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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 : Recruiting
First Posted : October 22, 2015
Last Update Posted : July 24, 2017
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.

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 24 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
Study Start Date : March 2016
Estimated Primary Completion Date : January 2018
Estimated Study Completion Date : June 2018

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Pneumonia
U.S. FDA Resources

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, Senior)
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

Contact: ANTONIO PEREZ, MD +41228108372 toni.perez@combioxin.com
Contact: SAMAREH AZEREDO DA SILVEIRA LAJAUNIAS, PhD +41228108372 samareh.lajaunias@combioxin.com

St Luc University Hospital Recruiting
Brussels, Belgium
Contact: Pierre-François LATERRE, Prof.         
University Hospital Brussels Recruiting
Brussels, Belgium
Contact: Herbert SPAPEN, MD         
Clinique St Pierre Recruiting
Ottignies, Belgium
Contact: Thierry DUGERNIER, MD         
CHU Jean Minjoz Recruiting
Besancon, France
Contact: Jean-Christophe NAVELLOU, MD         
CHD Les Oudairies Recruiting
La Roche-sur-Yon, France
Contact: Gwenhael COLIN, MD         
Hôpital Mignot Recruiting
Le Chesnay, France
Contact: Jean-Pierre Bedos, MD         
CHU Dupuytren Recruiting
Limoges, France
Contact: Bruno FRANCOIS, MD         
Centre Hospitalier Régional d'ORLEANS Recruiting
Orléans, France
Contact: Thierry BOULAIN, MD         
CH Yves Le Foll Recruiting
Saint-Brieuc, France
Contact: Anne COURTE, MD         
CHRU de Tours Recruiting
Tours, France
Contact: Pierre-François DEQUIN, Prof         
Sponsors and Collaborators
Combioxin SA
Principal Investigator: BRUNO FRANCOIS, MD Centre Hospitalier Universitaire de Limoges CHU Dupuytren 2 Avenue Martin Luther King 87042 Limoges Cedex, France

Responsible Party: Combioxin SA
ClinicalTrials.gov Identifier: NCT02583373     History of Changes
Other Study ID Numbers: CAL02-001
First Posted: October 22, 2015    Key Record Dates
Last Update Posted: July 24, 2017
Last Verified: July 2017

Keywords provided by Combioxin SA:
Streptococcus pneumoniae

Additional relevant MeSH terms:
Pneumococcal Infections
Pneumonia, Pneumococcal
Lung Diseases
Respiratory Tract Diseases
Respiratory Tract Infections
Streptococcal Infections
Gram-Positive Bacterial Infections
Bacterial Infections
Pneumonia, Bacterial