Clinical Trials

Date: 2017-09-20

Type of information: Results

phase: 3

Announcement: results

Company: GSK (UK) Theravance, now Innoviva (USA - CA)

Product: Trelegy Ellipta® (combination of fluticasone furoate, umeclidinium and vilanterol)

Action mechanism:

• corticosteroid/long-acting beta2-agonist (LABA)long-acting muscarinic antagonist (LAMA). This treatment combines an inhaled corticosteroid (fluticasone furoate); a long-acting muscarinic antagonist (umeclidinium); and a long-acting beta2-adrenergic agonist (vilanterol), all delivered in GSK's Ellipta inhaler.

Disease: chronic obstructive pulmonary disease (COPD)

Therapeutic area: Respiratory diseases

Country:

Trial details:

• IMPACT (InforMing the PAthway of COPD Treatment) is a double-blind, three-arm, parallel group study enrolling a total of 10,000 patients across 38 countries. Eligible patients have been  randomised to receive either fluticasone furoate, umeclidinium and vilanterol (FF/UMEC/VI) 100/62.5/25mcg, fluticasone furoate and vilanterol  (FF/VI) 100/25mcg or umeclidinium and vilanterol (UMEC/VI) 62.5/25mcg once-daily for a period of 52 weeks. The co-primary endpoints of the study are:
• - the annual rate of moderate and severe exacerbations comparing FF/UMEC/VI with FF/VI;
• - and the annual rate of moderate and severe exacerbations comparing FF/UMEC/VI with UMEC/VI.
• Key secondary endpoints include baseline changes in lung function (trough FEV1) comparing FF/UMEC/VI and FF/VI; time to first moderate or severe exacerbation in all three arms of the study; and the annual rate of severe exacerbations in all three arms of the study.

Latest news:

• • On September 20, 2017, GSK and Innoviva reported headline results from the landmark phase III IMPACT study of Trelegy Ellipta®. The study, which involved 10,355 patients, met its primary endpoint demonstrating statistically significant reductions in the annual rate of on-treatment moderate/severe exacerbations for FF/UMEC/VI (100/62.5/25mcg) when compared with two, once-daily dual COPD therapies from GSK’s existing portfolio.
• The study showed a:
• 15% reduction for FF/UMEC/VI compared with Relvar/Breo Ellipta (FF/VI,100/25mcg);  0.91 vs 1.07 per year; p<0.001 - 25% reduction for FF/UMEC/VI compared with Anoro Ellipta (UMEC/VI, 62.5/25mcg); 0.91 vs 1.21 per year; p<0.001
• In addition, statistically significant improvements were observed across all pre-specified key secondary endpoints and associated treatment comparisons:
• Change from baseline trough FEV1 at week 52 for FF/UMEC/VI compared with FF/VI was 97mL; p<0.001 and for FF/UMEC/VI compared with UMEC/VI was 54mL;
• Change from baseline St George’s Respiratory Questionnaire at week 52 for FF/UMEC/VI compared with FF/VI was -1.8 units; p<0.001 and for FF/UMEC/VI compared with UMEC/VI was -1.8 units;
• Analysis of time to first on-treatment moderate/severe COPD exacerbation demonstrated a 14.8% reduction in risk for FF/UMEC/VI compared with FF/VI; p<0.001, and a 16.0% reduction in risk for FF/UMEC/VI compared with UMEC/VI;
• Based on review of the headline data, the safety profile of FF/UMEC/VI was consistent with the known profile of the individual medicines and their dual combinations. The most common adverse events across the treatment groups were viral upper respiratory tract infection, worsening of COPD, upper respiratory tract infection, pneumonia and headache. The incidences of the most frequent serious adverse events were worsening of COPD: 11%, 11% and 13% for FF/UMEC/VI, FF/VI and UMEC/VI, respectively; and pneumonia: 4%, 4% and 3% for FF/UMEC/VI, FF/VI and UMEC/VI, respectively.
• Full results will be presented at upcoming scientific meetings and in peer-reviewed publications. Global regulatory filings with the IMPACT study are expected to commence in the second quarter of 2018 for consideration of expansion of the indicated patient population.
• • On July 16, 2014, GSK and Theravance announced the start of the IMPACT study, to evaluate the efficacy and safety of the 'closed' triple combination of FF/UMEC/VI in patients with chronic obstructive pulmonary disease (COPD). IMPACT is the first pivotal phase III study in a programme to evaluate a once-daily closed triple combination treatment of an inhaled corticosteroid (ICS); a long-acting muscarinic antagonist (LAMA); and a long-acting beta2-adrenergic agonist (LABA) in patients with COPD. The IMPACT study will enrol approximately 10,000 patients and assess whether the combination of fluticasone furoate, umeclidinium, and vilanterol, all delivered in GSK's Ellipta inhaler, can reduce the annual rate of moderate and severe exacerbations compared with two approved once daily COPD treatments, Relvar®/Breo® Ellipta® (fluticasone furoate + vilanterol), which is an ICS/LABA combination, and Anoro® Ellipta® (umeclidinium + vilanterol).

Is general: Yes