Safety and Efficacy Study of BT086 to Evaluate Adjunctive Therapy in sCAP

A Randomized, Double-blind, Placebo-controlled, Multicenter, Parallel-group, Adaptive Group-sequential Phase II Study, to Determine the Efficacy and Safety of BT086 as an Adjunctive Treatment in Severe Community Acquired Pneumonia (sCAP)

The purpose of this study is to determine whether the adjunctive therapy to standard antibiotic treatment of BT086 is safe and effective of decreasing the days patients require endotracheal ventilation due to Severe Community-Acquired Pneumonia (sCAP).

Severe Community-Acquired Pneumonia (sCAP) is usually defined clinically as pneumonia acquired from outside the hospital (CAP) that requires intensive medical care. Mortality of (s)CAP patients admitted to ICU range from 35-58% depending on time and admission of the patient and has not much improved in the last years.

BT086 contains a sufficient number of antibodies against the most frequent pathogens as well as antibodies against lipopolysaccharides and lipid A. Therefore, it can be assumed that administration of BT086 early in the clinical course of a severe infection such as sCAP may provide an effective adjunctive treatment to standard antibiotic therapy for sCAP patients.

Inclusion Criteria:

• Written informed consent:

  • given by the patient or
  • a legal/authorised representative of the patient or
  • a waiver for written informed consent due to emergency situation, in compliance with all local legal requirements.

• Male or female patients aged 18 years or older

• Patient receiving adequate antibiotic treatment for pneumonia

• Prior to endotracheal ventilation and therapy, the patient must have at least one of the following two signs of inflammation:

  • Fever/Hypothermia Fever defined as an oral, tympanic, oesophageal or vesical temperature of >38°C, tympanic temperature of >38°C or rectal temperature of >38.5°C, or hypothermia (rectal temperature <35.5°C) (measurement with temperature probe or device) or
  • White blood cell (WBC) count >10,000/mm³ or WBC <4,500/mm³

• Patient must have at least one of the following signs and symptoms of pneumonia:

  • New or increased cough
  • Production of purulent sputum or change in sputum characteristics
  • Dyspnoea or tachypnoea (respiratory rate >20 breaths/minute)
  • Pleuritic chest pain
  • Auscultatory findings on pulmonary examination of rales and/or crackles and/or evidence of pulmonary consolidation (e.g. dullness on percussion, bronchial breath sounds, or egophony)

• Radiological (or other imaging technique) evidence of (an) infiltrate(s) consistent with bacterial pneumonia

• Pneumonia has been acquired outside the hospital. In hospital-admitted patients, pneumonia has been diagnosed a maximum of 72 hours after admission. Patients from nursing homes or similar institutions are eligible.

• Major sCAP criterion: need for endotracheal ventilation

• Treatment of patient with BT086 must start within 12 hours but not earlier than 1 hour after start of endotracheal ventilation

Exclusion Criteria:

• For incapacitated patients: any indication that the patient's presumed will would be against inclusion in the trial
• Patients with suspected hospital-acquired pneumonia
• Severe lung diseases interfering with sCAP therapy e.g. patients with cystic fibrosis,
• Patients receiving Xigris® (drotrecogin alfa, activated Protein C) or medications not approved for sCAP (e.g. Dornase alpha) are excluded from inclusion in the study
• Patients on dialysis
• Presence of other severe diseases impairing life expectancy (e.g. patients are not expected to survive 28 days given their pre-existing uncorrectable medical condition).
• Patients unable to be treated due to obesity
• Selective, absolute IgA deficiency with known antibodies to IgA
• Patients with neutrophil count <1,000/mm³ or platelet count <50,000/mm³
• Pregnant or lactating women. A pregnancy test will be performed in all women aged <65 years and the result must be available at study inclusion.
• Known relevant intolerance to immunoglobulins, vaccines or other substances of human origin
• Participation in another interventional clinical trial within 30 days before entering the study or during the study, and/or previous participation in this study (participation in non-interventional trials is allowed).