Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Clinical Trial
. 2014 Mar;13(2):148-55.
doi: 10.1016/j.jcf.2013.12.009. Epub 2014 Jan 17.

A randomized double blind, placebo controlled phase 2 trial of BIIL 284 BS (an LTB4 receptor antagonist) for the treatment of lung disease in children and adults with cystic fibrosis

Collaborators, Affiliations
Clinical Trial

A randomized double blind, placebo controlled phase 2 trial of BIIL 284 BS (an LTB4 receptor antagonist) for the treatment of lung disease in children and adults with cystic fibrosis

M W Konstan et al. J Cyst Fibros. 2014 Mar.

Abstract

Background: Airway inflammation, mediated in part by LTB4, contributes to lung destruction in patients with cystic fibrosis (CF). LTB(4)-receptor inhibition may reduce airway inflammation. We report the results of a randomized, double-blind, placebo-controlled study of the efficacy and safety of the leukotriene B(4) (LTB(4))-receptor antagonist BIIL 284 BS in CF patients.

Methods: CF patients aged ≥6 years with mild to moderate lung disease were randomized to oral BIIL 284 BS or placebo once daily for 24 weeks. Co-primary endpoints were change in FEV(1) and incidence of pulmonary exacerbation.

Results: After 420 (155 children, 265 adults) of the planned 600 patients were randomized, the trial was terminated after a planned interim analysis revealed a significant increase in pulmonary related serious adverse events (SAEs) in adults receiving BIIL 284 BS. Final analysis revealed SAEs in 36.1% of adults receiving BIIL 284 BS vs. 21.2% receiving placebo (p = 0.007), and in 29.6% of children receiving BIIL 284 BS vs. 22.9% receiving placebo (p = 0.348). In adults, the incidence of protocol-defined pulmonary exacerbation was greater in those receiving BIIL 284 BS than in those receiving placebo (33.1% vs. 18.2% respectively; p = 0.005). In children, the incidence of protocol-defined pulmonary exacerbation was 19.8% in the BIIL 284 BS arm, and 25.7% in the placebo arm (p = 0.38).

Conclusions: While the cause of increased SAEs and exacerbations due to BIIL 284 BS is unknown, the outcome of this trial provides a cautionary tale for the administration of potent anti-inflammatory compounds to individuals with chronic infections, as the potential to significantly suppress the inflammatory response may increase the risk of infection-related adverse events.

Keywords: Anti-inflammatory therapy; Clinical trial; Cystic fibrosis; Leukotriene B(4) receptor antagonist; Lung disease.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Subject Disposition, Consort Diagram
Figure 2
Figure 2
Time to Protocol-defined Pulmonary Exacerbation
Figure 3
Figure 3
Change in Lung Function

Comment in

  • Clinical Trials of Novel Treatments for Cystic Fibrosis.
    Hippolyte S, Pabary R, Waller M, Jones A, Simmonds N, Davies JC. Hippolyte S, et al. Am J Respir Crit Care Med. 2016 Mar 1;193(5):569-71. doi: 10.1164/rccm.201509-1734RR. Am J Respir Crit Care Med. 2016. PMID: 26765316 No abstract available.

References

    1. Cantin A. Cystic fibrosis lung inflammation: early, sustained, and severe. Am J Respir Crit Care Med. 1995;151:939–41. - PubMed
    1. Konstan MW, Berger M. Current understanding of the inflammatory process in cystic fibrosis - onset and etiology. Pediatr Pulmonol. 1997;24:137–42. - PubMed
    1. Döring G, Ratjen F. Immunology of cystic fibrosis. In: Hodson ME, Geddes D, Bush A, editors. Cystic Fibrosis. London, England: Arnold Hammer; 2007. pp. 69–80.
    1. Döring G, Conway SP, Heijerman HGM, et al. for the Consensus Committee. Antibiotic therapy against Pseudomonas aeruginosa in cystic fibrosis: a European consensus. Eur Respir J. 2000;16:749–767. - PubMed
    1. Konstan MW. Therapies aimed at airway inflammation in cystic fibrosis. In: Fiel SB, editor. Clinics in Chest Medicine: Cystic Fibrosis. Vol. 19. Philadelphia: W.B, Saunders Co; 1998. pp. 505–513. - PubMed

Publication types

MeSH terms