Phase 2 N=126 Randomized Double-blind Treatment

An Efficacy Study of GSK2269557 Added to Standard Care in Subjects With an Acute Exacerbation of Chronic Obstructive Pulmonary Disease

Pulmonary Disease, Chronic Obstructive

Bottom Line

View on ClinicalTrials.gov: NCT02294734 ↗

Enrolled (actual)

126

Serious AEs

14.3%

Results posted

Mar 2017

Primary outcome: Primary: Change From Baseline in Specific Imaging Airway Volume (siVaw), Measured at FRC and TLC Scan Conditions, Presented in Longitudinal and Scan Trimmed Scan Types, Measured in 5 Lobes and 5 Regions at Screening, Day 12 and Day 28 — 1.033; 1.052; 0.983; 1.075 Milliliter/Liter (mL/L) — p=60.66

Study Design & Population

Study type: Interventional
Phase: Phase 2
Interventions: GSK2269557 (Drug); Placebo (Drug)
Age: Adult, Older Adult · 40+ yrs
Sex: All
Sponsor: GlaxoSmithKline
Primary completion: Feb 2016

Outcome Measures

Outcome	Result	p-value
PRIMARY Change From Baseline in Specific Imaging Airway Volume (siVaw), Measured at FRC and TLC Scan Conditions, Presented in Longitudinal and Scan Trimmed Scan Types, Measured in 5 Lobes and 5 Regions at Screening, Day 12 and Day 28	1.033; 1.052; 0.983; 1.075; 0.975; 1.000	60.66
SECONDARY Change From Baseline in Imaging Airways Volume: iVaw, Measured at FRC and TLC Scan Conditions, Presented in Longitudinal and Scan Trimmed Scan Types, Measured in 5 Lobes and 5 Regions at Screening, Day 12 and Day 28	1.020; 1.058; 0.960; 1.121; 0.951; 0.999	59.55
SECONDARY Change From Baseline in Imaging Airways Resistance ( iRaw) Measured at FRC and TLC Scan Conditions, Presented in Scan Trimmed Scan Types, Measured in 5 Lobes and 5 Regions at Screening, Day 12 and Day 28	0.908; 0.948; 0.849; 0.958; 1.039; 0.898	60.07
SECONDARY Change From Baseline in Imaging Specific Airways Resistance: siRaw Measured at FRC and TLC Scan Conditions, Presented in Scan Trimmed Scan Types, Measured in 5 Lobes and 5 Regions at Screening, Day 12 and Day 28	0.896; 0.908; 0.829; 1.013; 1.035; 0.926	67.19
SECONDARY Change From Baseline in Lung Lobar Volumes Measured at FRC and TLC Scan Conditions, Presented in Longitudinal Scan Types, Measured in 5 Lobes and 5 Regions at Day 12 and Day 28	0.983; 0.995; 0.977; 1.017; 0.974; 0.998	32.51
SECONDARY Change From Baseline in Imaging Trachea Length and Diameter After 12 Days of Treatment and After 28 Days of Treatment	-1.886; 0.517; -1.434; 0.485; -0.247; 0.059	2.89
SECONDARY Change From Baseline in Imaging Trachea Length/Diameter After 12 Days of Treatment and After 28 Days of Treatment	-0.030; 0.000; -0.017; 0.059; 0.024; -0.023	28.51
SECONDARY Number of Participants With Adverse Events (AE)	41; 49	—
SECONDARY Number of Participants With Abnormal Hematology Parameters	4; 1; 1; 1; 1; 1	—
SECONDARY Number of Participants With Abnormal Clinical Chemistry Parameters	0; 1; 0; 0; 1; 0	—
SECONDARY Number of Participants With Abnormal Vital Signs	1; 0; 0; 0; 0; 0	—
SECONDARY Number of Participants With Abnormal 12-lead Electrocardiogram (ECG)	45; 40; 0; 0; 43; 40	—
SECONDARY Day 1 Plasma Concentration up to 24 Hours (Hrs) Post-dose	33.0; 476.6; 553.7; 539.0	—
SECONDARY Trough Concentration After 12 Days, 28 Days, 56 Days and 84 Days of Treatment	1001.8; 1028.8; 1119.8; 948.6	—
SECONDARY Changes From Baseline in Forced Expiratory Volume in One Second (FEV1) Measured Daily	-70.4; -72.2; -83.3; -22.7	0.487
SECONDARY Changes From Baseline in Peak Expiratory Flow (PEF) Measured Daily	-13.12; -4.76; -0.52; -0.85	—
SECONDARY Percent Change From Baseline in Diffusion Capacity (DLco, Kco) After 28 Days and After 84 Days of Treatment	-2.783; -0.687; -2.385; 0.560; -2.745; -0.875	—
SECONDARY Change From Baseline in Total Lung Capacity (TLC) After 28 Days and After 84 Days of Treatment	-0.010; -0.155; -0.149; -0.029	0.151
SECONDARY Change From Baseline in Residual Volume After 28 Days and After 84 Days of Treatment	-0.157; 0.022; -0.113; 0.001	0.817
SECONDARY Change From Baseline in Functional Residual Capacity After 28 Days and After 84 Days of Treatment	0.0010; -0.0919; -0.2219; -0.0505	—
SECONDARY Change From Baseline in Specific Resistance (sRaw) After 28 Days and After 84 Days of Treatment	0.9734; 0.8372; 0.9949; 0.8495	—
SECONDARY Change From Baseline in Specific Conductance (sGaw) After 28 Days and After 84 Days of Treatment	0.875; 1.024; 0.965; 1.075	0.965
SECONDARY Questionnaires CAT and MMRC Scale at Baseline, Day 28 and Day 84	-0.4; -0.7; -0.6; -0.7; -0.6; -0.3	—
SECONDARY Number of Participants With Treatment Failures	17; 13; 9; 7; 4; 3	—

Summary

The purpose of this study is to evaluate the efficacy of GSK2269557 administered in addition to standard of care in adult subjects diagnosed with an acute exacerbation of Chronic Obstructive Pulmonary Disease (COPD). Additionally study will also assess safety, tolerability and pharmacokinetic data. The total duration of the study will be 13-14 weeks including screening, treatment period and a follow up visit. Subjects will receive once daily study treatment administration starting on Day 1. Study is planned to recruit approximately 120 subjects such that approximately 100 subjects complete the study.

Eligibility Criteria

Inclusion Criteria

Between 40 and 80 years of age inclusive, at the time of signing the informed consent
The subject has a confirmed and established diagnosis of COPD, as defined by the global initiative for chronic Obstructive Lung Disease (GOLD) guidelines for at least 6 months prior to entry.
The subject has a post-bronchodilator FEV1/Forced Vital Capacity (FVC) = 45 kilogram (kg) and body mass index (BMI) within the range 18 - 32 kg/metered squared (m^2) (inclusive).
Male
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 applies:

Non-reproductive potential defined as: Pre-menopausal females with one of the following: documented tubal ligation, documented hysteroscopic tubal occlusion procedure with follow-up confirmation of bilateral tubal occlusion, hysterectomy and documented bilateral oophorectomy. 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 (refer to laboratory reference ranges for confirmatory levels). 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 below in the GSK Modified List of Highly Effective Methods for Avoiding Pregnancy in Females of Reproductive Potential (FRP) requirements from 30 days prior to the first dose of study medication and until completion of the follow-up visit.

GlaxoSmithKline (GSK) Modified List of Highly Effective Methods for Avoiding Pregnancy in Females of Reproductive Potential (FRP):

Contraceptive subdermal implant that meets the standard operating procedure (SOP) effectiveness criteria including a 2x upper limit of normal (ULN) and bilirubin >1.5xULN (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin 450 millisecond (msec) or QTcF > 480 msec in subjects with Bundle Branch Block, based on single QTcF value.

Subjects who have undergone lung volume reduction surgery.
Subject is currently on chronic treatment with macrolides; long term oxygen therapy (> 15 hours/day).
The subject has been on chronic treatment with anti-Tumour Necrosis Factor (anti-TNF), anti-Interleukin-1 (anti-IL1), or any other immunosuppressive therapy within 60 days prior to dosing.
History of regular alcohol consumption within 6 months of the study defined as an average weekly intake of >28 units for males or >21 units for females. One unit is equivalent to 8 gram of alcohol: a half-pint ( equivalent to 240 milliliter [mL]) of beer, 1 glass (125 mL) of wine or 1 (25 mL) measure of spirits.
History of sensitivity to any of the study medications, or components thereof (such as lactose) or a history of drug or other allergy that, in the opinion of the investigator or Medical Monitor, contraindicates their participation.
A known (historical) positive test for human immune virus (HIV) antibody.
Presence of hepatitis B surface antigen (HBsAg), positive hepatitis C antibody test result at screening or within 3 months prior to first dose of study treatment. NOTE: Because of the short window for screening, treatment with GSK2269557 may start before receiving the result of the hepatitis tests. If subsequently the test is found to be positive, the subject may be withdrawn, as judged by the Principal Investigator in consultation with the Medical Monitor.
Where participation in the study would result in donation of blood or blood products in excess of 500 mL within 56 days.
The subject has participated in a clinical

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Data sourced from ClinicalTrials.gov (NCT02294734). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.