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

January 22, 2020 updated by: Combioxin SA

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

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.

Study Overview

Status

Completed

Conditions

Intervention / 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.

Study Type

Interventional

Enrollment (Actual)

19

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Belgium
      • Brussels, Belgium
        • University Hospital Brussels
      • Brussels, Belgium
        • St Luc University hospital
      • Ottignies, Belgium
        • Clinique St Pierre
  • France
      • Besancon, France
        • CHU Jean Minjoz
      • La Roche-sur-Yon, France
        • CHD Les Oudairies
      • Le Chesnay, France
        • Hôpital Mignot
      • Limoges, France
        • CHU Dupuytren
      • Orléans, France
        • Centre Hospitalier Régional d'Orléans
      • Saint-Brieuc, France
        • CH Yves Le Foll
      • Tours, France
        • CHRU de Tours

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years to 78 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Placebo Comparator: Placebo
Saline
Drug: Placebo
Placebo administered administered 2 times (24 hours apart) as i.v. infusion
Other Names:
  • Placebo CAL02
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 Names:
  • 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 Names:
  • CAL02 HD

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Frequency, severity and characteristics of adverse events after two iv. administrations of CAL02.
Time Frame: 29 days
To determine the safety profile of CAL02
29 days

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Clinical efficacy: cure.
Time Frame: 29 days.
Complete resolution of signs and symptoms of pneumonia
29 days.
Pharmacodynamic effects.
Time Frame: 29 days.
Measuring biomarkers (CRP/PCT).
29 days.
Microbiological efficacy.
Time Frame: 29 days.
Eradication: baseline isolate not present in repeat culture from original infection site
29 days.
Survival.
Time Frame: 29 days
Assessment of 28 days all cause mortality.
29 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Combioxin SA

Investigators

  • Principal Investigator: BRUNO FRANCOIS, MD, Centre Hospitalier Universitaire de Limoges CHU Dupuytren 2 Avenue Martin Luther King 87042 Limoges Cedex, France

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 21, 2016

Primary Completion (Actual)

February 20, 2018

Study Completion (Actual)

February 20, 2018

Study Registration Dates

First Submitted

October 19, 2015

First Submitted That Met QC Criteria

October 20, 2015

First Posted (Estimate)

October 22, 2015

Study Record Updates

Last Update Posted (Actual)

January 27, 2020

Last Update Submitted That Met QC Criteria

January 22, 2020

Last Verified

January 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CAL02-001

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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