The primary endpoint was the moderate/severe acute exacerbations of COPD (AECOPD) rate (week 56 post-randomisation)
July 25, 2022
The primary endpoint was the moderate/severe acute exacerbations of COPD (AECOPD) rate (week 56 post-randomisation). therapy with 2 exacerbations in the past year were randomised 1:1 to receive placebo or MEDI8968 300?mg (600?mg intravenous loading dose) subcutaneously every 4?weeks, for 52?weeks. The primary endpoint was the moderate/severe acute Mogroside II A2 exacerbations of Mogroside II A2 COPD (AECOPD) rate (week 56 post-randomisation). Secondary endpoints were severe AECOPD rate and St Georges Respiratory Questionnaire-COPD (SGRQ-C) score (week 56 Rabbit Polyclonal to CDKL2 post-randomisation). Results Of subjects randomised to placebo (analysis of subject subgroups (by baseline neutrophil count or tertiles of circulating neutrophil counts) did not alter the study outcome. The incidence of treatment-emergent adverse events (TEAEs) with placebo and MEDI8968 treatment was comparable. The most common TEAE was worsening of COPD. Conclusions In this phase II study, MEDI8968 did not produce statistically significant improvements in AECOPD rate, lung function or quality of life. Trial registration ClinicalTrials.gov, “type”:”clinical-trial”,”attrs”:”text”:”NCT01448850″,”term_id”:”NCT01448850″NCT01448850, date of registration: 06 October 2011. Electronic supplementary material The online version of this article (doi:10.1186/s12931-017-0633-7) contains supplementary material, which is available to authorized users. analyses, blood neutrophil counts. Methods Subjects We enrolled subjects aged 45C75?years with symptomatic, moderate-to-very severe COPD (Global Initiative for Chronic Obstructive Lung Disease [Platinum] stage IICIV ), receiving standard maintenance therapy and who also had 2 AECOPD that required oral corticosteroids, antibiotics or hospitalisation in the 12? months prior to screening. Full inclusion, exclusion and study-stopping criteria are outlined in the online Additional file 1. Study design This was a phase II, randomised, double-blind, placebo-controlled, multicentre, parallel-group study (CP1103; ClinicalTrials.gov “type”:”clinical-trial”,”attrs”:”text”:”NCT01448850″,”term_id”:”NCT01448850″NCT01448850), conducted at 68 sites in Bulgaria, Czech Republic, Hungary, Latvia, Lithuania, Philippines, Poland, Ukraine, United Kingdom and United States. The study consisted of a 17C23-day run-in period (visits 1C3) and a 52-week treatment period (visits 4C19; weeks 1, 4, 5, 8, 9 and every 4?weeks [Q4W] thereafter until week 53). Subjects returned to the medical center 8?weeks (week 61) and 16?weeks (week 69) after the treatment period, for follow-up visits (visits 20C21). During screening, FEV1 measurements decided the standard maintenance care therapy (budesonide/formoterol or tiotropium or budesonide/formoterol plus tiotropium), which replaced the existing maintenance therapy and was assigned for each subject at the start of run-in (online Additional file 1). Following screening/run-in, subjects were randomised 1:1 to receive placebo or MEDI8968 as a 600?mg intravenous (IV) dose on Mogroside II A2 day 1 (loading dose), followed by 300?mg subcutaneous (SC) (two 150?mg injections) Q4W, for a total of 14 doses. The single 600?mg IV infusion was administered over a minimum of 1?h (for further details on randomisation and blinding, see the online Additional file 1). Assessments The primary endpoint was the annualised rate of moderate/severe AECOPD, including data up to week 56, summarised as a per-person-per-year rate (measured at all visits during treatment and follow-up). An AECOPD was defined as worsening of 2 major symptoms (dyspnoea, sputum volume, sputum purulence) or worsening of one major and one minor symptom (sore throat, chilly, fever without other cause, Mogroside II A2 increased cough or wheeze) for 2 consecutive days . The severity of AECOPD was categorised based on the treatment required: increase in normal therapy, Mogroside II A2 antibiotics/systemic corticosteroids or hospitalisation for moderate, moderate or severe AECOPD, respectively. Additionally, the moderate/severe AECOPD rate was compared between subjects by baseline CRP (0.347?mg/dL cut-off; inclusion criterion for a study of canakinumab in COPD ) and fibrinogen ( median cut-off) concentrations as part of a pre-specified analysis. Secondary endpoints included severe AECOPD rate and change from baseline in SGRQ-C total and symptom domain scores (measured at weeks 1, 5, 13, 25, 37, 53 and 69) [20, 21]. Exploratory endpoints included change from baseline in pre-bronchodilator FEV1 and change from baseline in Exacerbations.