Safety, Tolerability, Efficacy and Pharmacodynamics of CAL02 in Severe Pneumonia Caused by Streptococcus Pneumoniae

Study Overview
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Brief Summary
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The objectives of this study are to assess the safety, tolerability, clinical and microbiological efficacy and pharmacodynamics of patients who have severe pneumonia caused by Streptococcus pneumoniae after the intravenous administration of CAL02 in addition of standard of care antibiotic treatment.

Detailed Description
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Streptococcus pneumoniae is the most frequently identified pathogen of community-acquired bacterial pneumonia and its severe forms are associated with high morbidity and mortality, despite pneumococcal vaccines and medical treatment (antibiotic therapy, alone or in combination). Bacterial toxins, such as the pore-forming toxin (PFT) pneumolysin (from Streptococcus pneumoniae), are involved in the development of invasive disease and play a key role in severe and fatal complications. CAL02 offers a novel therapeutic approach by neutralising bacterial toxins, such as pneumolysin, which recognise specific microdomains on host cell membranes, called lipid rafts.

Official Title
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Randomised, Multicentre, Double-blind, Placebo-controlled Study to Assess the Safety, Efficacy and Pharmacodynamics After the Intravenous Administration of CAL02 in Severe Community-acquired Pneumonia Due to Streptococcus Pneumoniae

Conditions
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Pneumonia, Pneumococcal Infections

Intervention / Treatment
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* Drug: CAL02 Low-dose
* Drug: CAL02 High-dose
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult male or female patients ≥ 18 years and ≤ 80 years of age Body weight 40-140 kg Severe pneumonia caused by Streptococcus pneumoniae managed in an ICU CURB-65 score ≥ 3 in patients aged > 65 and CURB-65 ≥ 2 in patients aged < 65 Streptococcus pneumoniae identification with the urine antigen test or any other proven documented identification method Written informed consent provided by the patient, the relatives or the designated trusted person and/or according to local guidelines Exclusion Criteria: Patients with hospital-acquired-, health care-acquired- or ventilator- associated-pneumonia More than (i) 12 hours since diagnosis of severe CAPP and (ii) 24 hours or 60 hours since antibiotic treatment IV or per os, respectively, unless documented not to be active against S. pneumoniae, will have elapsed at the time of IMP administration APACHE II score > 30 points SOFA score > 12 points Inability to maintain a mean arterial pressure ≥ 50 mm Hg Known hypersensitivity to liposomal formulations Patients with severe neutropenia or lymphoma or current or anticipated chemotherapy End-stage neuromuscular disorders Patients who have long-term tracheostomy Current or recent participation in an investigational study Presence of other pneumococcal site infection Patients with known acquired immune deficiency syndrome (AIDS) with CD4 count < 200 cells/mL Patients with known post-obstructive pneumonia (active primary lung cancer or another malignancy metastatic to the lungs) Patients with cystic fibrosis, Pneumocystis jiroveci pneumonia, or active tuberculosis Patients receiving immunosuppressant therapy Patients with a known liver function deficiency Splenectomised patients Patients who have experienced an allergic reaction to eggs Moribund clinical condition Nursing and pregnant women Women of child bearing potential not using an effective contraception.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: CAL02 Low-dose<br>Liposomal formulation | Drug: CAL02 Low-dose<br>* Two doses of CAL02 (low-dose) administered 2 times (24 hours apart) as i.v. infusion<br>* Other names: CAL02 LD;|
| Active Comparator: CAL02 High-dose<br>Liposomal formulation | Drug: CAL02 High-dose<br>* Two doses of CAL02 (high-dose) administered 2 times (24 hours apart) as i.v. infusion<br>* Other names: CAL02 HD;|
| Placebo Comparator: Placebo<br>Saline | Drug: Placebo<br>* Placebo administered administered 2 times (24 hours apart) as i.v. infusion<br>* Other names: Placebo CAL02;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Frequency, severity and characteristics of adverse events after two iv. administrations of CAL02. | To determine the safety profile of CAL02 | 29 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical efficacy: cure. | Complete resolution of signs and symptoms of pneumonia | 29 days. | 
| Pharmacodynamic effects. | Measuring biomarkers (CRP/PCT). | 29 days. | 
| Microbiological efficacy. | Eradication: baseline isolate not present in repeat culture from original infection site | 29 days. | 
| Survival. | Assessment of 28 days all cause mortality. | 29 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pneumonia, Streptococcus pneumoniae, Pneumolysin