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

NCT02294734 | Completed Phase 2 Results

• 2 other identifiers: 1166782014-001972-70
• Study Type: interventional
• Target: 126
• Locations: 5 countries
• Sites: 17

Brief 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.

Conditions

Pulmonary Disease, Chronic Obstructive

Keywords

functional respiratory capacity; High-resolution computed tomography; GSK2269557; acute exacerbation of COPD; lung capacity

Outcome Measures

Primary Outcomes (1)

• 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

  siVaw is a measure of the volume in an individual's airway corrected for their lobar volume derived from the high resolution computed tomography (HRCT). It was measured at functional residual volume (FRC) and total lung capacity (TLC). Data was collected at longitudinal time points: Screening, Day 12 \& Day 28 and at each time point for scan trimmed pairs: SCRD12, SCRD28 \& D12D28. At each time point it was measure at 5 lobes (RUL, LUL, RML, RLL \& LLL) and 5 Regions (Upper, Lower, Central, Distal \& Total). For longitudinal time points and SCRD12 \& SCRD28 scan trimmed pairs the baseline is screening, for D12D28 scan trimmed pair the baseline is D12. Change from baseline is the post-Baseline value minus the Baseline value. Only particpants available at the specified time point were analysed (represented by n=X1, X2 in the category title).

  Baseline, Day 12 and Day 28

Secondary Outcomes (23)

• 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

  Baseline, Day 12 and Day 28

• 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

  Baseline, Day 12 and Day 28

• 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

  Baseline, Day 12 and Day 28

• 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

  Baseline, Day 12 and Day 28

• Change From Baseline in Imaging Trachea Length and Diameter After 12 Days of Treatment and After 28 Days of Treatment

  Baseline, Day 12 and Day 28

Study Arms (2)

GSK2269557 repeat dose

EXPERIMENTAL

Participants will receive 2 inhalation of GSK2269557 dry powder once daily via DISKUS™ 'device' (DISKUS is a trademark of the GSK group of companies)

Drug: GSK2269557

Matching placebo repeat dose

PLACEBO COMPARATOR

Participants will receive 2 inhalation matching placebo dry powder once daily via DISKUS 'device'

Drug: Placebo

Interventions

GSK2269557 DRUG

Dry powder for inhalation via DISKUS 'device' with unit dose strength of 500 micrograms (mcg) per actuation with total dose of 1000 mcg daily

GSK2269557 repeat dose

Placebo DRUG

Dry powder for inhalation via DISKUS 'device'

Matching placebo repeat dose

Eligibility Criteria

• Age: 40 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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) \< 0.7 and FEV1 \<= 80 % of predicted (Predictions should be according to the European Community of Coal and Steel \[ECCS\] equations), documented in the last 5 years.
• Disease severity: Acute exacerbation of COPD requiring an escalation in therapy to include corticosteroid and antibiotics. Acute exacerbation to be confirmed by an experienced physician and represent a recent change in at least two major and one minor symptoms, one major and two minor symptoms, or all 3 major symptoms. Major symptoms: subjective increase in dyspnea, increase in sputum volume, and change in sputum colour. Minor symptoms: cough, wheeze and sore throat.
• The subject is a smoker or an ex-smoker with a smoking history of at least 10 pack years (pack years = \[cigarettes per day smoked/20 x number of years smoked\])
• Body weight \>= 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 \<1% rate of failure per year, as stated in the product label.
• Intrauterine device or intrauterine system that meets the SOP effectiveness criteria including a \<1% rate of failure per year, as stated in the product label.
• Oral Contraceptive, either combined or progestogen alone. Injectable progestogen. Contraceptive vaginal ring. Percutaneous contraceptive patches. Male partner sterilization with documentation of azoospermia prior to the female subject's entry into the study, and this male is the sole partner for that subject.
• Male condom combined with a vaginal spermicide (foam, gel, film, cream, or suppository).

You may not qualify if:

• Need for invasive mechanical ventilation (short term (\< 48hour) Non-invasive Ventilation (NIV) or Continuous Positive Airway Pressure \[CPAP\] is acceptable).
• Haemodynamic instability or clinically significant heart failure. Confusion.
• Subjects who have a history or current medical conditions or diseases that are not well controlled and, which as judged by the Investigator, may affect subject safety or influence the outcome of the study. (Note: Patients with adequately treated and well controlled concurrent medical conditions \[e.g. hypertension or non-insulin dependent diabetes mellitus\] are permitted to be entered into the study).
• Subject has a diagnosis of active tuberculosis, lung cancer, clinically overt bronchiectasis, pulmonary fibrosis, asthma or any other respiratory condition that might, in the opinion of the investigator, compromise the safety of the subject or affect the interpretation of the results.
• Alanine aminotransferase \>2x upper limit of normal (ULN) and bilirubin \>1.5xULN (isolated bilirubin \>1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin \<35%).
• Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
• ECG indicative of an acute cardiac event (e.g. Myocardial Infarction) or demonstrating a clinically significant arrhythmia requiring treatment.
• QTcF \> 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.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (17)

GSK Investigational Site

Edegem, 2650, Belgium

Location

GSK Investigational Site

Erpent, 5101, Belgium

Location

GSK Investigational Site

Aalborg, DK-9100, Denmark

Location

GSK Investigational Site

Copenhagen, DK-2400, Denmark

Location

GSK Investigational Site

Hvidovre, 2650, Denmark

Location

GSK Investigational Site

Odense, 5000 Odense C, Denmark

Location

GSK Investigational Site

Almelo, 7609 PP, Netherlands

Location

GSK Investigational Site

Eindhoven, 5623 EJ, Netherlands

Location

GSK Investigational Site

Zutphen, 7207 AE, Netherlands

Location

GSK Investigational Site

Bucharest, 050159, Romania

Location

GSK Investigational Site

Timișoara, 300310, Romania

Location

GSK Investigational Site

Kemerovo, 650002, Russia

Location

GSK Investigational Site

Moscow, 105 077, Russia

Location

GSK Investigational Site

Saint Petersburg, 194291, Russia

Location

GSK Investigational Site

Vladimir, 600023, Russia

Location

GSK Investigational Site

Yaroslavl, 150003, Russia

Location

GSK Investigational Site

Yekaterinburg, 620109, Russia

Location

Related Publications (1)

• Cahn A, Hamblin JN, Robertson J, Begg M, Jarvis E, Wilson R, Dear G, Leemereise C, Cui Y, Mizuma M, Montembault M, Van Holsbeke C, Vos W, De Backer W, De Backer J, Hessel EM. An Inhaled PI3Kdelta Inhibitor Improves Recovery in Acutely Exacerbating COPD Patients: A Randomized Trial. Int J Chron Obstruct Pulmon Dis. 2021 Jun 3;16:1607-1619. doi: 10.2147/COPD.S309129. eCollection 2021.

  PMID: 34113093 BACKGROUND

MeSH Terms

Conditions

Pulmonary Disease, Chronic Obstructive

Interventions

Nemiralisib

Condition Hierarchy (Ancestors)

Lung Diseases, Obstructive; Lung Diseases; Respiratory Tract Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

866-435-7343

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 17, 2014
• First Posted: November 19, 2014
• Study Start: March 31, 2015
• Primary Completion: February 19, 2016
• Study Completion: April 25, 2016
• Last Updated: August 12, 2021
• Results First Posted: March 9, 2017

Record last verified: 2021-08

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: IPD is available via the Clinical Study Data Request site (copy the URL below to your browser)
• Access Criteria: Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.

Locations

DK (4); RU (6); RO (2); NL (3); BE (2)