Clinical Trials

Date: 2016-09-06

Type of information: Presentation of results at a congress

phase: 3

Announcement: presentation of results at the European Respiratory Society International Congress

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

Product: combination of fluticasone furoate, umeclidinium and vilanterol (FF/UMEC/VI)

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: Inflammatory diseases - Respiratory diseases

Country:

Trial details:

• FULFIL (Lung FUnction and quality of LiFe assessment in COPD with closed trIpLe therapy) is a randomised, double-blind, double-dummy, parallel group multicentre study evaluating once-daily FF/UMEC/VI (100mcg/62.5mcg/25mcg) inhalation powder versus twice-daily budesonide/formoterol (400mcg/12mcg). The study aims to enrol 1,800 patients across approximately 180 study centres globally.
• The co-primary endpoints are: to evaluate the effects of FF/UMEC/VI on lung function and health related quality of life compared with budesonide/formoterol after 24 weeks of treatment. Other endpoints include the effect of FF/UMEC/VI on the annual rate of exacerbations compared with budesonide/formoterol, and the safety profile of FF/UMEC/VI compared with budesonide/formoterol over 24 weeks and 52 weeks of treatment. To provide additional longer term safety data, a sub-set of approximately 400 patients will remain on blinded study treatment for up to a total of 52 weeks.
• 1,810 patients were treated across 162 study centres globally (911 on FF/UMEC/VI and 899 on budesonide/formoterol). To provide additional longer term safety data, a sub-set of 430 patients remained on blinded study treatment for up to a total of 52 weeks.

Latest news:

• • On September 6, 2016, GSK and Innoviva announced the presentation of data from the pivotal phase III FULFIL study with investigational closed triple combination therapy fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI 100/62.5/25 mcg) in patients with chronic obstructive pulmonary disease (COPD), at the European Respiratory Society International Congress . The FULFIL study was designed to evaluate the effects of once daily FF/UMEC/VI compared with twice daily Symbicort® Turbohaler® (budesonide/formoterol 400/12 mcg) in patients with advanced COPD. It met its two co-primary endpoints. At 24 weeks, there was a clinically meaningful and statistically significant (p < 0.001) benefit for FF/UMEC/VI in both lung function, measured as mean change from baseline in trough FEV1 (171mL, 95% confidence interval [148, 194]) and health-related quality of life, measured as mean change from baseline in St George's Respiratory Questionnaire (SGRQ) total score (-6.6 units for closed triple versus -4.3 units for budesonide/formoterol, difference of -2.2 units, 95% confidence interval [-3.5, -1.0]). In addition, the proportion of patients who responded with the minimum clinically important difference in SGRQ (-4 units) was 50% on closed triple and 41% on budesonide/formoterol (odds ratio 1.41; p < 0.001). This benefit of treatment with closed triple therapy was also observed in the subset of patients who received treatment for up to 52 weeks, with a statistically significant improvement of 179mL in trough FEV1 and a numerical improvement of -2.7 units in SGRQ total score at Week 52 with closed triple therapy compared with budesonide/formoterol. The study also showed a statistically significant and clinically meaningful reduction in the annual rate of moderate/severe exacerbations with closed triple therapy compared to budesonide/formoterol, with closed triple therapy showing a 35% reduction versus budesonide/formoterol based on data up to 24 weeks and a 44% reduction in the subset of patients that received treatment for up to 52 weeks .
• The safety profile of the closed triple combination up to 24 weeks and in the subset of patients up to 52 weeks was consistent with the known profile of the individual medicines and their combinations. Up to both 24 weeks and 52 weeks, the most common adverse events in both treatment arms were nasopharyngitis, headache and COPD worsening.
• The incidence of investigator-reported serious adverse events for closed triple and budesonide/formoterol, respectively, was 5.4% and 5.7% up to 24 weeks, and 10.0% and 12.7% up to 52 weeks. Up to 24 weeks, the incidence of pneumonia was 1.0% in the closed triple arm and 0.3% in the budesonide/formoterol arm. Up to 52 weeks, it was 1.9% in the closed triple arm and 1.8% in the budesonide/formoterol arm. GSK's plans are on schedule for regulatory submissions of the closed triple combination therapy for COPD in the US and Europe by the end of 2016. • On February 9, 2015, GSK and Theravance announced the start of a second global phase III study to evaluate the effects of the investigational once-daily closed triple combination of fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) in patients with chronic obstructive pulmonary disease (COPD). Enrolling approximately 1,800 patients, the FULFIL study will assess whether the inhaled corticosteroid, long-acting muscarinic antagonist and long-acting beta2-adrenergic agonist (ICS/LAMA/LABA) combination, all delivered in GSK’s Ellipta® inhaler, can improve lung function and health-related quality of life compared with budesonide/formoterol, a twice-daily ICS/LABA combination delivered via the Turbohaler® dry powder inhaler.
• Secondary objectives include investigating the effect on the rate of exacerbations with FF/UMEC/VI compared with budesonide/formoterol, and the safety profile of FF/UMEC/VI compared with budesonide/formoterol. Adverse events of particular interest include pneumonia and cardiovascular risk. Patient perspectives of efficacy and physical activity will also be evaluated versus budesonide/formoterol.
• The first, larger study in the phase III programme, known as IMPACT, started in July 2014 to assess whether FF/UMEC/VI can reduce the rate of moderate and severe exacerbations compared with two approved once-daily COPD treatments, Relvar/Breo Ellipta (FF/VI), an ICS/LABA combination, and Anoro Ellipta (UMEC/VI), a LAMA/LABA combination.

Is general: Yes