Efficacy and Safety Study of Mepolizumab in Subjects With Moderate to Severe Atopic Dermatitis

NCT ID: NCT03055195

Last Updated: 2020-02-25

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 34 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-03-21
• Study Completion Date: 2017-12-06

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).

Conditions

Dermatitis, Atopic

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Mepolizumab

Eligible subjects will receive mepolizumab 100 mg subcutaneously every 4 weeks on Day 1, Week 4, Week 8, and Week 12

Group Type: EXPERIMENTAL

Mepolizumab 100 mg

Intervention Type: DRUG

Mepolizumab is available as lyophilized powder in sterile vials for injection. The content is reconstituted with 1.2 milliliter (mL) Sterile Water just prior to use. Subjects will receive 1mL (100 mg/mL) bolus subcutaneous injections.

Placebo

Eligible subjects will receive matching placebo subcutaneously every 4 weeks on Day 1, Week 4, Week 8, and Week 12

Group Type: PLACEBO_COMPARATOR

Placebo matching mepolizumab

Intervention Type: DRUG

Placebo is available as 0.9% sodium chloride solution. Subjects will receive 1mL bolus subcutaneous injections.

Interventions

Mepolizumab 100 mg

Mepolizumab is available as lyophilized powder in sterile vials for injection. The content is reconstituted with 1.2 milliliter (mL) Sterile Water just prior to use. Subjects will receive 1mL (100 mg/mL) bolus subcutaneous injections.

Intervention Type: DRUG

Placebo matching mepolizumab

Placebo is available as 0.9% sodium chloride solution. Subjects will receive 1mL bolus subcutaneous injections.

Intervention Type: DRUG

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

GlaxoSmithKline

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

GSK Clinical Trials

Role: STUDY_DIRECTOR

GlaxoSmithKline

Locations

GSK Investigational Site

Fort Smith, Arkansas, United States

GSK Investigational Site

Fremont, California, United States

GSK Investigational Site

Santa Ana, California, United States

GSK Investigational Site

Sandy Springs, Georgia, United States

GSK Investigational Site

Chicago, Illinois, United States

GSK Investigational Site

Indianapolis, Indiana, United States

GSK Investigational Site

New Albany, Indiana, United States

GSK Investigational Site

Louisville, Kentucky, United States

GSK Investigational Site

Pittsburgh, Pennsylvania, United States

GSK Investigational Site

San Antonio, Texas, United States

GSK Investigational Site

Norfolk, Virginia, United States

GSK Investigational Site

Surrey, British Columbia, Canada

GSK Investigational Site

Vancouver, British Columbia, Canada

GSK Investigational Site

Barrie, Ontario, Canada

GSK Investigational Site

Markham, Ontario, Canada

GSK Investigational Site

Oakville, Ontario, Canada

GSK Investigational Site

Ottawa, Ontario, Canada

GSK Investigational Site

Peterborough, Ontario, Canada

GSK Investigational Site

Richmond Hill, Ontario, Canada

GSK Investigational Site

Québec, Quebec, Canada

Countries

United States; Canada

References

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.

Reference Type: BACKGROUND

PMID: 31515809 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

205050

Identifier Type: -

Identifier Source: org_study_id