Study of Mepolizumab Autoinjector in Asthmatics

• ClinicalTrials.gov Identifier: NCT03099096
• Recruitment Status: Completed
• First Posted: April 4, 2017
• Results First Posted: June 29, 2018
• Last Update Posted: June 29, 2018
• Sponsor: GlaxoSmithKline
• Information provided by (Responsible Party): GlaxoSmithKline

Study Description

Brief Summary:

This study is aimed to assess the correct real-world use of an autoinjector for the repeat self-administration of mepolizumab SC, so to improve subject / physician convenience and to enable repeat dose self injection themselves or via caregivers. This Phase III study will be an open-label, single-arm, repeat-dose, multi-centre study of mepolizumab liquid drug product in autoinjector (100 milligrams [mg]) administered subcutaneously (SC) every 4 weeks (3 doses) in subjects with severe eosinophilic asthma. Subjects will receive 100 mg mepolizumab SC as a single injection that is self-administered in the thigh, abdomen or administered in the upper arm (caregiver only). Each subject will participate in the study for up to 18 weeks including pre-screening visit, a screening visit and a 12-week treatment period which concludes with end of study assessments (Visit 5) 4 weeks after the last dose of mepolizumab. Approximately 158 subjects will be enrolled in the study.

Condition or disease	Intervention/treatment	Phase
Asthma	Drug: Mepolizumab	Phase 3

Expanded Access : An investigational treatment associated with this study is no longer available outside the clinical trial.   More info ...

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 159 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: An Open-label, Single Arm, Repeat Dose, Multi-centre Study to Evaluate the Use of an Autoinjector for the Subcutaneous Administration of Mepolizumab in Subjects With Severe Eosinophilic Asthma (Study 204959)
• Actual Study Start Date: May 4, 2017
• Actual Primary Completion Date: November 30, 2017
• Actual Study Completion Date: November 30, 2017

Arms and Interventions

Arm

Intervention/treatment

Experimental: Mepolizumab SC 100 mg/milliliter (mL) in autoinjector; Three doses of mepolizumab liquid drug product in autoinjector will be self-administered by the subject/caregiver at 4-weekly intervals; 2 doses will be administered under observation in the clinic (at Week 0 and 8). One dose will be administered outside the clinic and without observation (within 24 hours after attending the clinic at Week 4).

Drug: Mepolizumab; It is a clear to opalescent, colorless to pale yellow sterile solution for SC injection, supplied in a single-use, prefilled syringe containing 100 mg/mL mepolizumab with sodium phosphate, citric acid, sucrose EDTA and polysorbate 80 within an autoinjector.

Outcome Measures

Primary Outcome Measures :

1. Percentage of Participants With Successful Self-administration of Their Observed Third Dose at Week 8 - Autoinjector With Standard Label + Pictogram [ Time Frame: Week 8 ]
   Due to differences in the labelling requirements among regulatory authorities around the world, two different labelling approaches were included in this global study: labelling that includes a pictogram plus standard labelling elements, or a standard labelling without the pictogram. Participants (and/or their caregiver) attended three on treatment visits at Week 0, 4, 8, and End of Study Visit. Training on the study treatment, device handling and administration technique was provided by the investigator or qualified site staff at Week 0 and then first dose was self-administered under observation of investigator/site staff in clinic. Second dose self-administered unobserved, at home (Week 4) and third dose was self-administered under the observation of investigator/site staff in clinic (Week 8). All Subjects (Safety) Population included all enrolled participants attempting at least one self-administration of mepolizumab. Only participants with data available at Week 8 were analyzed.
2. Percentage of Participants With Successful Self-administration of Their Observed Third Dose at Week 8 - Autoinjector With Standard Label Only [ Time Frame: Week 8 ]
   Due to differences in the labeling requirements among regulatory authorities around the world, two different labeling approaches were included in this global study: labeling that includes a pictogram plus standard labeling elements, or a standard labeling without the pictogram. Participants (and/or their caregiver) attended three on treatment visits at Week 0, Week 4, Week 8, and the End of Study Visit. Training on the study treatment, device handling and administration techniques was provided by the investigator or qualified site staff at Week 0 and then first dose was self-administered under observation of investigator/site staff in clinic. Second dose self-administered unobserved, at home (Week 4) and third dose was self-administered under the observation of investigator/site staff in clinic (Week 8). Only participants with data available at Week 8 were analyzed.

Secondary Outcome Measures :

1. Percentage of Participants With Successful Self-administration of Their Unobserved Dose at Week 4 - Autoinjector With Standard Label + Pictogram [ Time Frame: Week 4 ]
   Due to differences in the labeling requirements among regulatory authorities around the world, two different labeling approaches were included in this global study: labeling that includes a pictogram plus standard labeling elements, or a standard labeling without the pictogram. Data for participants (and/or their caregiver) self-administering the second dose unobserved, at home (Week 4) using Autoinjector with Standard Label + Pictogram has been presented. Only participants with data available at Week 4 were analyzed.
2. Percentage of Participants With Successful Self-administration of Their Unobserved Dose at Week 4 - Autoinjector With Standard Label Only [ Time Frame: Week 4 ]
   Due to differences in the labeling requirements among regulatory authorities around the world, two different labeling approaches were included in this global study: labeling that includes a pictogram plus standard labeling elements, or a standard labeling without the pictogram. Data for participants (and/or their caregiver) self-administering the second dose unobserved, at home (Week 4) using Autoinjector with Standard Label has been presented. Only participants with data available at Week 4 were analyzed.

Eligibility Criteria

• Ages Eligible for Study: 12 Years and older (Child, Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Age: At least 12 years of age inclusive, at the time of signing the informed consent. For those countries where local regulations permit enrolment of adults only, subject recruitment will be restricted to those who are >=18 years of age.
• Asthma: A physician diagnosis of asthma for >=2 years that meets the National Heart, Lung and Blood Institute guidelines or Global Initiative for Asthma guidelines.

• Mepolizumab treatment:

  a. Not receiving mepolizumab treatment at Visit 1. These subjects must also meet following inclusion criteria related to eosinophilic asthma, inhaled corticosteroid, controller medication and exacerbation history):

• Eosinophilic asthma: A high likelihood of eosinophilic asthma as per the required 'Continuation to Treatment'-criterion,
• Inhaled corticosteroid: A well-documented requirement for regular treatment with high dose inhaled corticosteroid (ICS) in the 12 months prior to Visit 1 with or without maintenance oral corticosteroids (OCS), for subjects >=18 years old, ICS dose must be >=880 micrograms (mcg)/day fluticasone propionate (FP) (ex-actuator) or equivalent daily, For ICS/long-acting-beta-2-agonist (LABA) combination preparations, the highest approved maintenance dose in the local country will meet this ICS criterion, for subjects >=12 to <=17 years old, ICS dose must be >=440 mcg/day FP (ex-actuator) or equivalent daily, for ICS/LABA combination preparations, the mid-strength approved maintenance dose in the local country will meet this ICS criterion. (Subjects will be permitted to be enrolled without continuous high dose ICS providing the subject was receiving continuous ICS and the Investigator attest that the subject should have been treated with high dose ICS to mitigate the risk of exacerbations, or the subject has financial or tolerance issues that prevent the use of high-dose ICS. Such subjects should be discussed with GSK Medical Monitor prior to enrolment)
• Controller medication: Current treatment with an additional controller medication, besides ICS, for at least 3 months or a documented failure in the past 12 months of an additional controller medication (e.g., LABA, leukotriene receptor antagonist [LTRA], or theophylline) for at least 3 successive months.
• Exacerbation history: Previously confirmed history of one or more exacerbations requiring treatment with systemic corticosteroid (CS) [intramuscular (IM), intravenous, or oral] in the 12 months prior to Visit 1, despite the use of high-dose ICS. For subjects receiving maintenance CS, the CS treatment for an exacerbation must have been a two-fold dose increase or greater.

or, b. Receiving 100 mg SC mepolizumab administered for the treatment of severe eosinophilic asthma every 4 weeks for at least 12 weeks prior to Visit 1.

• Body weight: A minimum body weight >=40 kilograms (kg) at Visit 1
• Gender: 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), planning to become pregnant during the time of study participation (and up to 16 weeks after the last dose), not lactating, and at least one of the following conditions applies: Non-reproductive potential defined as: pre-menopausal females with documented tubal ligation or documented hysteroscopic tubal occlusion procedure with follow-up confirmation of bilateral tubal occlusion or hysterectomy or documented bilateral oophorectomy, postmenopausal female, reproductive potential and agrees to follow highly effective methods for avoiding pregnancy in females of reproductive potential from 30 days prior to the first dose of study medication and until 16 weeks after the last dose of study medication and completion of the end of study/early withdrawal visit. The investigator is responsible for ensuring that subjects understand how to properly use these methods of contraception.
• Informed consent: Capable of giving signed informed consent.

Exclusion Criteria:

• Concurrent respiratory disease: Presence of a known pre-existing, clinically important lung condition other than asthma. This includes current infection, bronchiectasis, pulmonary fibrosis, bronchopulmonary aspergillosis, or diagnoses of emphysema or chronic bronchitis (chronic obstructive pulmonary disease other than asthma) or a history of lung cancer.
• Eosinophilic diseases: Subjects with other conditions that could lead to elevated eosinophils such as hypereosinophilic syndromes, including churg-strauss syndrome, or eosinophilic esophagitis. Subjects with a known, pre-existing parasitic infestation within 6 months prior to Visit 1 will also be excluded.
• Malignancy: A current malignancy or previous history of cancer in remission for less than 12 months prior to screening. Subjects that had localized carcinoma of the skin which was resected for cure will not be excluded.
• Immunodeficiency: A known immunodeficiency (e.g. human immunodeficiency virus [HIV]), other than that explained by the use of corticosteroids taken as therapy for asthma.
• Other concurrent medical conditions: Subjects who have known, pre-existing, clinically significant cardiovascular, endocrine, autoimmune, metabolic, neurological, renal, gastrointestinal, hepatic, haematological or any other system abnormalities that are uncontrolled with standard treatment.
• Liver disease: Known, pre-existing, unstable liver disease (as defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminaemia, esophageal or gastric varices or persistent jaundice), cirrhosis, and known biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
• ECG assessment: QT interval corrected for heart rate by either Fridericia's or Bazett's formula (QTc[F] or QTc[B]) >=450 milliseconds (msec) or QTc(F) or QTc(B) >=480 msec for subjects with bundle branch block at Visit 1.
• Xolair: Subjects who have received omalizumab within 130 days of Visit 1.
• Other monoclonal antibodies not including mepolizumab: Subjects who have received any monoclonal antibody to treat inflammatory disease within 5 half-lives of Visit 1.
• Investigational medications: Subjects who have received treatment with an investigational drug, other than mepolizumab within the past 30 days or five terminal phase half-lives of the drug whichever is longer, prior to visit 1 (this also includes investigational formulations of marketed products) or experimental anti-inflammatory drugs (non biologicals) in the past 3 months.
• Chemotherapy: Subjects who have received chemotherapy within 12 months prior to Visit 1.
• Alcohol/substance abuse: A history (or suspected history) of alcohol misuse or substance abuse within 2 years prior to Visit 1.
• Hypersensitivity: Subjects with hypersensitivity to mepolizumab or to any of the excipients (sodium phosphate, citric acid, sucrose, ethylenediaminetetraacetic acid [EDTA], polysorbate 80).
• Adherence: Subjects who have known evidence of lack of adherence to controller medications and/or ability to follow physician's recommendations.

Contacts and Locations

Locations

United States, Alabama

GSK Investigational Site

Birmingham, Alabama, United States, 35243

United States, Arizona

GSK Investigational Site

Scottsdale, Arizona, United States, 85251

United States, California

GSK Investigational Site

Los Angeles, California, United States, 90025

GSK Investigational Site

San Diego, California, United States, 92123

United States, Colorado

GSK Investigational Site

Colorado Springs, Colorado, United States, 80907

United States, Connecticut

GSK Investigational Site

Waterbury, Connecticut, United States, 06708

United States, Florida

GSK Investigational Site

Aventura, Florida, United States, 33180

GSK Investigational Site

Miami, Florida, United States, 33173

United States, Georgia

GSK Investigational Site

Albany, Georgia, United States, 31707

United States, Indiana

GSK Investigational Site

Evansville, Indiana, United States, 47713

United States, Maryland

GSK Investigational Site

Baltimore, Maryland, United States, 21236

United States, Missouri

GSK Investigational Site

Saint Louis, Missouri, United States, 63141

United States, New Jersey

GSK Investigational Site

Piscataway, New Jersey, United States, 08854

United States, New York

GSK Investigational Site

Rochester, New York, United States, 14642

United States, Ohio

GSK Investigational Site

Cincinnati, Ohio, United States, 45231

United States, Oregon

GSK Investigational Site

Medford, Oregon, United States, 97504

United States, South Carolina

GSK Investigational Site

Orangeburg, South Carolina, United States, 29118

Australia, South Australia

GSK Investigational Site

Woodville South, South Australia, Australia, 5011

Australia, Victoria

GSK Investigational Site

Clayton, Victoria, Australia, 3169

Australia, Western Australia

GSK Investigational Site

Nedlands, Western Australia, Australia, 6009

Canada, Alberta

GSK Investigational Site

Sherwood Park, Alberta, Canada, T8H 0N2

Canada, Ontario

GSK Investigational Site

Toronto, Ontario, Canada, M5T 3A9

GSK Investigational Site

Windsor, Ontario, Canada, N8X 2G1

Canada, Quebec

GSK Investigational Site

St. Charles-Borromee, Quebec, Canada, J6E 2B4

Germany

GSK Investigational Site

Ruedersdorf, Brandenburg, Germany, 15562

GSK Investigational Site

Frankfurt, Hessen, Germany, 60389

GSK Investigational Site

Leipzig, Sachsen, Germany, 04357

GSK Investigational Site

Schleswig, Schleswig-Holstein, Germany, 24837

GSK Investigational Site

Berlin, Germany, 10717

GSK Investigational Site

Berlin, Germany, 12203

Russian Federation

GSK Investigational Site

Chelyabinsk, Russian Federation, 454021

GSK Investigational Site

Voronezh, Russian Federation, 394066

Sweden

GSK Investigational Site

Linköping, Sweden, SE-581 85

GSK Investigational Site

Lund, Sweden, SE-221 85

United Kingdom

GSK Investigational Site

Leicester, Leicestershire, United Kingdom, LE3 9QP

GSK Investigational Site

Bradford, United Kingdom, BD96RJ

GSK Investigational Site

Oxford, United Kingdom, OX37LE

GSK Investigational Site

Plymouth, United Kingdom, PL6 8DH

GSK Investigational Site

Southampton, United Kingdom, SO16 6YD

Sponsors and Collaborators

GlaxoSmithKline

Investigators

• Study Director: GSK Clinical Trials; GlaxoSmithKline

  Study Documents (Full-Text)

Documents provided by GlaxoSmithKline:

Study Protocol  [PDF] February 15, 2017

Statistical Analysis Plan  [PDF] November 30, 2017

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Bernstein D, Pavord ID, Chapman KR, Follows R, Bentley JH, Pouliquen I, Bradford E. Usability of mepolizumab single-use prefilled autoinjector for patient self-administration. J Asthma. 2020 Sep;57(9):987-998. doi: 10.1080/02770903.2019.1630641. Epub 2019 Jun 28.

• Responsible Party: GlaxoSmithKline
• ClinicalTrials.gov Identifier: NCT03099096
• Other Study ID Numbers: 204959
• First Posted: April 4, 2017
• Results First Posted: June 29, 2018
• Last Update Posted: June 29, 2018
• Last Verified: May 2018

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by GlaxoSmithKline:

SB240563; Mepolizumab; self-administration; eosinophilic asthma; autoinjector

Additional relevant MeSH terms:

Asthma; Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases