Clinical trial NCT03099096: Study of Mepolizumab Autoinjector in Asthmatics
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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Asthma
Keywords: SB240563
Mepolizumab
self-administration
eosinophilic asthma
autoinjector
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2017-04-04
Enrollment: 159
Sex: ALL
Minimum age (years): 12
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility 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.

Primary outcomes:
measure: Percentage of Participants With Successful Self-administration of Their Observed Third Dose at Week 8 - Autoinjector With Standard Label + Pictogram
timeFrame: Week 8
measure: Percentage of Participants With Successful Self-administration of Their Observed Third Dose at Week 8 - Autoinjector With Standard Label Only
timeFrame: Week 8
Secondary outcomes:
measure: Percentage of Participants With Successful Self-administration of Their Unobserved Dose at Week 4 - Autoinjector With Standard Label + Pictogram
timeFrame: Week 4
measure: Percentage of Participants With Successful Self-administration of Their Unobserved Dose at Week 4 - Autoinjector With Standard Label Only
timeFrame: Week 4
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: GSK Investigational Site
state: Alabama
city: Scottsdale
country: United States
facility: GSK Investigational Site
state: Arizona
city: Los Angeles
country: United States
facility: GSK Investigational Site
state: California
city: San Diego
country: United States
facility: GSK Investigational Site
state: California
city: Colorado Springs
country: United States
facility: GSK Investigational Site
state: Colorado
city: Aventura
country: United States
facility: GSK Investigational Site
state: Florida
city: Miami
country: United States
facility: GSK Investigational Site
state: Florida
city: Albany
country: United States
facility: GSK Investigational Site
state: Georgia
city: Evansville
country: United States
facility: GSK Investigational Site
state: Indiana
city: Baltimore
country: United States
facility: GSK Investigational Site
state: Maryland
city: Saint Louis
country: United States
facility: GSK Investigational Site
state: Missouri
city: Piscataway
country: United States
facility: GSK Investigational Site
state: New Jersey
city: Rochester
country: United States
facility: GSK Investigational Site
state: New York
city: Cincinnati
country: United States
facility: GSK Investigational Site
state: Ohio
city: Medford
country: United States
facility: GSK Investigational Site
state: Oregon
city: Orangeburg
country: United States
facility: GSK Investigational Site
state: South Carolina
city: Woodville South
country: Australia
facility: GSK Investigational Site
state: South Australia
city: Clayton
country: Australia
facility: GSK Investigational Site
state: Victoria
city: Nedlands
country: Australia
facility: GSK Investigational Site
state: Western Australia
city: Sherwood Park
country: Canada
facility: GSK Investigational Site
state: Alberta
city: Toronto
country: Canada
facility: GSK Investigational Site
state: Ontario
city: Windsor
country: Canada
facility: GSK Investigational Site
state: Ontario
city: St. Charles-Borromee
country: Canada
facility: GSK Investigational Site
state: Quebec
city: Ruedersdorf
country: Germany
facility: GSK Investigational Site
state: Brandenburg
city: Frankfurt
country: Germany
facility: GSK Investigational Site
state: Hessen
city: Leipzig
country: Germany
facility: GSK Investigational Site
state: Sachsen
city: Schleswig
country: Germany
facility: GSK Investigational Site
state: Schleswig-Holstein
city: Berlin
country: Germany
facility: GSK Investigational Site
city: Berlin
country: Germany
facility: GSK Investigational Site
city: Chelyabinsk
country: Russian Federation
facility: GSK Investigational Site
city: Voronezh
country: Russian Federation
facility: GSK Investigational Site
city: Linköping
country: Sweden
facility: GSK Investigational Site
city: Lund
country: Sweden
facility: GSK Investigational Site
city: Leicester
country: United Kingdom
facility: GSK Investigational Site
state: Leicestershire
city: Bradford
country: United Kingdom
facility: GSK Investigational Site
city: Oxford
country: United Kingdom
facility: GSK Investigational Site
city: Plymouth
country: United Kingdom
facility: GSK Investigational Site
city: Southampton
country: United Kingdom
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References:
citation: 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.