Clinical trial NCT02583373: Safety, Tolerability, Efficacy and Pharmacodynamics of CAL02 in Severe Pneumonia Caused by Streptococcus Pneumoniae
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Pneumonia
Pneumococcal Infections
Keywords: Pneumonia
Streptococcus pneumoniae
Pneumolysin
Lead sponsor: Combioxin SA
Sponsor class: INDUSTRY
First posted: 2015-10-22
Enrollment: 19
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Frequency, severity and characteristics of adverse events after two iv. administrations of CAL02.
timeFrame: 29 days
Secondary outcomes:
measure: Clinical efficacy: cure.
timeFrame: 29 days.
measure: Pharmacodynamic effects.
timeFrame: 29 days.
measure: Microbiological efficacy.
timeFrame: 29 days.
measure: Survival.
timeFrame: 29 days
Other outcomes:
Locations:
city: Brussels
country: Belgium
facility: St Luc University Hospital
city: Brussels
country: Belgium
facility: University Hospital Brussels
city: Ottignies
country: Belgium
facility: Clinique St Pierre
city: Besancon
country: France
facility: CHU Jean Minjoz
city: La Roche-sur-Yon
country: France
facility: CHD Les Oudairies
city: Le Chesnay
country: France
facility: Hôpital Mignot
city: Limoges
country: France
facility: CHU Dupuytren
city: Orléans
country: France
facility: Centre Hospitalier Régional d'ORLEANS
city: Saint-Brieuc
country: France
facility: CH Yves Le Foll
city: Tours
country: France
facility: CHRU de Tours
Study officials:
affiliation: Centre Hospitalier Universitaire de Limoges CHU Dupuytren 2 Avenue Martin Luther King 87042 Limoges Cedex, France
name: BRUNO FRANCOIS, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Laterre PF, Colin G, Dequin PF, Dugernier T, Boulain T, Azeredo da Silveira S, Lajaunias F, Perez A, Francois B. CAL02, a novel antitoxin liposomal agent, in severe pneumococcal pneumonia: a first-in-human, double-blind, placebo-controlled, randomised trial. Lancet Infect Dis. 2019 Jun;19(6):620-630. doi: 10.1016/S1473-3099(18)30805-3. Epub 2019 May 2.