Study of Mepolizumab Autoinjector in Asthmatics

• Sponsor: GlaxoSmithKline (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03099096
• Collaborator: (none)
• Enrollment: 159
• Locations: 39
• Arm: 1
• Actual Duration (Months): 6.9
• Patients Per Site: 4.1
• Patients Per Site Per Month: 0.6

Study Details

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

Study Design

• Study Type: Interventional
• 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: Nov 30, 2017
• Actual Study Completion Date: Nov 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 [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 [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 [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 [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

Criteria

• Ages Eligible for Study: 12 Years and Older
• Sexes Eligible for Study: All
• Accepts 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:

1. 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

• 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

	Site	City	State	Country	Postal Code
1	GSK Investigational Site	Birmingham	Alabama	United States	35243
2	GSK Investigational Site	Scottsdale	Arizona	United States	85251
3	GSK Investigational Site	Los Angeles	California	United States	90025
4	GSK Investigational Site	San Diego	California	United States	92123
5	GSK Investigational Site	Colorado Springs	Colorado	United States	80907
6	GSK Investigational Site	Waterbury	Connecticut	United States	06708
7	GSK Investigational Site	Aventura	Florida	United States	33180
8	GSK Investigational Site	Miami	Florida	United States	33173
9	GSK Investigational Site	Albany	Georgia	United States	31707
10	GSK Investigational Site	Evansville	Indiana	United States	47713
11	GSK Investigational Site	Baltimore	Maryland	United States	21236
12	GSK Investigational Site	Saint Louis	Missouri	United States	63141
13	GSK Investigational Site	Piscataway	New Jersey	United States	08854
14	GSK Investigational Site	Rochester	New York	United States	14642
15	GSK Investigational Site	Cincinnati	Ohio	United States	45231
16	GSK Investigational Site	Medford	Oregon	United States	97504
17	GSK Investigational Site	Orangeburg	South Carolina	United States	29118
18	GSK Investigational Site	Woodville South	South Australia	Australia	5011
19	GSK Investigational Site	Clayton	Victoria	Australia	3169
20	GSK Investigational Site	Nedlands	Western Australia	Australia	6009
21	GSK Investigational Site	Sherwood Park	Alberta	Canada	T8H 0N2
22	GSK Investigational Site	Toronto	Ontario	Canada	M5T 3A9
23	GSK Investigational Site	Windsor	Ontario	Canada	N8X 2G1
24	GSK Investigational Site	St. Charles-Borromee	Quebec	Canada	J6E 2B4
25	GSK Investigational Site	Ruedersdorf	Brandenburg	Germany	15562
26	GSK Investigational Site	Frankfurt	Hessen	Germany	60389
27	GSK Investigational Site	Leipzig	Sachsen	Germany	04357
28	GSK Investigational Site	Schleswig	Schleswig-Holstein	Germany	24837
29	GSK Investigational Site	Berlin		Germany	10717
30	GSK Investigational Site	Berlin		Germany	12203
31	GSK Investigational Site	Chelyabinsk		Russian Federation	454021
32	GSK Investigational Site	Voronezh		Russian Federation	394066
33	GSK Investigational Site	Linköping		Sweden	SE-581 85
34	GSK Investigational Site	Lund		Sweden	SE-221 85
35	GSK Investigational Site	Leicester	Leicestershire	United Kingdom	LE3 9QP
36	GSK Investigational Site	Bradford		United Kingdom	BD96RJ
37	GSK Investigational Site	Oxford		United Kingdom	OX37LE
38	GSK Investigational Site	Plymouth		United Kingdom	PL6 8DH
39	GSK Investigational Site	Southampton		United Kingdom	SO16 6YD

Sponsors and Collaborators

• GlaxoSmithKline

Investigators

• Study Director: GSK Clinical Trials, GlaxoSmithKline

Study Documents (Full-Text)

• Study Protocol - Feb 15, 2017
• Statistical Analysis Plan - Nov 30, 2017

More Information

Publications

None provided.

• Responsible Party: GlaxoSmithKline
• ClinicalTrials.gov Identifier: NCT03099096
• Other Study ID Numbers: 204959
• First Posted: Apr 4, 2017
• Last Update Posted: Jun 29, 2018
• Last Verified: May 1, 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

Study Results

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 Detail	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.

Arm/Group Title	Mepolizumab Liquid Autoinjector
Arm/Group Description	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.
Period Title: Overall Study
STARTED	159
COMPLETED	157
NOT COMPLETED	2

Baseline Characteristics

Arm/Group Title	Mepolizumab Liquid Autoinjector
Arm/Group Description	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.
Overall Participants	159
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	49.3 (16.18)
Sex: Female, Male (Count of Participants)
Female	98 61.6%
Male	61 38.4%
Race/Ethnicity, Customized (Count of Participants)
African American/African Heritage	25 15.7%
Asian - Central/South Asian Heritage	2 1.3%
Asian - East Asian Heritage	1 0.6%
Asian - South East Asian Heritage	3 1.9%
White - Arabic/North African Heritage	1 0.6%
White - White/Caucasian/European Heritage	126 79.2%
Other	1 0.6%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants With Successful Self-administration of Their Observed Third Dose at Week 8 - Autoinjector With Standard Label + Pictogram
Description	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

Outcome Measure Data

Analysis Population Description

All Subjects (Safety) Population

Arm/Group Title	Mepolizumab Liquid Autoinjector
Arm/Group Description	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.
Measure Participants	103
Number [Percentage of participants]	99 62.3%

2. Primary Outcome

Title	Percentage of Participants With Successful Self-administration of Their Observed Third Dose at Week 8 - Autoinjector With Standard Label Only
Description	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

Outcome Measure Data

Analysis Population Description

All Subjects (Safety) Population

Arm/Group Title	Mepolizumab Liquid Autoinjector
Arm/Group Description	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.
Measure Participants	54
Number [Percentage of Participants]	98 61.6%

3. Secondary Outcome

Title	Percentage of Participants With Successful Self-administration of Their Unobserved Dose at Week 4 - Autoinjector With Standard Label + Pictogram
Description	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

Outcome Measure Data

Analysis Population Description

All Subjects (Safety) Population

Arm/Group Title	Mepolizumab Liquid Autoinjector
Arm/Group Description	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.
Measure Participants	103
Number [Percentage of participants]	98 61.6%

4. Secondary Outcome

Title	Percentage of Participants With Successful Self-administration of Their Unobserved Dose at Week 4 - Autoinjector With Standard Label Only
Description	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

Outcome Measure Data

Analysis Population Description

All Subjects (Safety) Population

Arm/Group Title	Mepolizumab Liquid Autoinjector
Arm/Group Description	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.
Measure Participants	54
Number [Percentage of participants]	96 60.4%

Adverse Events

Time Frame	On-treatment serious adverse events (SAEs) and non-serious AEs were collected from start of Study Treatment (Week 0) until the End of Study/Early Withdrawal Visit (Week 12)
Adverse Event Reporting Description	On-treatment SAEs and non-serious AEs are reported for All Subjects (Safety) Population
Arm/Group Title	Mepolizumab Liquid Autoinjector
Arm/Group Description	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.
All Cause Mortality
	Mepolizumab Liquid Autoinjector
	Affected / at Risk (%)	# Events
Total	0/159 (0%)
Serious Adverse Events
	Mepolizumab Liquid Autoinjector
	Affected / at Risk (%)	# Events
Total	4/159 (2.5%)
General disorders
Chest discomfort	1/159 (0.6%)	1
Injury, poisoning and procedural complications
Cervical vertebral fracture	1/159 (0.6%)	1
Facial bones fracture	1/159 (0.6%)	1
Rib fracture	1/159 (0.6%)	1
Road traffic accident	1/159 (0.6%)	1
Skull fractured base	1/159 (0.6%)	1
Respiratory, thoracic and mediastinal disorders
Alveolitis allergic	1/159 (0.6%)	1
Asthma	1/159 (0.6%)	1
Pneumothorax	1/159 (0.6%)	1
Other (Not Including Serious) Adverse Events
	Mepolizumab Liquid Autoinjector
	Affected / at Risk (%)	# Events
Total	27/159 (17%)
Infections and infestations
Nasopharyngitis	9/159 (5.7%)	11
Upper respiratory tract infection	6/159 (3.8%)	6
Lower respiratory tract infection	5/159 (3.1%)	5
Urinary tract infection	5/159 (3.1%)	5
Nervous system disorders
Headache	8/159 (5%)	11

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.