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

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ClinicalTrials.gov Identifier: NCT02583373
Recruitment Status : Completed
First Posted : October 22, 2015
Last Update Posted : January 27, 2020
Information provided by (Responsible Party):
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.

Condition or disease Intervention/treatment Phase
Pneumonia Pneumococcal Infections Drug: CAL02 Low-dose Drug: CAL02 High-dose Drug: Placebo Phase 1

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 19 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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
Actual Study Start Date : March 21, 2016
Actual Primary Completion Date : February 20, 2018
Actual Study Completion Date : February 20, 2018

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Pneumonia

Arm Intervention/treatment
Active Comparator: CAL02 Low-dose
Liposomal formulation
Drug: CAL02 Low-dose
Two doses of CAL02 (low-dose) administered 2 times (24 hours apart) as i.v. infusion
Other Name: CAL02 LD

Active Comparator: CAL02 High-dose
Liposomal formulation
Drug: CAL02 High-dose
Two doses of CAL02 (high-dose) administered 2 times (24 hours apart) as i.v. infusion
Other Name: CAL02 HD

Placebo Comparator: Placebo
Drug: Placebo
Placebo administered administered 2 times (24 hours apart) as i.v. infusion
Other Name: Placebo CAL02

Primary Outcome Measures :
  1. Frequency, severity and characteristics of adverse events after two iv. administrations of CAL02. [ Time Frame: 29 days ]
    To determine the safety profile of CAL02

Secondary Outcome Measures :
  1. Clinical efficacy: cure. [ Time Frame: 29 days. ]
    Complete resolution of signs and symptoms of pneumonia

  2. Pharmacodynamic effects. [ Time Frame: 29 days. ]
    Measuring biomarkers (CRP/PCT).

  3. Microbiological efficacy. [ Time Frame: 29 days. ]
    Eradication: baseline isolate not present in repeat culture from original infection site

  4. Survival. [ Time Frame: 29 days ]
    Assessment of 28 days all cause mortality.

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02583373

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St Luc University Hospital
Brussels, Belgium
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
CH Yves Le Foll
Saint-Brieuc, France
CHRU de Tours
Tours, France
Sponsors and Collaborators
Combioxin SA
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Principal Investigator: BRUNO FRANCOIS, MD Centre Hospitalier Universitaire de Limoges CHU Dupuytren 2 Avenue Martin Luther King 87042 Limoges Cedex, France
Additional Information:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Combioxin SA
ClinicalTrials.gov Identifier: NCT02583373    
Other Study ID Numbers: CAL02-001
First Posted: October 22, 2015    Key Record Dates
Last Update Posted: January 27, 2020
Last Verified: January 2020
Keywords provided by Combioxin SA:
Streptococcus pneumoniae
Additional relevant MeSH terms:
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Pneumonia, Pneumococcal
Pneumococcal Infections
Respiratory Tract Infections
Lung Diseases
Respiratory Tract Diseases
Streptococcal Infections
Gram-Positive Bacterial Infections
Bacterial Infections
Bacterial Infections and Mycoses
Pneumonia, Bacterial