Clinical trial NCT03055195: Efficacy and Safety Study of Mepolizumab in Subjects With Moderate to Severe Atopic Dermatitis
Official title: Study 205050: A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study to Investigate the Efficacy and Safety of Mepolizumab Administered Subcutaneously in Subjects With Moderate to Severe Atopic Dermatitis
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Dermatitis, Atopic
Keywords: subcutaneous
safety
mepolizumab
efficacy
atopic dermatitis
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2017-02-16
Enrollment: 34
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Mepolizumab is a humanized Immunoglobulin G1 (IgG1) monoclonal antibody (mAb) that acts on Interleukin-5 (IL-5), which is responsible for the growth and differentiation, recruitment, activation, and survival of eosinophils; thereby reducing the production and survival of eosinophils which may be therapeutic in subjects with atopic dermatitis (AD). This study will investigate the efficacy and safety of mepolizumab (100 milligram \[mg\] subcutaneous \[SC\] administered every 4 weeks) compared with placebo in adult subjects with moderate to severe atopic dermatitis (AD). Subjects will be randomized 1:1 to either placebo SC or mepolizumab SC. The study will comprise of a pre-screening period of up to approximately 4 weeks, a screening period of up to 2 weeks, followed by a 16-Week study treatment period (16 weeks with the last dose of study treatment at Week 12) and follow-up period of up to 4-week. The total duration of subject participation will be approximately 26 weeks. (Note: For subjects, who may need to stop treatment with a biologic, the total Pre-Screening and Screening period may last up to 20 weeks and total duration of participation in the study may be up to 40 weeks).


Eligibility criteria: Inclusion Criteria

* Age between 18 and 70 years of age inclusive, at the time of signing the informed consent.
* AD diagnosed by the Eichenfield revised criteria of Hanifin and Rajka.
* Diagnosis of AD \>=2 years prior to the Screening visit.
* An IGA score \>=3 at the Screening and Baseline visits.
* AD involvement of \>=10% body surface area at the Screening and Baseline visits.
* EASI score \>=16 at the Screening and Baseline visits.
* Absolute blood eosinophil count \>=350 cells/microliter at the Screening visit.
* Applied the same non-prescription, non-medicated (without an active ingredient) emollient twice daily for at least 7 days immediately before the Baseline visit.
* Recent history (\<=6 months prior to the Screening visit) of inadequate response to a stable regimen of prescription topical medication or for whom prescription topical medications are not tolerated or where there is a concern for potential side effects, such as skin thinning or increased risk of hypothalamic-pituitary-adrenal \[HPA\] suppression; as well as, inadequate response to optimization of non-pharmacological measures such as moisturizers. Inadequate response to a stable regimen of prescription topical medication (such as medium to high potency topical corticosteroids or topical calcineurin inhibitors) is defined as failure to achieve and maintain remission or low disease activity state (equivalent to an IGA score =0 \[clear\] to 2 \[mild\]) despite treatment for the recommended duration as per label or for the maximum duration recommended for the subject treatment, whichever is shorter.
* Male or female: A female subject is eligible to participate if she is not pregnant (as confirmed by a negative urine human chorionic gonadotrophin (hCG) test), not lactating, and at least one of the following conditions: Non-reproductive potential- Pre-menopausal females with documented tubal ligation, documented hysteroscopic tubal occlusion procedure with follow-up confirmation of bilateral tubal occlusion, hysterectomy, documented bilateral oophorectomy; and postmenopausal defined as 12 months of spontaneous amenorrhea (in questionable cases a blood sample with simultaneous follicle stimulating hormone \[FSH\] and estradiol levels consistent with menopause). Females on hormone replacement therapy (HRT) and whose menopausal status is in doubt will be required to use one of the highly effective contraception methods if they wish to continue their HRT during the study. Otherwise, they must discontinue HRT to allow confirmation of post-menopausal status prior to study enrolment. Reproductive potential and agrees to follow one of the options listed in the Modified List of Highly Effective Methods for Avoiding Pregnancy in Females of Reproductive Potential (FRP) from 30 days prior to the first dose of study medication and until 16 weeks after the last dose of study medication.
* The investigator is responsible for ensuring that subjects understand how to properly use these methods of contraception.
* Subject is able to give signed informed consent that includes compliance with the requirements and restrictions listed in the consent form and in this protocol.

Exclusion Criteria

* Other types of eczema.
* Any other concomitant skin disorder (e.g., generalized erythroderma such as Netherton's Syndrome, or psoriasis), pigmentation, or extensive scarring that in the opinion of the investigator may interfere with the evaluation of AD lesions or compromise subject safety.
* Immunocompromised (e.g., lymphoma, acquired immunodeficiency syndrome, Wiskott-Aldrich Syndrome) or has a history of malignant disease within 5 years before the Baseline visit. Note: Subjects with successfully treated basal cell carcinoma (no more than 3 lesions), squamous cell carcinoma of the skin, or cervical carcinoma in situ, with no evidence of recurrence within the 3 years prior to the Baseline visit may participate in the study.
* A positive history for human immunodeficiency virus (HIV) antibody.
* Chronic or acute infection requiring treatment with oral or intravenous (IV) antibiotics, antivirals, anti-protozoals, or antifungals within 4 weeks before the Screening visit or anytime between the Screening and Baseline visits.
* Superficial skin infections within 1 week before the Screening visit.
* Known, pre-existing or suspected parasitic infection within 6 months before the Screening visit.
* Other known or suspected conditions that could lead to elevated eosinophils, for example, hypereosinophilic syndromes including eosinophilic granulomatosis with polyangiitis (EGPA, also known as Churg-Strauss Syndrome), eosinophilic esophagitis, or severe asthma.
* A history or ongoing serious illness or medical, physical, or psychiatric condition(s) that, in the investigator's opinion, may interfere with the subject's completion of the study.
* ALT \>2x upper limit of normal (ULN)
* Bilirubin \>1.5x ULN (isolated bilirubin \>1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin \<35%).
* Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
* QT Interval Corrected by Fridericia Correction Formula (QTcF) \>450 milliseconds (msec) or QTcF \>480 msec in subjects with Bundle Branch Block.
* Clinically significant abnormality in the hematological or biochemical screen, as judged by the investigator.
* Previously treated with mepolizumab or participated in a previous mepolizumab clinical study.
* Prior treatment with any of the medications or treatments listed in Table 1 within the indicated periods before the Screening visit.
* Prolonged exposure to natural (e.g, sunlight) ultraviolet (UV) radiation within 4 weeks prior to the Baseline visit and/or intention to have such exposure during the study, which is thought by the investigator to potentially impact the subject's AD.
* More than 2 visits per week to a tanning booth or parlor in the 4 weeks prior to the Baseline visit.
* Onset of a new exercise routine or major change to a previous exercise routine within 2 weeks before randomization, or unwilling to maintain current level of physical activity throughout the length of participation in this study.
* History of alcohol or other substance abuse within the last 2 years.
* Hypersensitivity to mepolizumab or any of its excipients.
* Presence of hepatitis B surface antigen (HBsAg), positive hepatitis C antibody test result at screening or within 3 months prior to first dose of study treatment.
* Exposure to more than 4 investigational medicinal products within 12 months prior to the Baseline visit.
* Subject is a member of the investigational team or his/her immediate family.

Primary outcomes:
measure: Number of Participants With an Investigator's Global Assessment (IGA) Score of 0 or 1 and at Least a 2- Grade Improvement at Week 16
timeFrame: Week 16
Secondary outcomes:
measure: Mean Percentage Change in Eczema Area and Severity Index (EASI) Score From Baseline to Each Study Visit
timeFrame: Baseline (Day 1) and Weeks 4, 8, 12, 16 and 20
measure: Number of Participants With an IGA Score of 0 or 1 and at Least a 2-grade Improvement at Each Study Visit
timeFrame: Weeks 4, 8, 12, 16 and 20
measure: Number of Participants With On-treatment Adverse Events (AEs), Serious Adverse Events (SAEs) and Non-serious Adverse Events (nSAEs)
timeFrame: Up to Week 20
measure: Number of Participants With On-treatment AEs of Special Interest Reported as Local Site Injection Reaction and Systemic Reactions
timeFrame: Up to Week 20
measure: Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils and Platelets
timeFrame: Baseline (Day 1) and Weeks 4, 8, 12, 16 and 20
measure: Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Hemoglobin
timeFrame: Baseline (Day 1) and Weeks 4, 8, 12, 16 and 20
measure: Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Volume
timeFrame: Baseline (Day 1) and Weeks 4, 8, 12, 16 and 20
measure: Change From Baseline in Hematology Parameter: Erythrocytes
timeFrame: Baseline (Day 1) and Weeks 4, 8, 12, 16 and 20
measure: Change From Baseline in Hematology Parameter: Hematocrit
timeFrame: Baseline (Day 1) and Weeks 4, 8, 12, 16 and 20
measure: Change From Baseline in Hematology Parameter: Hemoglobin
timeFrame: Baseline (Day 1) and Weeks 4, 8, 12, 16 and 20
measure: Change From Baseline in Chemistry Parameters: Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST)
timeFrame: Baseline (Day 1) and Weeks 4, 8, 12, and 16
measure: Change From Baseline in Chemistry Parameters: Albumin and Protein
timeFrame: Baseline (Day 1) and Weeks 4, 8, 12, and 16
measure: Change From Baseline in Chemistry Parameters: Bilirubin, Creatinine, Direct Bilirubin
timeFrame: Baseline (Day 1) and Weeks 4, 8, 12, and 16
measure: Change From Baseline in Chemistry Parameters: Calcium, Glucose, Potassium, Sodium and Urea
timeFrame: Baseline (Day 1) and Weeks 4, 8, 12, and 16
measure: Number of Participants With Worst Post Baseline Potential Clinical Importance (PCI) Value for Hematology Parameters
timeFrame: Up to Week 20
measure: Number of Participants With Worst Post Baseline PCI Value for Chemistry Parameters
timeFrame: Up to Week 16
measure: Change From Baseline in PR Interval, QRS Duration, QT Interval and QT Interval Corrected for Heart Rate According to Fridericia's Formula (QTcF)
timeFrame: Baseline (Screening) and Weeks 4, 16
measure: Change From Baseline in Vital Signs: Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP)
timeFrame: Baseline (Day 1) and Weeks 4, 8, 12, 16 and 20
measure: Change From Baseline in Vital Signs: Pulse Rate
timeFrame: Baseline (Day 1) and Weeks 4, 8, 12, 16 and 20
measure: Change From Baseline in Vital Signs: Temperature
timeFrame: Baseline (Day 1) and Weeks 4, 8, 12, 16 and 20
measure: Number of Participants With Worst Post Baseline PCI Value for Vital Signs
timeFrame: Up to Week 20
measure: Number of Participants With Abnormal Findings for ECG Parameters
timeFrame: Week 4 and Week 16
measure: Number of Participants With Any Time Post Baseline Anti-mepolizumab Binding Antibodies and Neutralizing Antibodies Response
timeFrame: Up to Week 20
Other outcomes:
Locations:
city: Fort Smith
country: United States
facility: GSK Investigational Site
state: Arkansas
city: Fremont
country: United States
facility: GSK Investigational Site
state: California
city: Santa Ana
country: United States
facility: GSK Investigational Site
state: California
city: Sandy Springs
country: United States
facility: GSK Investigational Site
state: Georgia
city: Chicago
country: United States
facility: GSK Investigational Site
state: Illinois
city: Indianapolis
country: United States
facility: GSK Investigational Site
state: Indiana
city: New Albany
country: United States
facility: GSK Investigational Site
state: Indiana
city: Louisville
country: United States
facility: GSK Investigational Site
state: Kentucky
city: Pittsburgh
country: United States
facility: GSK Investigational Site
state: Pennsylvania
city: San Antonio
country: United States
facility: GSK Investigational Site
state: Texas
city: Norfolk
country: United States
facility: GSK Investigational Site
state: Virginia
city: Surrey
country: Canada
facility: GSK Investigational Site
state: British Columbia
city: Vancouver
country: Canada
facility: GSK Investigational Site
state: British Columbia
city: Barrie
country: Canada
facility: GSK Investigational Site
state: Ontario
city: Markham
country: Canada
facility: GSK Investigational Site
state: Ontario
city: Oakville
country: Canada
facility: GSK Investigational Site
state: Ontario
city: Ottawa
country: Canada
facility: GSK Investigational Site
state: Ontario
city: Peterborough
country: Canada
facility: GSK Investigational Site
state: Ontario
city: Richmond Hill
country: Canada
facility: GSK Investigational Site
state: Ontario
city: Quebec
country: Canada
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Kang EG, Narayana PK, Pouliquen IJ, Lopez MC, Ferreira-Cornwell MC, Getsy JA. Efficacy and safety of mepolizumab administered subcutaneously for moderate to severe atopic dermatitis. Allergy. 2020 Apr;75(4):950-953. doi: 10.1111/all.14050. Epub 2019 Oct 9. No abstract available.