Safety, Tolerability, Efficacy and Pharmacodynamics of CAL02 in Severe Pneumonia Caused by Streptococcus Pneumoniae
Primary Purpose
Pneumonia, Pneumococcal Infections
Status
Completed
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
CAL02 Low-dose
CAL02 High-dose
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Pneumonia focused on measuring Pneumonia, Streptococcus pneumoniae, Pneumolysin
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.
Sites / Locations
- St Luc University Hospital
- University Hospital Brussels
- Clinique St Pierre
- CHU Jean Minjoz
- CHD Les Oudairies
- Hôpital Mignot
- CHU Dupuytren
- Centre Hospitalier Régional d'ORLEANS
- CH Yves Le Foll
- CHRU de Tours
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Active Comparator
Active Comparator
Placebo Comparator
Arm Label
CAL02 Low-dose
CAL02 High-dose
Placebo
Arm Description
Liposomal formulation
Liposomal formulation
Saline
Outcomes
Primary Outcome Measures
Frequency, severity and characteristics of adverse events after two iv. administrations of CAL02.
To determine the safety profile of CAL02
Secondary Outcome Measures
Clinical efficacy: cure.
Complete resolution of signs and symptoms of pneumonia
Pharmacodynamic effects.
Measuring biomarkers (CRP/PCT).
Microbiological efficacy.
Eradication: baseline isolate not present in repeat culture from original infection site
Survival.
Assessment of 28 days all cause mortality.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02583373
Brief Title
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
2. Study Status
Record Verification Date
January 2020
Overall Recruitment Status
Completed
Study Start Date
March 21, 2016 (Actual)
Primary Completion Date
February 20, 2018 (Actual)
Study Completion Date
February 20, 2018 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Combioxin SA
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Pneumonia, Pneumococcal Infections
Keywords
Pneumonia, Streptococcus pneumoniae, Pneumolysin
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
19 (Actual)
8. Arms, Groups, and Interventions
Arm Title
CAL02 Low-dose
Arm Type
Active Comparator
Arm Description
Liposomal formulation
Arm Title
CAL02 High-dose
Arm Type
Active Comparator
Arm Description
Liposomal formulation
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Saline
Intervention Type
Drug
Intervention Name(s)
CAL02 Low-dose
Other Intervention Name(s)
CAL02 LD
Intervention Description
Two doses of CAL02 (low-dose) administered 2 times (24 hours apart) as i.v. infusion
Intervention Type
Drug
Intervention Name(s)
CAL02 High-dose
Other Intervention Name(s)
CAL02 HD
Intervention Description
Two doses of CAL02 (high-dose) administered 2 times (24 hours apart) as i.v. infusion
Intervention Type
Drug
Intervention Name(s)
Placebo
Other Intervention Name(s)
Placebo CAL02
Intervention Description
Placebo administered administered 2 times (24 hours apart) as i.v. infusion
Primary Outcome Measure Information:
Title
Frequency, severity and characteristics of adverse events after two iv. administrations of CAL02.
Description
To determine the safety profile of CAL02
Time Frame
29 days
Secondary Outcome Measure Information:
Title
Clinical efficacy: cure.
Description
Complete resolution of signs and symptoms of pneumonia
Time Frame
29 days.
Title
Pharmacodynamic effects.
Description
Measuring biomarkers (CRP/PCT).
Time Frame
29 days.
Title
Microbiological efficacy.
Description
Eradication: baseline isolate not present in repeat culture from original infection site
Time Frame
29 days.
Title
Survival.
Description
Assessment of 28 days all cause mortality.
Time Frame
29 days
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
BRUNO FRANCOIS, MD
Organizational Affiliation
Centre Hospitalier Universitaire de Limoges CHU Dupuytren 2 Avenue Martin Luther King 87042 Limoges Cedex, France
Official's Role
Principal Investigator
Facility Information:
Facility Name
St Luc University Hospital
City
Brussels
Country
Belgium
Facility Name
University Hospital Brussels
City
Brussels
Country
Belgium
Facility Name
Clinique St Pierre
City
Ottignies
Country
Belgium
Facility Name
CHU Jean Minjoz
City
Besancon
Country
France
Facility Name
CHD Les Oudairies
City
La Roche-sur-Yon
Country
France
Facility Name
Hôpital Mignot
City
Le Chesnay
Country
France
Facility Name
CHU Dupuytren
City
Limoges
Country
France
Facility Name
Centre Hospitalier Régional d'ORLEANS
City
Orléans
Country
France
Facility Name
CH Yves Le Foll
City
Saint-Brieuc
Country
France
Facility Name
CHRU de Tours
City
Tours
Country
France
12. IPD Sharing Statement
Citations:
PubMed Identifier
31056427
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.
Results Reference
derived
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Safety, Tolerability, Efficacy and Pharmacodynamics of CAL02 in Severe Pneumonia Caused by Streptococcus Pneumoniae
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