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

Community Acquired Pneumonia Clinical Trial

— CIGMA  

Official title:

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01420744
• Other study ID #: CIGMA Study 982
• Status: Completed
• Phase: Phase 2
• First received: August 19, 2011
• Last updated: July 28, 2015
• Start date: August 2011
• Est. completion date: April 2015

Study information

• Verified date: July 2015
• Source: Biotest
• Contact: n/a
• Is FDA regulated: No
• Health authority: Germany: Paul-Ehrlich-InstitutSpain: Agencia Española de Medicamentos y Productos SanitariosBelgium: Federal Agency for Medicines and Health Products, FAMHPUnited Kingdom: Medicines and Healthcare Products Regulatory Agency
• Study type: Interventional

Clinical Trial Summary

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).

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 160
• Est. completion date: April 2015
• Est. primary completion date: February 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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).

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Community Acquired Pneumonia
• Pneumonia

Intervention

Drug:
• BT086
BT086 will be administered per intravenous infusion (IV). The dose to be administered is 3.65 mL /kg bw/day and is calculated by the mean Immunoglobulin M (IgM) content of BT086 which is 23%. Infusion rate: Starting rate is 0.1 mL/min. Maximum infusion rate is 0.5 mL/min (target infusion rate) Treatment will be administered over a 5-day period.
• 1% Human Albumin infusion
1% Albumin will be administered per intravenous infusion (IV). The dose to be administered is 3.65 mL /kg bw/day. Infusion rate:Starting rate is 0.1 mL/min. Maximum infusion rate is 0.5 mL/min (target infusion rate). Rate is to be raised in steps of 0.1 mL every 10 min until the target infusion rate is reached. Treatment will be administered over a 5-day period. Starting rate is 0.1 mL/min. Maximum infusion rate is 0.5 mL/min (target infusion rate)

Locations

Country	Name	City	State
Belgium	401	Brussels
Germany	108	Berlin
Germany	114	Chemnitz
Germany	110	Dresden
Germany	111	Erfurt
Germany	116	Frankfurt
Germany	117	Greifswald
Germany	103	Halle
Germany	115	Hamburg
Germany	101	Hannover
Germany	107	Homburg/Saar
Germany	118	Köln
Germany	119	Köln
Germany	109	Lübeck
Germany	106	Marburg
Germany	120	Stuttgart
Germany	105	Tübingen
Germany	113	Wuppertal
Spain	213	Badalona
Spain	201	Barcelona
Spain	206	Barcelona
Spain	204	Girona
Spain	207	Madrid
Spain	208	Mataro
Spain	210	Palma de Mallorca
Spain	212	Sabadell
Spain	209	Santiago de Compostela
Spain	205	Tarragona
Spain	211	Terrassa
Spain	203	Valencia
United Kingdom	303	Cardiff
United Kingdom	304	Kings Lynn, Norfolk
United Kingdom	301	London
United Kingdom	306	London
United Kingdom	302	Poole, Dorset
United Kingdom	305	Reading, Berkshire

Sponsors (1)

Lead Sponsor	Collaborator
Biotest

Countries where clinical trial is conducted

Belgium,  Germany,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Ventilator Free Days (VFDs)	VFDs are defined as the number of days between successful weaning from endotracheal ventilation and day 28 after study enrolment.	28 days	No
Secondary	28-day all cause mortality	All patients will be classified as either "alive at Study Day 28" or, if dead, "dead at Study Day 28", regardless of cause of death.	28 days (672 hours from randomization)	No
Secondary	28-day pneumonia-cause mortality	All patients will be classified as either "alive at Study Day 28" or, if dead, "dead at Study Day 28, with pneumonia as cause of death".	28 days (672 hours from randomization)	No
Secondary	Time (days) to discharge from ICU	The date and time of admission to and discharge from the ICU will be recorded in the Case Report Form (CRF). The time to discharge from the ICU will be calculated as the number of days spent in the ICU.	28 days	No
Secondary	Time (days) to discharge from hospital	The date and time of admission to and discharge from the hospital will be recorded in the CRF. The time to discharge from the hospital will be calculated as the number of days spent in the hospital.	28 days	No
Secondary	SOFA: Score Sequential Organ Failure Assessment	Each organ system (cardiovascular, haematology, hepatic, renal, respiratory) will be scored using the SOFA methodology.For analysis, a patient will receive a score on each day (Study Days 1-7, Day 14, Day 21, and Day 28). Mean changes in organ function scores over time and percentages of patients whose organ function has resolved will be compared between treatment groups.	28 days	No
Secondary	Vasopressor-free days	Vasopressor-free days will be calculated in a similar manner to VFDs, as described above. Vasopressors include dobutamine, epinephrine, dopamine, and norepinephrine.; A day is considered as a vasopressor-free day if a patient does not receive; Dobutamine >2.5 µg/kg/min or/and; Epinephrine (adrenalin) >=2.5 µg/min or/and; Dopamine >=2.5 µg/kg/min or/and; Norepinephrine >=0.014 µg/kg/min for 4 hours per day.	28 days	No
Secondary	Glasgow Coma Score	The Glasgow Coma Scale will be scored using the Glasgow Coma Score methodology. The patient will be assessed by calculating the score on each study day (Day -1 through to Day 28).	28 days	No