Clinical Trials

Date: 2017-12-11

Type of information: Results

phase: 2b

Announcement: results

Company: Mereo Biopharma (UK)

Product: BCT-197 (acumapimod)

Action mechanism:

• kinase inhibitor. BCT-197 (acumapimod) is an oral p38 MAP kinase inhibitor being developed as first-line acute therapy for acute exacerbations of chronic obstructive pulmonary disease. Acumapimod aims to address the airway and systemic inflammation that are characteristic drivers of the disease and to reduce the length of hospital stay.
• Prior to Mereo's acquisition of BCT-197, Novartis conducted five clinical trials in 459 patients and volunteers, including a Phase 2a trial in AECOPD patients that showed a clinically meaningful improvement in lung function and a statistically significant improvement in lung function at the highest doses.

 

Disease: acute exacerbations of chronic obstructive pulmonary disease

Therapeutic area: Infectious diseases - Respiratory diseases

Country:

Trial details:

• The Phase 2 dose-ranging clinical trial commenced in 2016. The trial was a randomised double blind, placebo-controlled parallel-group study assessing two dosing regimens of BCT-197 and placebo, in combination with Standard of Care, in 282 patients presenting with an acute exacerbation of COPD. Following baseline assessment, patients were randomised to receive a high dose or low dose regimen of BCT-197 or placebo on days 1, 3 and 5 of the study.
• The primary endpoint was a comparison of change in FEV1 from baseline to day seven within the treatment group. Patients were followed for 26 weeks in total.
• The secondary endpoints measured the area under the curve of FEV1 over time, time to normalization of FEV1, change from baseline over time in the EXACT-PRO score, time to and number of moderate/severe AECOPDs during the trial and the time a patient was in the hospital, measured from admission until the patient was medically fit for discharge.
• Following baseline assessment, 282 eligible patients were randomised to receive either two different dose regimens of BCT-197 or placebo (three doses over five days).

Latest news:  

• • On December 11, 2017, Mereo BioPharma announced positive top-line data from a Phase 2 clinical trial with BCT-197 (acumapimod)as a first-line therapy for acute exacerbations of chronic obstructive pulmonary disease (AECOPD). Primary endpoint (change in FEV1 from baseline to day 7 within the treatment group) and study objectives Primary endpoint met on an ITT basis for both BCT-197 high and low dose regimens (p= 0.012, p ? 0.001); no significant change from baseline (p=0.102) shown for Standard of Care plus placebo.
• One of the study objectives was the comparison between all three groups. This was not statistically significant however the treatment arms were numerically superior to the Standard of Care plus placebo arm. Secondary and exploratory endpoints Positive clinical and health economic outcomes supported by other secondary measures. Statistically significant reduction of more than 50% (p ? 0.027 to 0.05) in the number of clinical treatment failures, in the high dose group compared to Standard of Care plus placebo, as measured by the number of rehospitalisations for the treatment of COPD at days 90 through 150 and there was a trend seen as early as day 30. Trend demonstrating a 56% to 28% reduction from day 30 through day 150 in the broader composite clinical treatment failure scale (defined as requirement for additional antibiotics or corticosteroids during either the initial or subsequent reexacerbation, COPD rehospitalisation or death). This reduction was also observed in the high dose group (versus Standard of Care and low dose), consistent with the rehospitalisation data. Approximately 50% of the general COPD patient population have low blood eosinophils (less than 2%) and are considered steroid resistant. This group of patients (68% of patients in this study), when treated with BCT-197, demonstrated a trend in improvement in FEV1 from baseline at day 7. Standard of Care plus placebo showed almost no improvement in a prespecified subgroup analysis in this low blood eosinophil group.
• Safety: BCT-197 was reported to be safe and well tolerated with the incidence and nature of adverse events in line with expectations for this patient population. In particular, there were no BCT-197 induced liver injuries and only two cases of acneiform rash, both of which resolved.
• • On May 4, 2017, Mereo BioPharma announced, that it has successfully completed patient enrolment in the AETHER Phase 2 dose-ranging study of acumapimod (BCT-197), for the treatment of patients with acute exacerbations of chronic obstructive pulmonary disease (AECOPD).  A total of 282 patients have been enrolled to explore two different dosing regimens versus placebo, on top of standard of care, in patients presenting with an AECOPD in the hospital setting. The study aims to determine the most appropriate dosing regimen of acumapimod. The primary end point is forced expiratory volume in one second (FEV1). Following a 5-day dosing period, patients are being followed for 26 weeks to explore a number of additional end points including hospital stay times, patient reported outcomes and recurrence rates of AECOPD. Top-line data from this study is expected in the second half of 2017.

   

Is general: Yes