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

Phase 1

Completed

• Conditions: Pneumonia; Pneumococcal Infections
• Interventions: Drug: CAL02 Low-dose; Drug: CAL02 High-dose; Drug: Placebo

• Registration Number: NCT02583373
• Lead Sponsor: Combioxin SA

Brief Summary

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

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.

Study Timeline

• Study First Submitted: 2015-10-19
• Study First Submitted QC: 2015-10-20
• Study First Posted: 2015-10-22
• Study Start: 2016-03-21
• Primary Completion: 2018-02-20
• Study Completion: 2018-02-20
• Status Verified: 2020-01
• Last Update Submitted: 2020-01-22
• Last Update Posted: 2020-01-27

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 19

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
CAL02 Low-dose	CAL02 Low-dose	Liposomal formulation
CAL02 High-dose	CAL02 High-dose	Liposomal formulation
Placebo	Placebo	Saline

Primary Outcome Measures

Name	Time	Method
Frequency, severity and characteristics of adverse events after two iv. administrations of CAL02.	29 days	To determine the safety profile of CAL02

Secondary Outcome Measures

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

Trial Locations

Locations (10)

University Hospital Brussels; 🇧🇪 Brussels, Belgium

Clinique St Pierre; 🇧🇪 Ottignies, Belgium

CHU Jean Minjoz; 🇫🇷 Besancon, France

CHD Les Oudairies; 🇫🇷 La Roche-sur-Yon, France

Hôpital Mignot; 🇫🇷 Le Chesnay, France

CHU Dupuytren; 🇫🇷 Limoges, France

Centre Hospitalier Régional d'ORLEANS; 🇫🇷 Orléans, France

CHRU de Tours; 🇫🇷 Tours, France

St Luc University Hospital; 🇧🇪 Brussels, Belgium

CH Yves Le Foll; 🇫🇷 Saint-Brieuc, France