E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
severe Community Acquired Pneumonia (sCAP) |
|
E.1.1.1 | Medical condition in easily understood language |
severe Pneumonia (sCAP) acquired outside the hospital |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Respiratory Tract Diseases [C08] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10010120 |
E.1.2 | Term | Community acquired pneumonia |
E.1.2 | System Organ Class | 100000004862 |
|
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
Main objective of this clinical phase II trial is to evaluate the efficacy (ventilator free days) of BT086 IgM concentrate in patients with sCAP (severe community acquired pneumonia) |
|
E.2.2 | Secondary objectives of the trial |
Secondary objectives of this clinical phase II trial are to demonstrate repeated dose safety, tolerability, pharmacodynamic and pharmacokinetics of BT086 intravenous administration.
Pharmacodynamics: Evaluation of complement system (6 patients) and Procalcitonin and C-reactive protein (CRP)
Pharmacokinetics (PK): Evaluation of IgM and serum concentration of IgM, IgA, IgG in approximately 20 patients
Evaluation of safety and tolerability in terms of:
• Infusion-related reactions
• Adverse events (AEs)
• Vital signs
• Electrocardiogram (ECG)
• Safety laboratory
|
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. 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.
2. Male or female patients aged 18 years or older
3. Patient receiving adequate antibiotic treatment for pneumonia
4. 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, 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
5. 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)
6. Radiological (or other imaging technique) evidence of (an) infiltrate(s) consistent
with bacterial pneumonia
7. 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.
8. Major sCAP criterion: need for endotracheal ventilation
9. Treatment of patient with BT086 must start within 12 hours but not earlier
than 1 hour after start of endotracheal ventilation
|
|
E.4 | Principal exclusion criteria |
1. For incapacitated patients: any indication that the patient’s presumed will would
be against inclusion in the trial
2. Patients with suspected hospital-acquired pneumonia
3. Severe lung diseases interfering with sCAP therapy e.g. patients with
cystic fibrosis,
4. 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
5. Patients on dialysis
6. 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).
7. Patients unable to be treated due to obesity
8. Selective, absolute IgA deficiency with known antibodies to IgA
9. Patients with neutrophil count <1,000/mm³ or platelet count <50,000/mm³
10. 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.
11. Known relevant intolerance to immunoglobulins, vaccines or other substances
of human origin
12. 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).
|
|
E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint is the increase of ventilator free days (VFDs) measured in sCAP patients treated with adjunctive BT086 and the appropriate standard of care treatment compared to patients treated with placebo and the appropriate standard of care.
|
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
E.5.2 | Secondary end point(s) |
Furthermore the following secondary endpoints will be assessed.
• VFDs in surviving patients
• 28-day all cause mortality
• 28-day pneumonia cause mortality
• Time to discharge from ICU (intensive care unit)
• Time to discharge from hospital
• SOFA score
• Glasgow coma score
• Vasopressor-free days
|
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
adaptive group-sequential |
|
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 20 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 30 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
Last visit of last subject (chapter 13.2 of the study protocol) |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 4 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 4 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |