Primary: To evaluate the effect of once daily repeat inhaled doses of GSK2269557 on lung parameters derived from HRCT scans in subjects with acute exacerbation of COPD,compared to placebo. Secondary: Other lung parameters derived from high…
ID
Source
Brief title
Condition
- Respiratory disorders NEC
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
siVaw at FRC and TLC after 12 and 28 days of treatment.
Secondary outcome
Whole body plethysmography parameters (e.g. iVaw, (s)iRaw), trachea length and
diameter, adverse events, PK parameters, FEV1 and PEF, questionnaires, number
of treatment failures and time to next exacerbation (see protocol page 10 for
details).
Background summary
GSK2269557 is a potent and highly selective inhaled Phosphoinositide 3-Kinase
Delta (PI3Kd) inhibitor being developed as an anti-inflammatory and
anti-infective agent for the treatment of inflammatory airways diseases.
PI3Kd is thought to play a role in a number of epithelial responses relevant
for the development of COPD. Therefore a PI3Kd inhibitor may be able to
suppress a number of these processes. A greater proportion of macrophages
appear to be alternatively activated in COPD and their ability to phagocytose
infective pathogens is reduced as a result of this alternative activation.
PI3Kd is one of the mediators involved in determining this alternative
phenotype in macrophages and therefore it is proposed that inhibition of PI3Kd
might rebalance macrophage activation towards a classic phagocytic
phenotype facilitating clearance of bacteria. The neutrophil and T cell are the
two major inflammatory cell types involved in the pathogenesis of COPD and both
are targeted by PI3Kd inhibitors.
Existing data suggests that repeat dosing with GSK2269557 could potentially
reduce the impact of an acute exacerbation, or prevent the onset of a secondary
exacerbation.
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 COPD.
To date GSK2269557 has not been administered to subjects with an acute
exacerbation of COPD, but has been safely administered to healthy volunteers
and a study in stable COPD subjects is currently ongoing.
Study objective
Primary: To evaluate the effect of once daily repeat inhaled doses of
GSK2269557 on lung parameters derived from HRCT scans in subjects with acute
exacerbation of COPD,
compared to placebo.
Secondary: Other lung parameters derived from high resolution (HR) CT-scans,
safety and tolerability, PK, number of treatment failures, time to next
exacerbation.
Study design
Randomised, double-blind (sponsor unblended), placebo-controlled,
parallel-group phase IIA study. Randomisation (1:1) upon diagnosis acute
exacerbation of COPD to inhaled
• GSK2269557 once daily
• Placebo.
on top of standard treatment.
Screening max. 3 days. Treatment period 12 weeks. Follow-up period 1-2 weeks.
Approx. 120 patients.
Intervention
Treatment with GSK2269557 or placebo.
Study burden and risks
Risk: adverse events of study treatment.
Burden: 8 visits in approx. 14 weeks.
Physical examination 6-7 times.
Blood draws 6-7 times (approx. 100 ml in total).
Pregnancy test 3 times.
Whole body plethysmography 3 times.
HRCT-scans 3 times.
ECG 6-7 times.
3 times completion of 1 questionnaire.
Pulmonary function test (FEV1, PEF) daily (at home).
Paper diary for AEs, study medication and concomitant medication.
Optional:
- pharmacogenetic research (6 ml blood once).
- biomarker research (4 times sputum and 2,5 ml blood).
Huis ter Heideweg 62
Zeist 3705 LZ
NL
Huis ter Heideweg 62
Zeist 3705 LZ
NL
Listed location countries
Age
Inclusion criteria
• Between 40 and 80 years of age inclusive.
• Confirmed diagnosis of COPD (GOLD guidelines) for at least 6 months.
• Post-bronchodilator FEV1/FVC < 0.7 and FEV1 <= 80 % of predicted, documented in the last 5 years.
• Acute exacerbation of COPD requiring an escalation in therapy to include corticosteroid and antibiotics. See protocol page 23-24 for details.
• Smoker or an ex-smoker with a smoking history of at least 10 pack years.
• Body weight >=45 kg and BMI within the range 18 - 32 kg/m2 (inclusive).
• Adequate contraception for females of childbearing potential. See protocol page 25-26 for details.
Exclusion criteria
• Severe COPD exacerbation. To avoid recruitment of subjects with a severe COPD exacerbation, the presence of any one of the following severity criteria will render the subject ineligible for inclusion in the study:
- Need for invasive mechanical ventilation (short term (< 48h) NIV or CPAP is acceptable)
- Haemodynamic instability or clinically significant heart failure
- Confusion
- Clinically significant pneumonia, identified by chest X-ray (if available) or on the CT scan performed during screening. See protocol page 28 for more details.
• ECG indicative of an acute cardiac event or demonstrating a clinically significant arrhythmia requiring treatment.
• QTc prolongation. See protocol page 27 for details.
• Chronic treatment with macrolides; long term oxygen therapy (>15 hours/day).
• Chronic treatment with anti-TNF, anti-IL1, or any other immunosuppressive therapy within 60 days prior to dosing.
• Exposure to more than 4 investigational medicinal products within 12 months prior to the first dosing day.
• Pregnancy or breastfeeding
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2014-001972-70-NL |
| Other | gsk-clinicalstudyregister.com; registratienummer 116678 |
| CCMO | NL51467.015.14 |