	55
Percentage of Participants Achieving >= 50% Reduction From Baseline in SCORAD 50 [units: Percentage of participants]	29.4	41.0

No statistical analysis provided for Percentage of Participants Achieving >= 50% Reduction From Baseline in SCORAD 50

7. Secondary Outcome Measure: Percentage of Participants Achieving >= 75% Reduction From Baseline in SCORAD 75 [ Time Frame: Baseline (Day 1) and Week 12 ]

Measure Type	Secondary
Measure Name	Percentage of Participants Achieving >= 75% Reduction From Baseline in SCORAD 75
Measure Description	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.
Time Frame	Baseline (Day 1) and Week 12
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
ITT population included all participants who were randomized and received any study investigational product.

Reporting Groups

	Description
Placebo	Participants received 6 subcutaneous doses of placebo every 2 weeks for 12 weeks (with the last dose at Week 10) and were followed up till Week 22. Additionally, the participants received maintenance therapy of Class 3 topical corticosteroids (TCS) cream or ointment for lesional skin from the start of the run-in period (Visit 2, Week -2) to Week 22.
MEDI9929 280 mg	Participants received 6 subcutaneous doses of MEDI9929 280 mg every 2 weeks for 12 weeks (with the last dose at Week 10) and were followed up till Week 22. Additionally, the participants received maintenance therapy of Class 3 topical corticosteroids (TCS) cream or ointment for lesional skin from the start of the run-in period (Visit 2, Week -2) to Week 22.

Measured Values

	Placebo	MEDI9929 280 mg
Number of Participants Analyzed [units:participants]	56	55
Percentage of Participants Achieving >= 75% Reduction From Baseline in SCORAD 75 [units: Percentage of participants]	7.4	9.8

No statistical analysis provided for Percentage of Participants Achieving >= 75% Reduction From Baseline in SCORAD 75

8. Secondary Outcome Measure: Mean Change from Baseline in Average Pruritus Numeric Rating Scale (NRS) at Week 12 [ Time Frame: Baseline (Day 1) and Week 12 ]

Measure Type	Secondary
Measure Name	Mean Change from Baseline in Average Pruritus Numeric Rating Scale (NRS) at Week 12
Measure Description	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.
Time Frame	Baseline (Day 1) and Week 12
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
ITT population included all participants who were randomized and received any study investigational product.

Reporting Groups

	Description
Placebo	Participants received 6 subcutaneous doses of placebo every 2 weeks for 12 weeks (with the last dose at Week 10) and were followed up till Week 22. Additionally, the participants received maintenance therapy of Class 3 topical corticosteroids (TCS) cream or ointment for lesional skin from the start of the run-in period (Visit 2, Week -2) to Week 22.
MEDI9929 280 mg	Participants received 6 subcutaneous doses of MEDI9929 280 mg every 2 weeks for 12 weeks (with the last dose at Week 10) and were followed up till Week 22. Additionally, the participants received maintenance therapy of Class 3 topical corticosteroids (TCS) cream or ointment for lesional skin from the start of the run-in period (Visit 2, Week -2) to Week 22.

Measured Values

	Placebo	MEDI9929 280 mg
Number of Participants Analyzed [units:participants]	56	55
Mean Change from Baseline in Average Pruritus Numeric Rating Scale (NRS) at Week 12 [units: units on a scale] Mean (Standard Deviation)
Baseline	5.15 (2.10)	5.26 (2.02)
Week 12	-1.39 (1.93)	-1.90 (1.99)

No statistical analysis provided for Mean Change from Baseline in Average Pruritus Numeric Rating Scale (NRS) at Week 12

9. Secondary Outcome Measure: Mean Change from Baseline in 5-D Pruritus Score at Week 12 [ Time Frame: Baseline (Day 1) and Week 12 ]

Measure Type	Secondary
Measure Name	Mean Change from Baseline in 5-D Pruritus Score at Week 12
Measure Description	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.
Time Frame	Baseline (Day 1) and Week 12
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
ITT population included all participants who were randomized and received any study investigational product.

Reporting Groups

	Description
Placebo	Participants received 6 subcutaneous doses of placebo every 2 weeks for 12 weeks (with the last dose at Week 10) and were followed up till Week 22. Additionally, the participants received maintenance therapy of Class 3 topical corticosteroids (TCS) cream or ointment for lesional skin from the start of the run-in period (Visit 2, Week -2) to Week 22.
MEDI9929 280 mg	Participants received 6 subcutaneous doses of MEDI9929 280 mg every 2 weeks for 12 weeks (with the last dose at Week 10) and were followed up till Week 22. Additionally, the participants received maintenance therapy of Class 3 topical corticosteroids (TCS) cream or ointment for lesional skin from the start of the run-in period (Visit 2, Week -2) to Week 22.

Measured Values

	Placebo	MEDI9929 280 mg
Number of Participants Analyzed [units:participants]	56	55
Mean Change from Baseline in 5-D Pruritus Score at Week 12 [units: units on a scale] Mean (Standard Deviation)
Baseline	16.7 (3.7)	16.0 (3.7)
Week 12	-3.9 (4.5)	-3.6 (4.4)

No statistical analysis provided for Mean Change from Baseline in 5-D Pruritus Score at Week 12

10. Secondary Outcome Measure: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) [ Time Frame: From treatment administration (Day1) to 22 weeks ]

Measure Type	Secondary
Measure Name	Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs)
Measure Description	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.
Time Frame	From treatment administration (Day1) to 22 weeks
Safety Issue?	Yes

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
As-treated population included all participants who received any study drug. Participants who received at least one dose of MEDI9929 during study, regardless of randomized treatment assignment, were analyzed under MEDI9929. One participant who randomized to placebo but received an incorrect first dose of MEDI9929 was included in "MEDI9929" group.

Reporting Groups

	Description
Placebo	Participants received 6 subcutaneous doses of placebo every 2 weeks for 12 weeks (with the last dose at Week 10) and were followed up till Week 22. Additionally, the participants received maintenance therapy of Class 3 topical corticosteroids (TCS) cream or ointment for lesional skin from the start of the run-in period (Visit 2, Week -2) to Week 22.
MEDI9929 280 mg	Participants received 6 subcutaneous doses of MEDI9929 280 mg every 2 weeks for 12 weeks (with the last dose at Week 10) and were followed up till Week 22. Additionally, the participants received maintenance therapy of Class 3 topical corticosteroids (TCS) cream or ointment for lesional skin from the start of the run-in period (Visit 2, Week -2) to Week 22.

Measured Values

	Placebo	MEDI9929 280 mg
Number of Participants Analyzed [units:participants]	55	56
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) [units: Participants]
TEAEs	40	38
TESAEs	3	2

No statistical analysis provided for Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs)

11. Secondary Outcome Measure: Mean Trough Serum Concentration of MEDI9929 [ Time Frame: Week 0 (Pre dose), Weeks 4, 8, and 12 (post dose) ]

Measure Type	Secondary
Measure Name	Mean Trough Serum Concentration of MEDI9929
Measure Description	The mean serum concentrations of MEDI9929 was observed at specified timepoints.
Time Frame	Week 0 (Pre dose), Weeks 4, 8, and 12 (post dose)
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
PK population included all participants who received MEDI9929 and had a sufficient number of serum concentration measurements for computing PK parameters.

Reporting Groups

	Description
MEDI9929 280 mg	Participants received 6 subcutaneous doses of MEDI9929 280 mg every 2 weeks for 12 weeks (with the last dose at Week 10) and were followed up till Week 22. Additionally, the participants received maintenance therapy of Class 3 topical corticosteroids (TCS) cream or ointment for lesional skin from the start of the run-in period (Visit 2, Week -2) to Week 22.

Measured Values

	MEDI9929 280 mg
Number of Participants Analyzed [units:participants]	55
Mean Trough Serum Concentration of MEDI9929 [units: mcg/mL] Mean (Standard Deviation)
Week 0	NA (NA)^[1]
Week 4	34.7 (10.9)
Week 8	50.5 (17.5)
Week 12	54.9 (21.5)

No statistical analysis provided for Mean Trough Serum Concentration of MEDI9929

12. Secondary Outcome Measure: Number of Participants who Developed Detectable MEDI9929 Anti-drug Antibodies [ Time Frame: Baseline (Day 1) to Week 22 ]

Measure Type	Secondary
Measure Name	Number of Participants who Developed Detectable MEDI9929 Anti-drug Antibodies
Measure Description	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.
Time Frame	Baseline (Day 1) to Week 22
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
ITT population included all participants who were randomized and received any study investigational product.

Reporting Groups

	Description
Placebo	Participants received 6 subcutaneous doses of placebo every 2 weeks for 12 weeks (with the last dose at Week 10) and were followed up till Week 22. Additionally, the participants received maintenance therapy of Class 3 topical corticosteroids (TCS) cream or ointment for lesional skin from the start of the run-in period (Visit 2, Week -2) to Week 22.
MEDI9929 280 mg	Participants received 6 subcutaneous doses of MEDI9929 280 mg every 2 weeks for 12 weeks (with the last dose at Week 10) and were followed up till Week 22. Additionally, the participants received maintenance therapy of Class 3 topical corticosteroids (TCS) cream or ointment for lesional skin from the start of the run-in period (Visit 2, Week -2) to Week 22.

Measured Values

	Placebo	MEDI9929 280 mg
Number of Participants Analyzed [units:participants]	56	55
Number of Participants who Developed Detectable MEDI9929 Anti-drug Antibodies [units: Participants]
Baseline	2	1
Week 22	2	0

No statistical analysis provided for Number of Participants who Developed Detectable MEDI9929 Anti-drug Antibodies

Serious Adverse Events

Time Frame	From treatment administration (Day1) to 22 weeks
Additional Description	AEs were reported for As-treated population, which included all participants who received any study drug. Participants who received at least one dose of MEDI9929, regardless of randomized treatment, were analyzed under MEDI9929. One participant who randomized to placebo but received an incorrect first dose of MEDI9929 was included in MEDI9929 group

Reporting Groups

	Description
Placebo	Participants received 6 subcutaneous doses of placebo every 2 weeks for 12 weeks (with the last dose at Week 10) and were followed up till Week 22. Additionally, the participants received maintenance therapy of Class 3 topical corticosteroids (TCS) cream or ointment for lesional skin from the start of the run-in period (Visit 2, Week -2) to Week 22.
MEDI9929 280 mg	Participants received 6 subcutaneous doses of MEDI9929 280 mg every 2 weeks for 12 weeks (with the last dose at Week 10) and were followed up till Week 22. Additionally, the participants received maintenance therapy of Class 3 topical corticosteroids (TCS) cream or ointment for lesional skin from the start of the run-in period (Visit 2, Week -2) to Week 22.

Serious Adverse Events

Placebo

MEDI9929 280 mg

Total, serious adverse events

# participants affected / at risk

3/55 (5.45%)

2/56 (3.57%)

General disorders and administration site conditions

Chest pain¹,^†

# participants affected / at risk

1/55 (1.82%)

0/56 (0.00%)

# events

Infections and infestations

Cellulitis¹,^†

# participants affected / at risk

1/55 (1.82%)

0/56 (0.00%)

# events

Infections and infestations

Infected dermal cyst¹,^†

# participants affected / at risk

0/55 (0.00%)

1/56 (1.79%)

# events

Nervous system disorders

Syncope¹,^†

# participants affected / at risk

1/55 (1.82%)

0/56 (0.00%)

# events

Skin and subcutaneous tissue disorders

Dermatitis atopic¹,^†

# participants affected / at risk

1/55 (1.82%)

1/56 (1.79%)

# events

†	Events were collected by systematic assessment
1	Term from vocabulary, MedDRA 19.0

Other Adverse Events

Time Frame	From treatment administration (Day1) to 22 weeks
Additional Description	AEs were reported for As-treated population, which included all participants who received any study drug. Participants who received at least one dose of MEDI9929, regardless of randomized treatment, were analyzed under MEDI9929. One participant who randomized to placebo but received an incorrect first dose of MEDI9929 was included in MEDI9929 group

Frequency Threshold

Threshold above which other adverse events are reported	1%

Reporting Groups

	Description
Placebo	Participants received 6 subcutaneous doses of placebo every 2 weeks for 12 weeks (with the last dose at Week 10) and were followed up till Week 22. Additionally, the participants received maintenance therapy of Class 3 topical corticosteroids (TCS) cream or ointment for lesional skin from the start of the run-in period (Visit 2, Week -2) to Week 22.
MEDI9929 280 mg	Participants received 6 subcutaneous doses of MEDI9929 280 mg every 2 weeks for 12 weeks (with the last dose at Week 10) and were followed up till Week 22. Additionally, the participants received maintenance therapy of Class 3 topical corticosteroids (TCS) cream or ointment for lesional skin from the start of the run-in period (Visit 2, Week -2) to Week 22.

Other Adverse Events

Placebo

MEDI9929 280 mg

Total, other (not including serious) adverse events

# participants affected / at risk

33/55 (60.00%)

29/56 (51.79%)

Gastrointestinal disorders

Abdominal pain¹,^†

# participants affected / at risk

0/55 (0.00%)

2/56 (3.57%)

# events

Gastrointestinal disorders

Diarrhoea¹,^†

# participants affected / at risk

3/55 (5.45%)

5/56 (8.93%)

# events

General disorders and administration site conditions

Influenza like illness¹,^†

# participants affected / at risk

0/55 (0.00%)

2/56 (3.57%)

# events

General disorders and administration site conditions

Injection site erythema¹,^†

# participants affected / at risk

0/55 (0.00%)

3/56 (5.36%)

# events

Immune system disorders

Food allergy¹,^†

# participants affected / at risk

0/55 (0.00%)

2/56 (3.57%)

# events

Infections and infestations

Cellulitis¹,^†

# participants affected / at risk

2/55 (3.64%)

0/56 (0.00%)

# events

Infections and infestations

Conjunctivitis¹,^†

# participants affected / at risk

1/55 (1.82%)

1/56 (1.79%)

# events

Infections and infestations

Folliculitis¹,^†

# participants affected / at risk

1/55 (1.82%)

1/56 (1.79%)

# events

Infections and infestations

Herpes simplex¹,^†

# participants affected / at risk

1/55 (1.82%)

1/56 (1.79%)

# events

Infections and infestations

Nasopharyngitis¹,^†

# participants affected / at risk

11/55 (20.00%)

13/56 (23.21%)

# events

Infections and infestations

Sinusitis¹,^†

# participants affected / at risk

2/55 (3.64%)

2/56 (3.57%)

# events

Infections and infestations

Upper respiratory tract infection¹,^†

# participants affected / at risk

7/55 (12.73%)

1/56 (1.79%)

# events

Infections and infestations

Urinary tract infection¹,^†

# participants affected / at risk

1/55 (1.82%)

1/56 (1.79%)

# events

Musculoskeletal and connective tissue disorders

Arthralgia¹,^†

# participants affected / at risk

2/55 (3.64%)

1/56 (1.79%)

# events

Musculoskeletal and connective tissue disorders

Muscle spasms¹,^†

# participants affected / at risk

1/55 (1.82%)

1/56 (1.79%)

# events

Musculoskeletal and connective tissue disorders

Musculoskeletal pain¹,^†

# participants affected / at risk

0/55 (0.00%)

2/56 (3.57%)

# events

Musculoskeletal and connective tissue disorders

Myalgia¹,^†

# participants affected / at risk

0/55 (0.00%)

2/56 (3.57%)

# events

Nervous system disorders

Headache¹,^†

# participants affected / at risk

1/55 (1.82%)

3/56 (5.36%)

# events

Respiratory, thoracic and mediastinal disorders

Oropharyngeal pain¹,^†

# participants affected / at risk

0/55 (0.00%)

2/56 (3.57%)

# events

Skin and subcutaneous tissue disorders

Dermatitis atopic¹,^†

# participants affected / at risk

7/55 (12.73%)

5/56 (8.93%)

# events

Skin and subcutaneous tissue disorders

Pruritus¹,^†

# participants affected / at risk

1/55 (1.82%)

1/56 (1.79%)

# events

Skin and subcutaneous tissue disorders

Rash¹,^†

# participants affected / at risk

2/55 (3.64%)

0/56 (0.00%)

# events

†	Events were collected by systematic assessment
1	Term from vocabulary, MedDRA 19.0

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

The agreement is:

	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days . The sponsor cannot require changes to the communication and cannot extend the embargo.
	Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed. Restriction Description: MedImmune has 60 days to review results communications prior to public release and may delete information that compromises on-going studies or is considered proprietary. This restriction is not intended to compromise the objective scientific integrity of the manuscript, it being understood that results shall be published regardless of outcome.

Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
No text entered.

Results Point of Contact

Name/Title:	Rene van der Merwe
Organization:	MedImmune, LLC
Phone	301-398-2532
E-mail:	[email protected]

Documents available

D5240C00001 NCT02525094 Simpson_ALLEVIAD_JAAD_supplementary
Download
Trial Results Summaries
Available here

Contacts

Contact

AstraZeneca Clinical Study Information Center

1-877-240-9479

information.center@astrazeneca.com

Investigators

Principal Investigator

Eric Simpson

Oregon Health & Science University

Sponsors

Collaborators

Inclusion Criteria

Exclusion Criteria

Research Site

Research Site

Research Site

Research Site

Research Site

Research Site

Research Site

Research Site

D5240C00001 NCT02525094 Simpson_ALLEVIAD_JAAD_supplementary

Trial Results Summaries