Klebsiella Pneumoniae InfectionPhase 1/2NCT04959344
Safety and Immunogenicity of a Klebsiella Pneumoniae Tetravalent Bioconjugate Vaccine (Kleb4V)
A Phase 1/2 study testing Kleb4V target dose, Kleb4V target dose + AS03 and Kleb4V low dose in people with Klebsiella Pneumoniae Infection, run by LimmaTech Biologics AG at 2 sites in Germany.
Trial summary
In this study, the tetravalent bioconjugate candidate vaccine Kleb4V will be tested to obtain first-time-in-human (FTIH) data on its safety and immunogenicity in healthy adults. Read more about this study
- Who is it for?
- Ages 18 to 70 yearsHealthy volunteers can take part
- Conditions the study is for
- Klebsiella Pneumoniae Infection
- What is being tested?
- Kleb4V target dose, Kleb4V target dose + AS03 and Kleb4V low dose
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 166 participants
- Where
- 2 sitesGermany
- Study dates
- 5 Jul 2021to 26 Sep 2022
- Phase
- Phase 1/2
- 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 70 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Good general health by medical history, laboratory findings and physical examination before receiving vaccination as judged by the investigator (subjects with a minor controlled illness, such as mild controlled hypertension, asthma or COPD (Chronic Obstructive Pulmonary Disease), and without fever may be enrolled at the discretion of the investigator)
- Subject who is willing and able to comply with the requirements of the protocol (e.g. completion of the diary cards, return for follow-up visits)
- Signed written informed consent obtained from the subject
- For Step 1 Groups 1 and 2 only: Female or male between 18-40 years (inclusive) of age
- For Step 1 Groups 3 to 6, and Step 2: Female or male subjects between 55-70 (inclusive) years of age at the time of first vaccination
- Female subjects of childbearing potential are eligible, as long as they practice adequate contraceptive measures from 2 months before the first vaccination until 1 month after the last vaccination.
Who cannot join
- Health condition that, in the opinion of the investigator, may interfere with optimal participation in the study or place the volunteer at increased risk of adverse events (AEs) Study clinicians, in consultation with the principal investigator, will use clinical judgement on a case-by-case basis to assess safety risks under this criterion
- Any clinically significant deviation from the normal range in biochemistry or hematology blood tests in the opinion of the investigator
- Clinically significant abnormalities on physical examination
- Suspected or known hypersensitivity (including allergy) to any of the vaccine components or to medicinal products or medical equipment whose use is foreseen in this study
- History of allergy to any vaccine
- Clinical conditions representing a contraindication to intramuscular vaccination and blood draws (e.g. coagulation disorder)
Show all 26Show fewer
- Acute or chronic, clinically significant cardiovascular, pulmonary, hepatic or renal abnormality diseases and/or insufficiency as determined by physical examination or laboratory tests. In particular: unstable current or history of coronary artery disease or cardiac insufficiency, uncontrolled hypertension, clinically significant history of myocardial infarction, atrial fibrillation, uncontrolled or clinically significant type 2 diabetes, current or history of rheumatoid arthritis or temporal arteritis, current acute or chronic active pulmonary diseases.
- Note: Subjects may be on chronic or as needed medications if, in the opinion of the site principal investigator or appropriate sub-investigator, they pose no additional risk to subject safety or assessment of reactogenicity and immunogenicity and do not indicate a worsening of medical diagnosis or condition
- Known or suspected impairment of immunological function, documented Human Immunodeficiency Virus (HIV) infection, asplenia/splenectomy, or history of autoimmune disease or lymphoproliferative disorder
- Positive blood test for HBsAg, HCV (Hepatitis C Virus), HIV-1/2
- Positive test for SARS-CoV-2 (severe acute respiratory syndrome coronavirus type 2)
- History of systemic administration of immunosuppressive drugs, i.e. corticosteroids, (PO/IV/IM) within the last 4 weeks prior to 1st vaccination or for more than 14 consecutive days within 3 months prior to 1st vaccination, until the last blood sampling visit (i.e. prednisone or equivalent ≥20 mg/day). Inhaled and topical steroids are allowed.
- Administration of anti-neoplastic and immune-modulating agents or chemotherapy within 90 days prior to informed consent
- Planned administration of a vaccine not foreseen by the study protocol within 4 weeks prior to 1st vaccination and 4 weeks after last vaccination. Vaccination against seasonal influenza virus (or CoVID (Coronavirus disease) vaccine if on the market) is allowed outside of +/- 7 days from each vaccination
- Concurrently participating in another clinical study, at any time during the study period, in which the subject has been or will be exposed to an investigational or a non-investigational interventional vaccine/product (pharmaceutical product)
- Body Mass Index (BMI) <19 and >30
- History of any chronic or progressive disease that according to judgement of the investigator could interfere with the study outcomes or pose a threat to the participant's health
- Received an investigational or non-registered product (medicinal drug or vaccine), other than the study vaccine within 3 months prior to 1st administration of study vaccine, or planned use during the study period
- Administration of immunoglobulin and/or any blood products within the three months preceding the first dose of study vaccine
- Blood donation of at least 500 mL blood draw within 3 months preceding injection or planned during the study period as reported by subject
- Use of any antibiotic therapy within 1 week preceding each injection
- Subjects with an elective surgical intervention, planned during the study period until 30 days after 2nd vaccination
- Females lactating, or pregnancy or intention to become pregnant as reported by subject
- Current and/or history of chronic alcohol consumption and/or drug abuse
- History of immune-mediated disease (see Table of pIMDs (potential Immune Mediated Diseases) in Annex).
- Heavy smokers (> 20 cigarettes per day)
Trial locations and contacts
2 sites in 1 country.
Germany2 sites
Nuvisan GmbH, Standort Gauting, Robert-Koch-Allee 29
Gauting, 82131
Nuvisan GmbH, Standort Neu-Ulm, Wegenerstrasse 13
Neu-Ulm, 89231
About this study
Official title: Safety and Immunogenicity of a Klebsiella Pneumoniae Tetravalent Bioconjugate Vaccine (Kleb4V) Administered to Healthy Adults: A FTIH Phase I/II Randomized and Controlled Study
In this study, the tetravalent bioconjugate candidate vaccine Kleb4V will be tested to obtain first-time-in-human (FTIH) data on its safety and immunogenicity in healthy adults.
Read the detailed description
Kleb4V is a tetravalent bioconjugate vaccine including O antigen-polysaccharides of the most predominant Klebsiella pneumoniae serotypes, which will be formulated with or without Adjuvant System, AS03. Study participants will be randomized towards Kleb4V Low dose with or without AS03, Kleb4V Target dose with or without AS03, or placebo.
The study will be conducted in two steps. In Step1 (safety cohort): safety and tolerability of Kleb4V without and with Adjuvant AS03 will be evaluated first in adults of 18-40 y, and subsequently in the target population of older adults 55-70 y. Enrolment will be staggered in groups of small numbers to the different doses and formulations.
In Step 2 (target cohort): Older adults (55-70y) will be concomitantly randomized to receive 1 of the 4 different vaccine formulations or placebo.
- Conditions
- Klebsiella Pneumoniae Infection
- Being tested
- Kleb4V target dose, Kleb4V target dose + AS03, Kleb4V low dose, Kleb4V low dose + AS03, Placebo
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Kleb4V target doseBiological
Two doses of the non-adjuvanted Kleb4V target dose will be administered intramuscularly 2 months apart
Kleb4V target dose + AS03Biological
Two doses of the adjuvanted Kleb4V target dose will be administered intramuscularly 2 months apart
Kleb4V low doseBiological
Two doses of the non-adjuvanted Kleb4V low dose will be administered intramuscularly 2 months apart
Kleb4V low dose + AS03Biological
Two doses of the adjuvanted Kleb4V low dose will be administered intramuscularly 2 months apart
PlaceboBiological
Two doses of the Placebo will be administered intramuscularly 2 months apart
| Study group | Role | What they receive |
|---|---|---|
| Kleb4V target dose | Experimental | Study participants receive 2 target doses of the non-adjuvanted investigational product 2 months apart. Receives: Biological: Kleb4V target dose |
| Kleb4V target dose + AS03 | Experimental | Study participants receive 2 target doses of the adjuvanted investigational product 2 months apart. Receives: Biological: Kleb4V target dose + AS03 |
| Kleb4V low dose | Experimental | Study participants receive 2 low doses of the non-adjuvanted investigational product 2 months apart. Receives: Biological: Kleb4V low dose |
| Kleb4V low dose + AS03 | Experimental | Study participants receive 2 low doses of the adjuvanted investigational product 2 months apart. Receives: Biological: Kleb4V low dose + AS03 |
| Placebo (Diluent) | Placebo comparator | Study participants receive 2 doses of the Placebo 2 months apart. Receives: Biological: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety: Occurrence, severity and relationship of solicited local and general AEs (Adverse Events)
Occurrence, severity and relationship of solicited local and general AEs (Adverse Events)
Measured: during 7 days following each vaccination
Safety: Occurrence, severity and relationship of unsolicited AEs
Occurrence, severity and relationship of unsolicited AEs
Measured: during 28 days following each vaccination
Safety: Occurrence, severity and relationship of medically relevant AEs, AESIs and SAEs
Occurrence, severity and relationship of medically relevant AEs, AESIs (Adverse Events of Special Interest) and SAEs (Serious Adverse Events)
Measured: through the study completion, on average of 1 year
Immunogenicity: IgG (Immunoglobulin G) titers against the Klebsiella pneumoniae O serotypes included in the vaccine
For each active group vs. placebo: Comparison of geometric mean titers (GMTs) of serum IgG against the four K. pneumoniae O-serotypes included in Kleb4V.
Measured: between baseline and 28 days after the second injection
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Jul 2021
- Study start5 Jul 2021
- Primary completion26 Sep 2022
- Study completion26 Sep 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Klebsiella Pneumoniae InfectionStudies 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
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 166 participants (actual)
Sponsor and investigators
- Lead sponsor
- LimmaTech Biologics AG
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- GlaxoSmithKline
- Responsible party
- Sponsor
- Investigators
- Cristina Alaimo, Study director, LimmaTech Biologics AGSteffen Haffner, Dr, Principal investigator, Nuvisan GmbH
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04959344
- Sponsor's protocol ID
- Kleb4V01
- Status last verified
- Oct 2022
- First submitted
- 25 Jun 2021
- Last updated
- 4 Oct 2022
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Alaimo C, Karaky N, Lawrence R, Bownes E, Haffner S, Kowarik M, Goldblatt D, Martin P. Safety and Immunogenicity of a Klebsiella pneumoniae Tetravalent Bioconjugate Vaccine (Kleb4V) Administered to Healthy Adults: A First-in-Human Phase I/II Randomized and Controlled Study. J Infect Dis. 2026 Feb 18;233(2):e342-e351. doi: 10.1093/infdis/jiaf600.
PubMed 41289032Chen Z, Gou Q, Yuan Y, Zhang X, Zhao Z, Liao J, Zeng X, Jing H, Jiang S, Zhang W, Zeng H, Huang W, Zou Q, Zhang J. Vaccination with a trivalent Klebsiella pneumoniae vaccine confers protection in a murine model of pneumonia. Vaccine. 2024 Oct 3;42(23):126217. doi: 10.1016/j.vaccine.2024.126217. Epub 2024 Aug 19.
PubMed 39163713
Study at a glance
From the registry record, last updated by the sponsor on 4 Oct 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Safety and Immunogenicity of a Klebsiella Pneumoniae Tetravalent Bioconjugate Vaccine (Kleb4V) Administered to Healthy Adults: A FTIH Phase I/II Randomized and Controlled Study
- ClinicalTrials.gov ID
- NCT04959344
- Acronym / sponsor ID
- Kleb4V01
- Conditions
- Klebsiella Pneumoniae Infection
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 166 participants (actual)
- Lead sponsor
- LimmaTech Biologics AGIndustry (pharma, biotech, devices)
- Collaborators
- GlaxoSmithKline
- Study start
- 5 Jul 2021 (actual)
- Primary completion
- 26 Sep 2022 (actual)
- Study completion
- 26 Sep 2022 (actual)
- First posted
- 13 Jul 2021 (actual)
- 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.
In this study, the tetravalent bioconjugate candidate vaccine Kleb4V will be tested to obtain first-time-in-human (FTIH) data on its safety and immunogenicity in healthy adults.
Detailed description
Kleb4V is a tetravalent bioconjugate vaccine including O antigen-polysaccharides of the most predominant Klebsiella pneumoniae serotypes, which will be formulated with or without Adjuvant System, AS03. Study participants will be randomized towards Kleb4V Low dose with or without AS03, Kleb4V Target dose with or without AS03, or placebo.
The study will be conducted in two steps. In Step1 (safety cohort): safety and tolerability of Kleb4V without and with Adjuvant AS03 will be evaluated first in adults of 18-40 y, and subsequently in the target population of older adults 55-70 y. Enrolment will be staggered in groups of small numbers to the different doses and formulations.
In Step 2 (target cohort): Older adults (55-70y) will be concomitantly randomized to receive 1 of the 4 different vaccine formulations or placebo.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| Kleb4V target dose | Experimental | Biological: Kleb4V target doseStudy participants receive 2 target doses of the non-adjuvanted investigational product 2 months apart. |
| Kleb4V target dose + AS03 | Experimental | Biological: Kleb4V target dose + AS03Study participants receive 2 target doses of the adjuvanted investigational product 2 months apart. |
| Kleb4V low dose | Experimental | Biological: Kleb4V low doseStudy participants receive 2 low doses of the non-adjuvanted investigational product 2 months apart. |
| Kleb4V low dose + AS03 | Experimental | Biological: Kleb4V low dose + AS03Study participants receive 2 low doses of the adjuvanted investigational product 2 months apart. |
| Placebo (Diluent) | Placebo comparator | Biological: PlaceboStudy participants receive 2 doses of the Placebo 2 months apart. |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Good general health by medical history, laboratory findings and physical examination before receiving vaccination as judged by the investigator (subjects with a minor controlled illness, such as mild controlled hypertension, asthma or COPD (Chronic Obstructive Pulmonary Disease), and without fever may be enrolled at the discretion of the investigator)
- Subject who is willing and able to comply with the requirements of the protocol (e.g. completion of the diary cards, return for follow-up visits)
- Signed written informed consent obtained from the subject
- For Step 1 Groups 1 and 2 only: Female or male between 18-40 years (inclusive) of age
- For Step 1 Groups 3 to 6, and Step 2: Female or male subjects between 55-70 (inclusive) years of age at the time of first vaccination
Key exclusion criteria (26 listed)
- Health condition that, in the opinion of the investigator, may interfere with optimal participation in the study or place the volunteer at increased risk of adverse events (AEs) Study clinicians, in consultation with the principal investigator, will use clinical judgement on a case-by-case basis to assess safety risks under this criterion
- Any clinically significant deviation from the normal range in biochemistry or hematology blood tests in the opinion of the investigator
- Clinically significant abnormalities on physical examination
- Suspected or known hypersensitivity (including allergy) to any of the vaccine components or to medicinal products or medical equipment whose use is foreseen in this study
- History of allergy to any vaccine
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 |
|---|---|---|
| Kleb4V target doseTwo doses of the non-adjuvanted Kleb4V target dose will be administered intramuscularly 2 months apart | Biological | Kleb4V target dose |
| Kleb4V target dose + AS03Two doses of the adjuvanted Kleb4V target dose will be administered intramuscularly 2 months apart | Biological | Kleb4V target dose + AS03 |
| Kleb4V low doseTwo doses of the non-adjuvanted Kleb4V low dose will be administered intramuscularly 2 months apart | Biological | Kleb4V low dose |
| Kleb4V low dose + AS03Two doses of the adjuvanted Kleb4V low dose will be administered intramuscularly 2 months apart | Biological | Kleb4V low dose + AS03 |
| PlaceboTwo doses of the Placebo will be administered intramuscularly 2 months apart | Biological | Placebo (Diluent) |
Primary outcome
Safety: Occurrence, severity and relationship of solicited local and general AEs (Adverse Events)
Time frame: during 7 days following each vaccination
Occurrence, severity and relationship of solicited local and general AEs (Adverse Events)
Safety: Occurrence, severity and relationship of unsolicited AEs
Time frame: during 28 days following each vaccination
Occurrence, severity and relationship of unsolicited AEs
Safety: Occurrence, severity and relationship of medically relevant AEs, AESIs and SAEs
Time frame: through the study completion, on average of 1 year
Occurrence, severity and relationship of medically relevant AEs, AESIs (Adverse Events of Special Interest) and SAEs (Serious Adverse Events)
Immunogenicity: IgG (Immunoglobulin G) titers against the Klebsiella pneumoniae O serotypes included in the vaccine
Time frame: between baseline and 28 days after the second injection
For each active group vs. placebo: Comparison of geometric mean titers (GMTs) of serum IgG against the four K. pneumoniae O-serotypes included in Kleb4V.
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 4 Oct 2022.
- Derived from this study: PubMed 41289032Alaimo C, Karaky N, Lawrence R, Bownes E, Haffner S, Kowarik M, Goldblatt D, Martin P. Safety and Immunogenicity of a Klebsiella pneumoniae Tetravalent Bioconjugate Vaccine (Kleb4V) Administered to Healthy Adults: A First-in-Human Phase I/II Randomized and Controlled Study. J Infect Dis. 2026 Feb 18;233(2):e342-e351. doi: 10.1093/infdis/jiaf600.
- Derived from this study: PubMed 39163713Chen Z, Gou Q, Yuan Y, Zhang X, Zhao Z, Liao J, Zeng X, Jing H, Jiang S, Zhang W, Zeng H, Huang W, Zou Q, Zhang J. Vaccination with a trivalent Klebsiella pneumoniae vaccine confers protection in a murine model of pneumonia. Vaccine. 2024 Oct 3;42(23):126217. doi: 10.1016/j.vaccine.2024.126217. Epub 2024 Aug 19.
Related trials for Klebsiella Pneumoniae Infection
RecruitingPhase 4
CONTinuous Infusion Versus Intermittent Dosing of ceftaZidime/AVIbactam in Critically Ill Patients
Severe Infection
RecruitingObservational study
Epidemiology and Overtime Genomic Evolution of Klebsiella Pneumoniae and Enterobacter Cloacae Complex (ECC) in Stools of ICU's Patients
Longitudinal, Genomic Stability
Not yet recruitingObservational study
Ceftazidime-Avibactam PK/PD and Resistance in Hematology Patients
Hematologic Neoplasms, Gram-Negative Bacterial Infections
Not yet recruitingObservational study
Outer Membrane Vesicle and Ferroptosis-Related Signatures in Sepsis-Associated Acute Lung Injury Caused by Extra-Pulmonary Hypervirulent Klebsiella Pneumoniae
Sepsis, Acute Lung Injury(ALI)
RecruitingObservational study
Epidemiology of Carbapenemase-producing Bacteria in a Swiss Tertiary Care Hospital
Infections With CPB
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.
Cristina Alaimo study director
LimmaTech Biologics AG
Steffen Haffner, Dr principal investigator
Nuvisan GmbH
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Kleb4V target dose, Kleb4V target dose + AS03 and Kleb4V low dose in people with Klebsiella Pneumoniae Infection, run by LimmaTech Biologics AG at 2 sites in Germany.
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 26 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 4 Oct 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Germany. 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 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?
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?
Safety: Occurrence, severity and relationship of solicited local and general AEs (Adverse Events) (time frame: during 7 days following each vaccination). The study lists 4 primary outcomes in all. 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 NCT04959344, which also lists 2 linked publications.
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 4 Oct 2022.