Search

Abstract Background Interleukin-1 receptor 1 (IL-1R1) inhibition is a potential strategy for treating patients with chronic obstructive pulmonary disease (COPD). MEDI8968, a fully human monoclonal antibody, binds selectively to IL-1R1, inhibiting activation by IL-1α and IL-1β. We studied the efficacy and safety/tolerability of MEDI8968 in adults with symptomatic, moderate-to-very severe COPD. Methods This was a phase II, randomised, double-blind, placebo-controlled, multicentre, parallel-group study. Subjects aged 45–75 years and receiving standard maintenance 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 exacerbations of COPD (AECOPD) rate (week 56 post-randomisation). Secondary endpoints were severe AECOPD rate and St George’s Respiratory Questionnaire-COPD (SGRQ-C) score (week 56 post-randomisation). Results Of subjects randomised to placebo (n = 164) and MEDI8968 (n = 160), 79.3% and 75.0%, respectively, completed the study. There were neither statistically significant differences between treatment groups in moderate/severe AECOPD rate ([90% confidence interval]: 0.78 [0.63, 0.96], placebo; 0.71 [0.57, 0.90], MEDI8968), nor in severe AECOPD rate or SGRQ-C scores. Post-hoc 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 similar. 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, NCT01448850 , date of registration: 06 October 2011.

Background: Interleukin-1 receptor 1 (IL-1R1) inhibition is a potential strategy for treating patients with chronic obstructive pulmonary disease (COPD). MEDI8968, a fully human monoclonal antibody, binds selectively to IL-1R1, inhibiting activation by IL-1α and IL-1β. We studied the efficacy and safety/tolerability of MEDI8968 in adults with symptomatic, moderate-to-very severe COPD.Methods: This was a phase II, randomised, double-blind, placebo-controlled, multicentre, parallel-group study. Subjects aged 45-75 years and receiving standard maintenance 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 exacerbations of COPD (AECOPD) rate (week 56 post-randomisation). Secondary endpoints were severe AECOPD rate and St George's Respiratory Questionnaire-COPD (SGRQ-C) score (week 56 post-randomisation).Results: Of subjects randomised to placebo (n = 164) and MEDI8968 (n = 160), 79.3% and 75.0%, respectively, completed the study. There were neither statistically significant differences between treatment groups in moderate/severe AECOPD rate ([90% confidence interval]: 0.78 [0.63, 0.96], placebo; 0.71 [0.57, 0.90], MEDI8968), nor in severe AECOPD rate or SGRQ-C scores. Post-hoc 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 similar. 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, NCT01448850 , date of registration: 06 October 2011. [ABSTRACT FROM AUTHOR]

Introduction: Hidradenitis suppurativa is a chronic skin disease with a significant unmet need for treatment options. Randomized controlled trials are few and only a single drug (adalimumab) has Hidradenitis as a registered indication., Areas Covered: The clinicaltrials.gov and the EudraCT clinical trials register for reported trials on Hidradenitis Suppurativa was searched on the 22-06-2017. Trials for upcoming new drugs for HS are reported focusing on drugs in phase I and II trials.The clinicaltrials.gov and the EudraCT clinical trials register for reported trials on Hidradenitis Suppurativa was searched on the 22-06-2017. Trials for upcoming new drugs for HS are reported focusing on drugs in phase I and II trials., Expert Opinion: Currently, MABp1, Secukinumab, CJM112, Apremilast and IFX-1 are being investigated in Phase I and II trials and offer theoretical and promising new treatment options. A trial with the drug MEDI8968 has been terminated with disappointing results. Metformin, Botulinum Toxin B, Provodine, Benzoyl Peroxide and intralesional triamcinolone are being tested as well. Treatment of Hidradenitis remains a challenge and quality RTCs are needed. Studies indicates a range of potential targets for therapy such as interleukin-1 and interleukin-17, but 'broad-spectrum' immunosuppressants like phosphodiesterase-4 inhibitors are being examined as well. A range of outcomes, including Physician Global Assessment, Sartorius scores and hidradenitis suppurativa clinical response are used in these trials, making future meta-analysis of the data difficult.