PneumoniaPhase 1NCT02583373
Safety, Tolerability, Efficacy and Pharmacodynamics of CAL02 in Severe Pneumonia Caused by Streptococcus Pneumoniae
A Phase 1 study testing CAL02 Low-dose and CAL02 High-dose in people with Pneumonia and Pneumococcal Infections, run by Combioxin SA at 10 sites in 2 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Pneumonia, Pneumococcal Infections
- What is being tested?
- CAL02 Low-dose and CAL02 High-dose
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 19 participants
- Where
- 10 sitesin 2 countries
- Study dates
- 21 Mar 2016to 20 Feb 2018
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 21Show fewer
- 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.
Trial locations and contacts
10 sites in 2 countries.
10 sites in 2 countries
France7 sites
CHU Jean Minjoz
Besançon
CHD Les Oudairies
La Roche-sur-Yon
Hôpital Mignot
Le Chesnay
CHU Dupuytren
Limoges
Centre Hospitalier Régional d'ORLEANS
Orléans
CH Yves Le Foll
Saint-Brieuc
CHRU de Tours
Tours
Belgium3 sites
St Luc University Hospital
Brussels
University Hospital Brussels
Brussels
Clinique St Pierre
Ottignies
About this study
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
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.
Read the 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.
- Conditions
- Pneumonia, Pneumococcal Infections
- Being tested
- CAL02 Low-dose, CAL02 High-dose, Placebo
- Keywords
- Pneumonia, Streptococcus pneumoniae, Pneumolysin
- Medical subject headings
- Pneumonia, Pneumococcal Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CAL02 Low-doseDrug
Also called CAL02 LD
Two doses of CAL02 (low-dose) administered 2 times (24 hours apart) as i.v. infusion
CAL02 High-doseDrug
Also called CAL02 HD
Two doses of CAL02 (high-dose) administered 2 times (24 hours apart) as i.v. infusion
PlaceboDrug
Also called Placebo CAL02
Placebo administered administered 2 times (24 hours apart) as i.v. infusion
| Study group | Role | What they receive |
|---|---|---|
| CAL02 Low-dose | Active comparator | Liposomal formulation Receives: Drug: CAL02 Low-dose |
| CAL02 High-dose | Active comparator | Liposomal formulation Receives: Drug: CAL02 High-dose |
| Placebo | Placebo comparator | Saline Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Frequency, severity and characteristics of adverse events after two iv. administrations of CAL02.
To determine the safety profile of CAL02
Measured: 29 days
Secondary outcomes (4)
Clinical efficacy: cure.
Complete resolution of signs and symptoms of pneumonia
Measured: 29 days.
Pharmacodynamic effects.
Measuring biomarkers (CRP/PCT).
Measured: 29 days.
Microbiological efficacy.
Eradication: baseline isolate not present in repeat culture from original infection site
Measured: 29 days.
Survival.
Assessment of 28 days all cause mortality.
Measured: 29 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Oct 2015 (estimated)
- Study start21 Mar 2016
- Primary completion20 Feb 2018
- Study completion20 Feb 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for PneumoniaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 19 participants (actual)
Sponsor and investigators
- Lead sponsor
- Combioxin SA
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- BRUNO FRANCOIS, MD, Principal investigator, Centre Hospitalier Universitaire de Limoges CHU Dupuytren 2 Avenue Martin Luther King 87042 Limoges Cedex, France
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02583373
- Sponsor's protocol ID
- CAL02-001
- Status last verified
- Jan 2020
- First submitted
- 19 Oct 2015
- Last updated
- 27 Jan 2020
- Results posted
- No
- Data monitoring committee
- Yes
Publications
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.
PubMed 31056427
Study at a glance
From the registry record, last updated by the sponsor on 27 Jan 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT02583373
- Acronym / sponsor ID
- CAL02-001
- Conditions
- Pneumonia, Pneumococcal Infections
- Keywords
- Pneumonia, Streptococcus pneumoniae, Pneumolysin
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 19 participants (actual)
- Lead sponsor
- Combioxin SAIndustry (pharma, biotech, devices)
- Study start
- 21 Mar 2016 (actual)
- Primary completion
- 20 Feb 2018 (actual)
- Study completion
- 20 Feb 2018 (actual)
- First posted
- 22 Oct 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| CAL02 Low-dose | Active comparator | Drug: CAL02 Low-doseLiposomal formulation |
| CAL02 High-dose | Active comparator | Drug: CAL02 High-doseLiposomal formulation |
| Placebo | Placebo comparator | Drug: PlaceboSaline |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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
Key exclusion criteria (21 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CAL02 Low-doseAlso: CAL02 LDTwo doses of CAL02 (low-dose) administered 2 times (24 hours apart) as i.v. infusion | Drug | CAL02 Low-dose |
| CAL02 High-doseAlso: CAL02 HDTwo doses of CAL02 (high-dose) administered 2 times (24 hours apart) as i.v. infusion | Drug | CAL02 High-dose |
| PlaceboAlso: Placebo CAL02Placebo administered administered 2 times (24 hours apart) as i.v. infusion | Drug | Placebo |
Primary outcome
Frequency, severity and characteristics of adverse events after two iv. administrations of CAL02.
Time frame: 29 days
To determine the safety profile of CAL02
4 secondary outcomes
Clinical efficacy: cure.
Time frame: 29 days.
Pharmacodynamic effects.
Time frame: 29 days.
Microbiological efficacy.
Time frame: 29 days.
Survival.
Time frame: 29 days
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Jan 2020.
- Derived from this study: PubMed 31056427Laterre 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.
- Lancet ID editorial: One step closer to precision medicine for infectious diseasesLink provided by the sponsor.
Related trials for Pneumonia
Not yet recruitingPhase 1
Phase I Open-Label Safety Trial of Pembrolizumab for Neurological Post- Acute Sequelae of SARS-CoV-2 (PD1-PASC I)
Post-Acute COVID-19 Syndrome
Not yet recruitingPhase 2/3
A Pivotal Safety and Immunogenicity GBS-NN/NN2 Vaccine Maternal Immunisation Trial
Streptococcus Agalactiae Infection, Neonatal Sepsis
Active, not recruitingPhase 1
A Safety and Immunogenicity Trial of OCU500, ChAd36 Vector Encoding SARS-CoV-2 Spike Vaccine Via Intranasal and Inhalational Routes in Previously Vaccinated Adults
COVID-19
Enrolling by invitation
Personalized Ventilator Settings for Patients on ECMO
Acute Respiratory Distress Syndrome (ARDS), Extracorporeal Membrane Oxygenation
Not yet recruiting
Expanded Diagnostic Strategy in Older Adults Hospitalized With Community-Acquired Acute Respiratory Infection
Acute Respiratory Infection
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
BRUNO FRANCOIS, MD principal investigator
Centre Hospitalier Universitaire de Limoges CHU Dupuytren 2 Avenue Martin Luther King 87042 Limoges Cedex, France
10 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing CAL02 Low-dose and CAL02 High-dose in people with Pneumonia and Pneumococcal Infections, run by Combioxin SA at 10 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 27 Jan 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 10 sites in France, Belgium. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Frequency, severity and characteristics of adverse events after two iv. administrations of CAL02. (time frame: 29 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02583373, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Jan 2020.