Asthma
Conditions
Keywords
SB240563, Mepolizumab, self-administration, eosinophilic asthma, autoinjector
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.
Interventions
DRUGMepolizumab
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.
Sponsors
GlaxoSmithKline
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
12 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Successful Self-administration of Their Observed Third Dose at Week 8 - Autoinjector With Standard Label + Pictogram | 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. |
| Percentage of Participants With Successful Self-administration of Their Observed Third Dose at Week 8 - Autoinjector With Standard Label Only | 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
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Successful Self-administration of Their Unobserved Dose at Week 4 - Autoinjector With Standard Label + Pictogram | 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. |
| Percentage of Participants With Successful Self-administration of Their Unobserved Dose at Week 4 - Autoinjector With Standard Label Only | 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. |
Countries
Australia, Canada, Germany, Russia, Sweden, United Kingdom, United States
Participant flow
Recruitment details
Participants with severe eosinophilic asthma, were enrolled at 16 sites in the United States of America, 6 sites in Germany, 5 sites in the United Kingdom, 4 sites in Canada, 3 sites in Australia, 2 sites in Russia and 2 sites in Sweden. The study duration lasted from 04 May 2017 to 30 November 2017.
Pre-assignment details
Of the total 181 participants screened, 22 were screen failures and 159 were enrolled in this open-label, single arm, repeat dose study of mepolizumab and attempted to self-administer at least one dose of study treatment.
Participants by arm
| Arm | Count |
|---|---|
| Mepolizumab Liquid Autoinjector Participants (or their caregivers) self-administered, 100 milligram (mg) mepolizumab liquid drug product subcutaneously every 4 weeks (3 doses) as a single injection using autoinjector, in the thigh, abdomen or upper arm (caregiver only) for 12 weeks. | 159 |
| Total | 159 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 1 |
| Overall Study | Physician Decision | 1 |
Baseline characteristics
| Characteristic | Mepolizumab Liquid Autoinjector |
|---|---|
| Age, Continuous | 49.3 Years STANDARD_DEVIATION 16.18 |
| Race/Ethnicity, Customized African American/African Heritage | 25 Participants |
| Race/Ethnicity, Customized Asian - Central/South Asian Heritage | 2 Participants |
| Race/Ethnicity, Customized Asian - East Asian Heritage | 1 Participants |
| Race/Ethnicity, Customized Asian - South East Asian Heritage | 3 Participants |
| Race/Ethnicity, Customized Other | 1 Participants |
| Race/Ethnicity, Customized White - Arabic/North African Heritage | 1 Participants |
| Race/Ethnicity, Customized White - White/Caucasian/European Heritage | 126 Participants |
| Sex: Female, Male Female | 98 Participants |
| Sex: Female, Male Male | 61 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 159 |
| other Total, other adverse events | 27 / 159 |
| serious Total, serious adverse events | 4 / 159 |
Outcome results
Primary
Percentage of Participants With Successful Self-administration of Their Observed Third Dose at Week 8 - Autoinjector With Standard Label Only
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.
Time frame: Week 8
Population: All Subjects (Safety) Population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Mepolizumab Liquid Autoinjector | Percentage of Participants With Successful Self-administration of Their Observed Third Dose at Week 8 - Autoinjector With Standard Label Only | 98 Percentage of Participants |
Primary
Percentage of Participants With Successful Self-administration of Their Observed Third Dose at Week 8 - Autoinjector With Standard Label + Pictogram
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.
Time frame: Week 8
Population: All Subjects (Safety) Population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Mepolizumab Liquid Autoinjector | Percentage of Participants With Successful Self-administration of Their Observed Third Dose at Week 8 - Autoinjector With Standard Label + Pictogram | 99 Percentage of participants |
Secondary
Percentage of Participants With Successful Self-administration of Their Unobserved Dose at Week 4 - Autoinjector With Standard Label Only
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.
Time frame: Week 4
Population: All Subjects (Safety) Population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Mepolizumab Liquid Autoinjector | Percentage of Participants With Successful Self-administration of Their Unobserved Dose at Week 4 - Autoinjector With Standard Label Only | 96 Percentage of participants |
Secondary
Percentage of Participants With Successful Self-administration of Their Unobserved Dose at Week 4 - Autoinjector With Standard Label + Pictogram
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.
Time frame: Week 4
Population: All Subjects (Safety) Population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Mepolizumab Liquid Autoinjector | Percentage of Participants With Successful Self-administration of Their Unobserved Dose at Week 4 - Autoinjector With Standard Label + Pictogram | 98 Percentage of participants |