SB-681323 IV for Subjects at Risk of Acute Lung Injury or ARDS
Condition: Lung Injury, Acute
MeSH terms: Respiratory Distress Syndrome; Acute Lung Injury; Lung Injury; Wounds and Injuries
Study type: Interventional
Phase: Phase 2

Summary: 
      This is an early phase (Phase IIa), randomized, double-blind, parallel group, multi-centre
      study for subjects with trauma (physical injury) who are at risk for developing Acute Lung
      Injury (ALI) or Acute Respiratory Distress Syndrome (ARDS). The primary purpose of the study
      is to evaluate the safety and tolerability of SB-681323, which is a potent, selective
      inhibitor of p38 alpha (MAPK) (prevents inflammation of tissue), in comparison to a placebo.
    

Detailed description: 
      The acute respiratory distress syndrome (ARDS) is a form of severe lung injury (ALI)
      characterized by hypoxemic respiratory failure (the lungs are unable to absorb oxygen to the
      arterial blood) and non-cardiogenic pulmonary edema (accumulation of fluid in the lungs). The
      syndrome may be caused by direct or indirect injury to the lungs. It is associated with a
      mortality rate of up to 40-50%. There are no marketed pharmacologic therapies for this
      devastating syndrome.

      This study aims to assess the safety and tolerability of SB-681323, which is a potent,
      selective inhibitor of p38 alpha mitogen-activated protein kinase.

      The rationale behind the development of this drug is that there are elevated levels of
      circulating pro-inflammatory agents, such as cytokines which are biological agents that
      increase levels of inflammation in the lungs. These agents are part of an 'inflammatory loop'
      and it may be beneficial to the condition to dampen this loop.

      p38 mitogen activated protein kinase (MAPK) plays a major role in the regulation and
      activation of intracellular proteins which are subsequently involved in the regulation of the
      cytokines. The pathway is activated by 'stress', such as injury, causing the inflammation.
      Therefore, 'dampening' this system should reduce the level of inflammation.

      This study will investigate the anti-inflammatory activity, efficacy (effectiveness at
      achieving the desired effect) and safety of SB-681323.

      To measure the efficacy of the drug, biomarkers will be measured. Biomarkers are biological
      agents in the body that are effected by the presence of specific injury or inflammation and
      are directly or indirectly linked to a regulatory system of event in the body. They are used
      to measure for the presence and severity of the condition in question. This study will
      investigate biomarkers linked directly or indirectly to the p38 alpha regulatory
      mechanism/system. We will be measuring biomarkers such as serum inflammatory biomarkers,
      coagulation (blood clotting) system biomarkers, biomarkers of endothelial cell / neutrophil
      interaction and biomarkers of lung epithelial cell injury.
    

Intervention name(s): SB-681323 Intravenous 3mg; SB-681323 Intravenous 7.5 mg; SB-681323 Intravenous 7.5mg; SB-681323 Intravenous 10mg; Placebo
Intervention type(s): Drug; Drug; Drug; Drug; Other
Intervention description(s): 3 mg SB-681323 Intravenous administration infused over 4 hours; 7.5 mg SB-681323 Intravenous administration infused over 24 hours; 7.5 mg SB-681323 Intravenous administration infused over 4 hours; 10 mg SB-681323 Intravenous administration infused over 24 hours; Placebo to match intervention
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary purpose: Treatment
Keywords: dilmapimod; p38; SB-681323; Acute Lung Injury (ALI); Acute Respiratory Distress Syndrome (ARDS)