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

Pneumonia Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02583373
• Other study ID #: CAL02-001
• Status: Completed
• Phase: Phase 1
• Start date: March 21, 2016
• Est. completion date: February 20, 2018

Study information

• Verified date: January 2020
• Source: Combioxin SA
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 19
• Est. completion date: February 20, 2018
• Est. primary completion date: February 20, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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.

Related Conditions & MeSH terms

• Pneumococcal Infections
• Pneumonia

Intervention

Drug:
• CAL02 Low-dose
Two doses of CAL02 (low-dose) administered 2 times (24 hours apart) as i.v. infusion
• CAL02 High-dose
Two doses of CAL02 (high-dose) administered 2 times (24 hours apart) as i.v. infusion
• Placebo
Placebo administered administered 2 times (24 hours apart) as i.v. infusion

Locations

Country	Name	City	State
Belgium	St Luc University Hospital	Brussels
Belgium	University Hospital Brussels	Brussels
Belgium	Clinique St Pierre	Ottignies
France	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	CH Yves Le Foll	Saint-Brieuc
France	CHRU de Tours	Tours

Sponsors (1)

Lead Sponsor	Collaborator
Combioxin SA

Countries where clinical trial is conducted

Belgium,  France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Frequency, severity and characteristics of adverse events after two iv. administrations of CAL02.	To determine the safety profile of CAL02	29 days
Secondary	Clinical efficacy: cure.	Complete resolution of signs and symptoms of pneumonia	29 days.
Secondary	Pharmacodynamic effects.	Measuring biomarkers (CRP/PCT).	29 days.
Secondary	Microbiological efficacy.	Eradication: baseline isolate not present in repeat culture from original infection site	29 days.
Secondary	Survival.	Assessment of 28 days all cause mortality.	29 days

External Links

•   CAL02, a novel antitoxin liposomal agent, in severe pneumococcal pneumonia: a first-in-human, double-blind, placebo-controlled, randomised trial
•   Lancet ID editorial: One step closer to precision medicine for infectious diseases