Phase 2
N=44
A Study to Evaluate the Safety, Efficacy and Changes in Induced Sputum and Blood Biomarkers Following Daily Repeat Doses of Inhaled GSK2269557 in Chronic Obstructive Pulmonary Disease (COPD) Subjects With Acute Exacerbation
Pulmonary Disease, Chronic Obstructive
Bottom Line
View on ClinicalTrials.gov: NCT02522299 ↗Enrolled (actual)
44
Serious AEs
20.5%
Results posted
Nov 2019
Primary outcome: Primary: Change in Messenger Ribonucleic Acid (mRNA) Transcriptome in Induced Sputum After 12, 28 and 84 Days of Treatment (Selected Probe Sets With Fold Change >1.5 or <-1.5 and p<0.05) in NEMI Treatment Group — 1.78; 1.72; 1.67; 1.57 Fold change
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- GSK2269557 (Drug); Placebo (Drug); DISKUS (Device); ELLIPTA (Device)
- Age
- Adult, Older Adult · 40+ yrs
- Sex
- All
- Sponsor
- GlaxoSmithKline
- Primary completion
- Jun 2018
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Change in Messenger Ribonucleic Acid (mRNA) Transcriptome in Induced Sputum After 12, 28 and 84 Days of Treatment (Selected Probe Sets With Fold Change >1.5 or <-1.5 and p<0.05) in NEMI Treatment Group |
1.78; 1.72; 1.67; 1.57; 1.54; 1.51 | — |
| PRIMARY Change in mRNA Transcriptome in Induced Sputum After 12, 28 and 84 Days of Treatment (Selected Probe Sets With Fold Change >1.5 or <-1.5 and p<0.05) in Placebo Treatment Group |
2.29; 1.81; 1.79; 1.61; 1.51; 1.51 | — |
| PRIMARY Change in Messenger Ribonucleic Acid (mRNA) Transcriptome in Induced Sputum After 12, 28 and 84 Days of Treatment (Selected Probe Sets With Fold Change >1.5 or <-1.5 and p<0.05) in All NEMI/All Placebo Comparison Treatment Group |
-1.74; -1.89; -1.60; -1.62; -1.55; 2.75 | — |
| SECONDARY Change From Baseline in Specific Imaging Airway Volume (siVaw) at Functional Residual Capacity (FRC) and Total Lung Capacity (TLC) for Individual Lobes |
1.020; 1.038; 1.027; 1.030; 0.970; 0.993 | — |
| SECONDARY Change From Baseline (Day 12) in siVaw at FRC and TLC for Individual Lobes at Day 28 |
0.998; 0.988; 0.987; 1.014; 1.003; 0.930 | — |
| SECONDARY Change From Baseline in siVaw at FRC and TLC for Individual Regions |
0.996; 1.024; 1.011; 1.029; 1.003; 1.039 | — |
| SECONDARY Change From Baseline (Day 12) in siVaw at FRC and TLC for Individual Regions at Day 28 |
0.996; 0.986; 0.948; 1.025; 0.997; 1.014 | — |
| SECONDARY Change From Baseline in Imaging Airway Volume (iVaw) at FRC and TLC for Individual Lobes |
1.007; 1.044; 1.016; 1.037; 0.965; 0.987 | — |
| SECONDARY Change From Baseline (Day 12) in iVaw at FRC and TLC for Individual Lobes at Day 28 |
0.995; 0.977; 0.973; 1.016; 0.958; 0.943 | — |
| SECONDARY Change From Baseline in iVaw at FRC and TLC for Individual Regions |
0.987; 1.021; 0.999; 1.039; 1.009; 1.017 | — |
| SECONDARY Change From Baseline (Day 12) in iVaw at FRC and TLC for Individual Regions at Day 28 |
0.988; 0.985; 0.934; 1.010; 0.985; 1.008 | — |
| SECONDARY Change From Baseline in Imaging Airway Resistance (iRaw) at FRC and TLC for Individual Lobes |
1.129; 0.876; 1.213; 0.884; 1.058; 0.951 | — |
| SECONDARY Change From Baseline (Day 12) in iRaw at FRC and TLC for Individual Lobes at Day 28 |
1.082; 1.152; 1.266; 1.008; 1.149; 1.477 | — |
| SECONDARY Change From Baseline in iRaw at FRC and TLC for Individual Regions |
0.827; 0.831; 1.395; 0.776; 1.112; 1.066 | — |
| SECONDARY Change From Baseline (Day 12) in iRaw at FRC and TLC for Individual Regions at Day 28 |
1.221; 1.266; 1.531; 1.278; 0.989; 0.926 | — |
| SECONDARY Change From Baseline in Specific Imaging Airway Resistance (siRaw) at FRC and TLC for Individual Lobes |
1.117; 0.961; 1.200; 0.923; 1.053; 0.945 | — |
| SECONDARY Change From Baseline (Day 12) in Specific Imaging Airway Resistance (siRaw) at FRC and TLC for Individual Lobes at Day 28 |
1.079; 1.073; 1.249; 1.011; 1.097; 1.354 | — |
| SECONDARY Change From Baseline in Specific Imaging Airway Resistance (siRaw) at FRC and TLC for Individual Regions |
0.820; 0.828; 1.377; 0.784; 1.118; 1.043 | — |
| SECONDARY Change From Baseline (Day 12) in Specific Imaging Airway Resistance (siRaw) at FRC and TLC for Individual Regions at Day 28 |
1.211; 1.265; 1.508; 1.260; 0.977; 0.921 | — |
| SECONDARY Change From Baseline in Lung Lobar Volume (iVlobe) at FRC and TLC for Individual Lobes |
0.989; 0.971; 0.989; 0.999; 0.995; 0.993 | — |
| SECONDARY Change From Baseline in Lung Lobar Volume (iVlobe) at FRC and TLC for Individual Regions |
0.991; 0.997; 0.987; 1.010; 1.008; 0.979 | — |
| SECONDARY Change From Baseline in Trachea Length and Diameter at FRC and TLC |
0.094; 0.972; 0.796; 0.281; 0.225; 0.252 | — |
| SECONDARY Change From Baseline (Average Day 1 to 3) Peak Expiratory Flow (PEF) |
2.5; 4.1; -3.0; 6.3; 7.3; 7.5 | — |
| SECONDARY Mean Number of Occasions of Rescue Usage Per Day |
3.05; 2.77; 2.93; 2.81; 3.19; 2.84 | — |
| SECONDARY Mean Rescue Medication Free Days |
7.5; 7.7; 5.8; 9.0; 3.7; 7.9 | — |
| SECONDARY Change From Baseline in Forced Expiratory Volume in One Second (FEV1) and Forced Vital Capacity (FVC) |
-0.001; 0.084; 0.005; 0.094; -0.014; 0.112 | — |
| SECONDARY Number of Participants With Worst Case Hematology Results Post-Baseline Relative to Baseline |
0; 0; 0; 0; 0; 0 | — |
| SECONDARY Number of Participants With Worst Case Chemistry Results Post-Baseline Relative to Baseline |
0; 0; 1; 0; 0; 0 | — |
| SECONDARY Number of Participants With Worst Case Vital Sign Results Relative to Potential Clinical Importance (PCI) Criteria Post-Baseline Relative to Baseline |
0; 0; 0; 0; 0; 0 | — |
| SECONDARY Number of Participants With Worst Case Post-Baseline Abnormal Electrocardiogram (ECG) Findings |
10; 7; 6; 7; 0; 0 | — |
| SECONDARY Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE) |
11; 11; 5; 5; 2; 3 | — |
| SECONDARY Maximum Plasma Concentration (Cmax) Following Administration of NEMI |
508.4; 1103.4 | — |
| SECONDARY Trough Concentration Following Administration of NEMI |
313.9; NA; 1097.1; 1077.2; 1194.3; 1225.8 | — |
Summary
The purpose of this study is to evaluate specific alterations in immune cell mechanisms related to neutrophil function as detected by PI3Kdelta-dependent changes in messenger ribonucleic acid (mRNA) extracted from induced sputum in patients experiencing an exacerbation of COPD, with or without treatment with GSK2269557. The efficacy of treatment with GSK2269557 will also be measured using functional respiratory imaging (FRI) and spirometry. This is a randomised, double-blind, placebo-controlled, parallel-group study. The study consisted of Screening Phase (up to 3 days prior to Day 1), Treatment Phase (Days 1 to 84) and Follow phase (7 to 14 days after last dose). The total duration of the study is 13-14 weeks including the screening visit. DISKUS TM and ELLIPTA TM are registered trademark of GSK group of companies.
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 is able to produce >100 milligram (mg) of sputum at screening for processing, (ie, total weight of sputum plugs).
- The subject has a post-bronchodilator FEV1/FVC = 45 kilogram (kg) and body mass index (BMI) within the range 16 to 35 kilogram per meter square (kg/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: (1)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; Documented Bilateral Oophorectomy. Postmenopausal defined as 12 months of spontaneous amenorrhea. Females whose menopausal status is in doubt will be required to use, or have been using, one of the highly effective contraception methods as specified below from 30 days prior to the first dose of study medication and until completion of the follow-up visit. 2)Reproductive potential and agrees to follow one of the options listed below in the GlaxoSmithKline (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. GSK Modified List of Highly Effective Methods for Avoiding Pregnancy in FRP. This list does not apply to FRP with same sex partners, when this is their preferred and usual lifestyle or for subjects who are and will continue to be abstinent from penile-vaginal intercourse on a long term and persistent basis. 1) Contraceptive subdermal implant that meets GSK standard criteria including a 2xupper limit of normal (ULN) and bilirubin >1.5xULN (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin 450 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 or long term antibiotics.
- Subject is being treated with long term oxygen therapy (LTOT) (>15 hours/day).
- The subject has been on chronic treatment with anti-Tumour Necrosis Factor (anti-TNF), or any other immunosuppressive therapy (except corticosteroid) 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 (g) of alcohol: a half-pint (~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 immunodeficiency 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 day
Data sourced from ClinicalTrials.gov (NCT02522299). 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.