Pneumonia Due to Staphylococcus AureusPhase 1/2NCT01589185
Safety, Pharmacokinetics and Efficacy of KBSA301 in Severe Pneumonia (S. Aureus)
A Phase 1/2 study testing KBSA301 in people with Pneumonia Due to Staphylococcus Aureus, run by Aridis Pharmaceuticals, Inc. at 18 sites in 4 countries.
Trial summary
The objectives of this study are to assess the safety, tolerability, pharmacokinetics, pharmacodynamics and clinical outcome of patients who have severe pneumonia caused by Staphylococcus aureus (S. aureus) after a single intravenous administration of KBSA301 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 Due to Staphylococcus Aureus
- What is being tested?
- KBSA301
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 48 participants
- Where
- 18 sitesin 4 countries
- Study dates
- May 2012to Sep 2016
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 ≤ 70 years of age
- Severe pneumonia caused by S. aureus (either methicillin-resistant or methicillin-sensitive) managed in an ICU
- APACHE II of ≤30 at the time of diagnosis
- Identification of S. aureus
- Written informed consent provided by the patient, the relatives or the designated trusted person and/or according to local guidelines
Who cannot join
- Women of child bearing potential are excluded from the participation from the study unless they have a negative pregnancy test at baseline and during the course of the study. Postmenopausal women or females that have been surgically sterilized are allowed to participate.
- Hypersensitivity to excipients or to any prescribed medication
- Severe neutropenia, lymphoma or anticipated chemotherapy
- Patients who have long-term tracheostomy
- Current or recent investigational drug (within 30 days of enrollment, or 5 half-lives of the investigational compound, whichever is longer)
- Presence of meningitis, endocarditis, or osteomyelitis
Show all 13Show fewer
- Acquired immune deficiency syndrome (AIDS) with cluster of differentiation 4 (CD4) count <200 cells/ml
- Known bronchial obstruction or a history of post-obstructive pneumonia.
- Active primary lung cancer or another malignancy metastatic to the lungs
- Cystic fibrosis, known or suspected Pneumocystis jiroveci pneumonia, or known or suspected active tuberculosis
- Immunosuppressive therapy
- Liver function deficiency
- Moribund clinical condition
Trial locations and contacts
18 sites in 4 countries.
18 sites in 4 countries
France11 sites
Site 41
Angers
Site 40
Angoulême
Site 32
Argenteuil
Site 34
Colombes
Site 36
Dijon
Site 35
La Roche-sur-Yon
Site 31
Limoges
Site 39
Lyon
Site 37
Nantes
Site 38
Orléans
Site 33
Tours
United States3 sites
Site 80
Houston, Texas, 77030
Site 83
Jacksonville, Florida, 32209
Site 81
Oklahoma City, Oklahoma, 73104
About this study
Official title: A Randomized, Double-blind, Placebo-controlled, Single Ascending Dose Study to Assess the Safety, Pharmacokinetics, Efficacy and Pharmacodynamics of KBSA301 in Severe Pneumonia (S. Aureus)
The objectives of this study are to assess the safety, tolerability, pharmacokinetics, pharmacodynamics and clinical outcome of patients who have severe pneumonia caused by Staphylococcus aureus (S. aureus) after a single intravenous administration of KBSA301 in addition of standard of care antibiotic treatment.
Read the detailed description
- aureus is a leading cause of bloodstream, skin, soft tissue, and lower respiratory tract infections worldwide. The frequencies of both nosocomial and community-acquired S. aureus infections have increased steadily over the years and the treatment of these infections has become more challenging due to the emergence of multi-drug resistant strains (e.g. methicillin-resistant Staphylococcus aureus).
- aureus has several virulence factors that contribute to the pathogenesis of the infection. Amongst them, alpha-toxin that is involved in the pathogenesis of pneumonia, as it leads to apoptosis and cell lysis, in particular lymphocytes, macrophages, alveolar epithelial cells, pulmonary endothelium, and thrombocytes.
In spite of preventive measures for S. aureus infections and current medical treatment (mostly antibiotic therapy, alone or in combination), there is a clear unmet medical need in the clinic for additional treatment options. Passive immunotherapy with monoclonal antibodies may improve treatment options for severe and life-threatening infections like those caused by S. aureus.
- Conditions
- Pneumonia Due to Staphylococcus Aureus
- Being tested
- KBSA301, Placebo
- Keywords
- Pneumonia, Monoclonal antibody, Staphylococcus aureus
- Medical subject headings
- Pneumonia, Staphylococcal Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
KBSA301Drug
Also called AR301
KBSA301 administered as a single intravenous infusion at dose 1, 2, 3 and 4.
PlaceboDrug
Also called Placebo KBSA301
Placebo administered as a single intravenous infusion
| Study group | Role | What they receive |
|---|---|---|
| KBSA301, a monoclonal antibody dose 1 | Experimental | 1 mg/kg KBSA301 Receives: Drug: KBSA301 |
| KBSA301, a monoclonal antibody dose 2 | Experimental | 3 mg/kg KBSA301 Receives: Drug: KBSA301 |
| KBSA301, a monoclonal antibody dose 3 | Experimental | 10 mg/kg KBSA301 Receives: Drug: KBSA301 |
| KBSA301, a monoclonal antibody dose 4 | Experimental | 20 mg/kg KBSA301 Receives: Drug: KBSA301 |
| Placebo | Experimental | KBSA301-placebo Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Efficacy Endpoint: All-Cause Mortality by Day 28
A summary of the number (%) of patients who died on or before Day 28 (mITT population) is provided, by treatment group and overall.
Measured: At Day 28 post infusion (Day 0)
Secondary outcomes (4)
Efficacy: All-Cause Mortality (End Of Study [EOS])
A summary of the number (%) of patients who died on or before timepoints Day EOS (mITT population) is provided, by treatment group (overall) and placebo.
Measured: Patients who died during the specified timepoints (by EOS), up to day 107
Efficacy: All-Cause Mortality (Day 14)
A summary of the number (%) of patients who died on or before timepoints Day 14 visit (mITT population) is provided, by treatment group (overall) and placebo.
Measured: Patients who died during the specified timepoints (Day 14)
Efficacy: All-Cause Mortality (Day 7)
A summary of the number (%) of patients who died on or before timepoints Day 7 visit (mITT population) is provided, by treatment group (overall) and placebo.
Measured: Patients who died during the specified timepoints (Day 7)
Efficacy: All-Cause Mortality (Day 21)
A summary of the number (%) of patients who died on or before timepoints Day 21 visit (mITT population) is provided, by treatment group (overall) and placebo.
Measured: Patients who died during the specified timepoints (Day 21)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 May 2012 (estimated)
- Study startMay 2012
- Primary completionMay 2016
- Study completionSep 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Pneumonia Due to Staphylococcus AureusStudies 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 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 48 participants (actual)
Sponsor and investigators
- Lead sponsor
- Aridis Pharmaceuticals, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Pierre-François M Laterre, MD, Principal investigator, Université catholique de Louvain, Brussels, Belgium
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01589185
- Sponsor's protocol ID
- KBSA301-001
- Status last verified
- Mar 2020
- First submitted
- 8 Apr 2012
- Last updated
- 24 Apr 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Francois B, Mercier E, Gonzalez C, Asehnoune K, Nseir S, Fiancette M, Desachy A, Plantefeve G, Meziani F, de Lame PA, Laterre PF; MASTER 1 study group. Safety and tolerability of a single administration of AR-301, a human monoclonal antibody, in ICU patients with severe pneumonia caused by Staphylococcus aureus: first-in-human trial. Intensive Care Med. 2018 Nov;44(11):1787-1796. doi: 10.1007/s00134-018-5229-2. Epub 2018 Oct 21.
PubMed 30343314
Study at a glance
From the registry record, last updated by the sponsor on 24 Apr 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Double-blind, Placebo-controlled, Single Ascending Dose Study to Assess the Safety, Pharmacokinetics, Efficacy and Pharmacodynamics of KBSA301 in Severe Pneumonia (S. Aureus)
- ClinicalTrials.gov ID
- NCT01589185
- Acronym / sponsor ID
- KBSA301-001
- Conditions
- Pneumonia Due to Staphylococcus Aureus
- Keywords
- Pneumonia, Monoclonal antibody, Staphylococcus aureus
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 48 participants (actual)
- Lead sponsor
- Aridis Pharmaceuticals, Inc.Industry (pharma, biotech, devices)
- Study start
- May 2012
- Primary completion
- May 2016 (actual)
- Study completion
- Sep 2016 (actual)
- First posted
- 1 May 2012 (estimated)
- Results
- Posted 8 Apr 2020
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, pharmacokinetics, pharmacodynamics and clinical outcome of patients who have severe pneumonia caused by Staphylococcus aureus (S. aureus) after a single intravenous administration of KBSA301 in addition of standard of care antibiotic treatment.
Detailed description
- aureus is a leading cause of bloodstream, skin, soft tissue, and lower respiratory tract infections worldwide. The frequencies of both nosocomial and community-acquired S. aureus infections have increased steadily over the years and the treatment of these infections has become more challenging due to the emergence of multi-drug resistant strains (e.g. methicillin-resistant Staphylococcus aureus).
- aureus has several virulence factors that contribute to the pathogenesis of the infection. Amongst them, alpha-toxin that is involved in the pathogenesis of pneumonia, as it leads to apoptosis and cell lysis, in particular lymphocytes, macrophages, alveolar epithelial cells, pulmonary endothelium, and thrombocytes.
In spite of preventive measures for S. aureus infections and current medical treatment (mostly antibiotic therapy, alone or in combination), there is a clear unmet medical need in the clinic for additional treatment options. Passive immunotherapy with monoclonal antibodies may improve treatment options for severe and life-threatening infections like those caused by S. aureus.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| KBSA301, a monoclonal antibody dose 1 | Experimental | Drug: KBSA3011 mg/kg KBSA301 |
| KBSA301, a monoclonal antibody dose 2 | Experimental | Drug: KBSA3013 mg/kg KBSA301 |
| KBSA301, a monoclonal antibody dose 3 | Experimental | Drug: KBSA30110 mg/kg KBSA301 |
| KBSA301, a monoclonal antibody dose 4 | Experimental | Drug: KBSA30120 mg/kg KBSA301 |
| Placebo | Experimental | Drug: PlaceboKBSA301-placebo |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Adult male or female patients ≥ 18 years and ≤ 70 years of age
- Severe pneumonia caused by S. aureus (either methicillin-resistant or methicillin-sensitive) managed in an ICU
- APACHE II of ≤30 at the time of diagnosis
- Identification of S. aureus
- Written informed consent provided by the patient, the relatives or the designated trusted person and/or according to local guidelines
Key exclusion criteria (13 listed)
- Women of child bearing potential are excluded from the participation from the study unless they have a negative pregnancy test at baseline and during the course of the study. Postmenopausal women or females that have been surgically sterilized are allowed to participate.
- Hypersensitivity to excipients or to any prescribed medication
- Severe neutropenia, lymphoma or anticipated chemotherapy
- Patients who have long-term tracheostomy
- Current or recent investigational drug (within 30 days of enrollment, or 5 half-lives of the investigational compound, whichever is longer)
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 |
|---|---|---|
| KBSA301Also: AR301KBSA301 administered as a single intravenous infusion at dose 1, 2, 3 and 4. | Drug | KBSA301, a monoclonal antibody dose 1, KBSA301, a monoclonal antibody dose 2, KBSA301, a monoclonal antibody dose 3, KBSA301, a monoclonal antibody dose 4 |
| PlaceboAlso: Placebo KBSA301Placebo administered as a single intravenous infusion | Drug | Placebo |
Primary outcome
Efficacy Endpoint: All-Cause Mortality by Day 28
Time frame: At Day 28 post infusion (Day 0)
A summary of the number (%) of patients who died on or before Day 28 (mITT population) is provided, by treatment group and overall.
4 secondary outcomes
Efficacy: All-Cause Mortality (End Of Study [EOS])
Time frame: Patients who died during the specified timepoints (by EOS), up to day 107
Efficacy: All-Cause Mortality (Day 14)
Time frame: Patients who died during the specified timepoints (Day 14)
Efficacy: All-Cause Mortality (Day 7)
Time frame: Patients who died during the specified timepoints (Day 7)
Efficacy: All-Cause Mortality (Day 21)
Time frame: Patients who died during the specified timepoints (Day 21)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Apr 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 30343314Francois B, Mercier E, Gonzalez C, Asehnoune K, Nseir S, Fiancette M, Desachy A, Plantefeve G, Meziani F, de Lame PA, Laterre PF; MASTER 1 study group. Safety and tolerability of a single administration of AR-301, a human monoclonal antibody, in ICU patients with severe pneumonia caused by Staphylococcus aureus: first-in-human trial. Intensive Care Med. 2018 Nov;44(11):1787-1796. doi: 10.1007/s00134-018-5229-2. Epub 2018 Oct 21.
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.
Pierre-François M Laterre, MD principal investigator
Université catholique de Louvain, Brussels, Belgium
18 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing KBSA301 in people with Pneumonia Due to Staphylococcus Aureus, run by Aridis Pharmaceuticals, Inc. at 18 sites in 4 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 5 inclusion and 13 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 24 Apr 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 18 sites in France, United States, Belgium, Spain. 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. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined 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.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 8 Apr 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Efficacy Endpoint: All-Cause Mortality by Day 28 (time frame: At Day 28 post infusion (Day 0)). 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 NCT01589185, 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 24 Apr 2020.