CC-chemokine ligand 2 inhibition in idiopathic pulmonary fibrosis: a phase 2 trial of carlumab.
Eur Respir J
; 46(6): 1740-50, 2015 Dec.
Article
em En
| MEDLINE
| ID: mdl-26493793
ABSTRACT
The objective of this study was to determine the safety and efficacy of carlumab in the treatment of idiopathic pulmonary fibrosis (IPF).A phase 2, randomised, double-blind placebo-controlled dose-ranging study was conducted in patients with IPF (n=126). Patients were randomised to carlumab (1â
mg·kg(-1), 5â
mg·kg(-1), or 15â
mg·kg(-1)) or placebo every 4â
weeks. The primary endpoint was the rate of percentage change in forced vital capacity (FVC). Secondary endpoints were time to disease progression, absolute change in FVC, relative change in diffusing capacity of the lung for carbon monoxide (DLCO), and St George's Respiratory Questionnaire (SGRQ) total score.Due to a pre-planned, unfavourable interim benefit-risk analysis, dosing was suspended. The rate of percentage change in FVC showed no treatment effect (placebo -0.582%, 1â
mg·kg(-1) -0.533%, 5â
mg·kg(-1) -0.799% and 15â
mg·kg(-1) -0.470%; p=0.261). All active treatment groups showed a greater decline in FVC (1â
mg·kg(-1) -290â
mL, 5â
mg·kg(-1) -370â
mL and 15â
mg·kg(-1) -320â
mL) compared with placebo (-130â
mL). No effect on disease progression, DLCO, infection rates or mortality was observed. SGRQ scores showed a nonsignificant trend toward worsening with active treatment. Unexpectedly, free CC-chemokine ligand 2 levels were elevated above baseline at both 24 and 52â
weeks. A higher proportion of patients with one or more serious adverse events was observed in the 5â
mg·kg(-1) group (53.1%) compared with 1â
mg·kg(-1) (15.2%), 15â
mg·kg(-1) (21.9%) and placebo (46.4%), although no unexpected serious adverse events were noted.Although dosing was stopped prematurely, it is unlikely that carlumab provides benefit to IPF patients.
Texto completo:
1
Coleções:
01-internacional
Contexto em Saúde:
2_ODS3
/
6_ODS3_enfermedades_notrasmisibles
Base de dados:
MEDLINE
Assunto principal:
Quimiocina CCL2
/
Fibrose Pulmonar Idiopática
/
Anticorpos Neutralizantes
/
Anticorpos Monoclonais
Tipo de estudo:
Clinical_trials
Aspecto:
Patient_preference
Limite:
Adult
/
Aged
/
Aged80
/
Female
/
Humans
/
Male
/
Middle aged
País/Região como assunto:
America do norte
/
Europa
Idioma:
En
Revista:
Eur Respir J
Ano de publicação:
2015
Tipo de documento:
Article