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

NCT03055195 | Terminated Phase 2 Results FDA Drug

• 1 other identifier: 205050
• Study Type: interventional
• Target: 34
• Locations: 2 countries
• Sites: 20

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

Keywords

subcutaneous; safety; mepolizumab; efficacy; atopic dermatitis

Outcome Measures

Primary Outcomes (1)

• 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

  The IGA is a clinical tool for assessing the current state/severity of a participant's atopic dermatitis . It is a static 5-point morphological assessment of overall disease severity determined by the investigator, sub-investigator, or trained healthcare professional with required qualifications on a scale of 0 to 4 where, 0-clear, 1-almost clear, 2-mild, 3-moderate, and 4- severe. Higher score indicates severity of disease. A responder is defined as a participant who had an IGA score of 0 or 1 and a minimum 2-grade improvement from Baseline. Number of participants with IGA score of 0 or 1 and at least a 2- grade improvement at Week 16 was presented.

  Week 16

Secondary Outcomes (23)

• Mean Percentage Change in Eczema Area and Severity Index (EASI) Score From Baseline to Each Study Visit

  Baseline (Day 1) and Weeks 4, 8, 12, 16 and 20

• Number of Participants With an IGA Score of 0 or 1 and at Least a 2-grade Improvement at Each Study Visit

  Weeks 4, 8, 12, 16 and 20

• Number of Participants With On-treatment Adverse Events (AEs), Serious Adverse Events (SAEs) and Non-serious Adverse Events (nSAEs)

  Up to Week 20

• Number of Participants With On-treatment AEs of Special Interest Reported as Local Site Injection Reaction and Systemic Reactions

  Up to Week 20

• Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils and Platelets

  Baseline (Day 1) and Weeks 4, 8, 12, 16 and 20

Study Arms (2)

Mepolizumab

EXPERIMENTAL

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

Drug: Mepolizumab 100 mg

Placebo

PLACEBO COMPARATOR

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

Drug: Placebo matching mepolizumab

Interventions

Mepolizumab 100 mg 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.

Mepolizumab

Placebo matching mepolizumab DRUG

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

Placebo

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (20)

GSK Investigational Site

Fort Smith, Arkansas, 72916, United States

Location

GSK Investigational Site

Fremont, California, 94538, United States

Location

GSK Investigational Site

Santa Ana, California, 92701, United States

Location

GSK Investigational Site

Sandy Springs, Georgia, 30328, United States

Location

GSK Investigational Site

Chicago, Illinois, 60612, United States

Location

GSK Investigational Site

Indianapolis, Indiana, 46256, United States

Location

GSK Investigational Site

New Albany, Indiana, 47150, United States

Location

GSK Investigational Site

Louisville, Kentucky, 40241, United States

Location

GSK Investigational Site

Pittsburgh, Pennsylvania, 15213, United States

Location

GSK Investigational Site

San Antonio, Texas, 78213, United States

Location

GSK Investigational Site

Norfolk, Virginia, 23507, United States

Location

GSK Investigational Site

Surrey, British Columbia, V3R 6A7, Canada

Location

GSK Investigational Site

Vancouver, British Columbia, V5Z 4E8, Canada

Location

GSK Investigational Site

Barrie, Ontario, L4M 7G1, Canada

Location

GSK Investigational Site

Markham, Ontario, L3P1X2, Canada

Location

GSK Investigational Site

Oakville, Ontario, L6J 7W5, Canada

Location

GSK Investigational Site

Ottawa, Ontario, K2G 6E2, Canada

Location

GSK Investigational Site

Peterborough, Ontario, K9J 5K2, Canada

Location

GSK Investigational Site

Richmond Hill, Ontario, L4B 1A5, Canada

Location

GSK Investigational Site

Québec, Quebec, G1V 4X7, Canada

Location

Related Publications (1)

• 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.

  PMID: 31515809 BACKGROUND

MeSH Terms

Conditions

Dermatitis, Atopic

Interventions

mepolizumab

Condition Hierarchy (Ancestors)

Skin Diseases, Genetic; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Dermatitis; Skin Diseases; Skin and Connective Tissue Diseases; Skin Diseases, Eczematous; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

GSKClinicalSupportHD@gsk.com

866-435-7343

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR
• Expanded Access: Yes

Study Record Dates

• First Submitted: February 13, 2017
• First Posted: February 16, 2017
• Study Start: March 21, 2017
• Primary Completion: December 6, 2017
• Study Completion: December 6, 2017
• Last Updated: February 25, 2020
• Results First Posted: December 26, 2018

Record last verified: 2020-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: IPD is available via the Clinical Study Data Request site (click on the link provided below)
• Access Criteria: Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.

Locations

US (11); CA (9)