Conditions: Pulmonary Disease, Chronic Obstructive
Keywords: Phase II clinical study losmapimod exacerbations COPD eosinophil sub-group
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 184
Healthy volunteers: no

Brief summary:
This is a randomised, double-blind, parallel-group, multi-centre study evaluating 15 milligram (mg) twice daily/ Bi-daily (BID) of losmapimod versus placebo, in addition to standard of care (SoC).

The primary objective of this study is to explore the therapeutic potential of losmapimod as a treatment to reduce the rate of exacerbations in the subset of participants with moderate-to-severe COPD who are at high risk of exacerbation, having experienced two or more moderate/severe exacerbations in the preceding 12 months, and who have \<=2% of blood eosinophils at screening. As secondary objectives safety, effects on lung function, quality of life, pharmacokinetic (PK), biomarkers of both disease and inflammation shall be evaluated.

The duration of the treatment period is variable but will be at least 26 weeks and up to a maximum of 52 weeks, with the end of study date being established once the final participant has been randomized. The purpose of the variable dosing regimen is to enable participants to remain in the study for a longer duration, as it is anticipated that this will increase the likelihood of observing exacerbation events without increasing the overall study duration. It will also enable safety data on dosing periods beyond 6 months to be generated.

Approximately 200 participants in a 1:1 ratio between losmapimod and placebo will be randomized to the study. Sample size re-estimation will be performed during the course of the study to potentially increase the sample size up to a maximum of 600 participants.

Detailed description:

Arms:
arm 1: Subjects with COPD will receive losmapimod 15 mg tablets orally, twice daily, approximately 12 hours apart and within 30 minutes after meals with a full glass of water for the duration of the treatment period in addition to standard of care, stratified according to whether a center collects sputum or not and current use of inhaled corticosteroid (ICS). Salbutamol metered dose inhaler (MDI) will be provided as a rescue medication. arm 2: Subjects with COPD will receive placebo orally, twice daily, approximately 12 hours apart and within 30 minutes after meals with a full glass of water for the duration of the treatment period in addition to standard of care, stratified according to whether a center collects sputum or not and current use of ICS. Salbutamol MDI will be provided as a rescue medication.

Interventions: intervention 1: Losmapimod tablets intervention 2: Placebo tablets intervention 3: Salbutamol MDI
Intervention descriptions: intervention 1: Losmapimod tablets will be provided as 15 mg strength in a formulation containing lactose. Administered orally, twice daily approximately 12 hours apart and with food and water for the duration of the treatment period. Participants will be instructed to take their medication with a full glass of water twice-daily within 30 minutes after meals for the duration of their treatment period. intervention 2: Placebo tablets will be provided in a formulation containing lactose and visually matching the losmapimod tablets. Administered orally, twice daily approximately 12 hours apart and with food and water for the duration of the treatment period. Participants will be instructed to take their medication with a full glass of water twice-daily within 30 minutes after meals for the duration of their treatment period intervention 3: Salbutamol MDI will be provided as a rescue medication.

Protocol document: