Klebsiella pneumoniae (K. pneumoniae), a gram negative Enterobacteriaceae, is an opportunistic pathogen leading to hospital- and community-acquired infections (urinary tract infections, pneumonia and septicaemia). An effective vaccine could potentially reduce the use of last resort antibiotics by limiting the spread of resistant strains and even prevent infections with pan-resistant isolates, which are not treatable with antibiotics anymore. MedDRA version: 20.0 Level: LLT Classification code
Conditions
Interventions
Product Name: Kleb4V
Pharmaceutical Form: Injection
INN or Proposed INN: Kleb4V
CAS Number: 68583-24-4
Other descriptive name: Bioconjugate
Concentration unit: µg microgram(s)
Concentration type: rang
Sponsors
LimmaTech Biologics AG
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. 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, and without fever may be enrolled at the discretion of the investigator) 2. 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) 3. Signed written informed consent obtained from the subject 4. For Step 1 Groups 1 and 2 only: Female or male between 18-40 years (inclusive) of age at the time of the first vaccination 5. 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 6. 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. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 116 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 50
Exclusion criteria
Exclusion criteria: 1. 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 judgment on a case-by-case basis to assess safety risks under this criterion 2. Any clinically significant deviation from the normal range in biochemistry or hematology blood tests in the opinion of the investigator 3. Clinically significant abnormalities on physical examination 4. 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 5. History of allergy to any vaccine 6. Clinical conditions representing a contraindication to intramuscular vaccination and blood draws (e.g. coagulation disorder) 7. 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 8. Known or suspected impairment of immunological function, documented Human Immunodeficiency Virus (HIV) infection, asplenia/splenectomy, or history of autoimmune disease or lymphoprolipherative disorder 9. Positive blood test for HBsAg, HCV, HIV-1/2 10. Positive test for SARS-CoV-2 11. 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. 12. Administration of antineoplastic and immune-modulating agents or chemotherapy within 90 days prior to informed consent 13. 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 vaccine if on the market) is allowed outside of +/- 7 days from each vaccination 14. 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) 15. Body Mass Index (BMI) 30 16. History of any chronic or progressive disease that according to judgment of the investigator could interfere with the study outcomes or pose a threat to the participant's health 17. 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 perio
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of this Phase I/II study is to obtain first-in-human safety and immunogenicity data following administration of Kleb4V to 55-70 years old adults and identify the preferred formulation of Kleb4V.;Secondary Objective: Secondary objectives: - Evaluation of the vaccine induced antibodies at several timepoints following administration of Kleb4V. - Evaluation of seroconversion (at least 4 fold increase vs. baseline) at 1 month following each vaccination, at 14 days after 1st injection (in Step 2), at V6 pre-2nd dose, and at the end of the study. - Evaluation of the immunological profile through immunological functional assays confirmed with at least one Klebsiella serotype. Exploratory objectives: - Evaluation of the cross-reactivity of the Kleb4V-induced immune-response against selected Klebsiella serotypes not included in Kleb4V vaccine formulations - Assessment of microbial colonization, including change in Klebsiella spp colonization status at time of first vaccination and at last visit.;Primary end point(s): Safety and Immunogenicity ;Timepoint(s) of evaluation of this end point: Safety - Occurrence, severity and relationship of solicited local and general AEs during 7 days following each vaccination (i.e. day of vaccination and the 6 subsequent days) - Occurrence, severity and relationship of unsolicited AEs during 28 days following each vaccination (i.e. day of injection and the 27 subsequent days) - Occurrence, severity and relationship of medically relevant AEs, AESIs and SAEs throughout the study duration. Immunogenicity - Evaluation of geometric mean titers (GMTs) for serum IgG against the four K. pneumoniae O-serotypes included in Kleb4V, between baseline and post- vaccination samples collected at V8 (i.e. 28 days after the second injection). | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): -Evaluation of geometric mean titers (GMTs) for serum IgG against the four K. pneumoniae O-serotypes included in Kleb4V on samples collected at V4, V5, V6 and at the last study visit (V9) vs. baseline. -Evaluation of fold-increases between baseline and post- vaccination samples of serum IgG against the four K. pneumoniae O-serotypes included in Kleb4V, collected at V4, V5, V6, V8, and V9. -Percentage of subjects achieving at least a four-fold rise in anti-O antigens K. pneumoniae antibody concentration at V5 and V8 (i.e. 28 days after each injection), at V4 (i.e. 14 days after 1st injection (as applicable in Step 2)), at V6 pre-2nd dose and at V9 at the end of the study, compared to baseline. -Evaluation of antibody functionality (i.e. by opsonic titer, avidity or serum bactericidal assay) in post vs. pre-vaccination samples and between arms vs placebo.;Timepoint(s) of evaluation of this end point: -Evaluation of geometric mean titers (GMTs) for serum IgG against the four K. pneumoniae O-serotypes included in Kleb4V on samples collected at V4, V5, V6 and V9 vs. baseline. -Evaluation of fold-increases between baseline and post- vaccination samples of serum IgG against the four K. pneumoniae O-serotypes included in Kleb4V, collected at V4, V5, V6, V8, and V9. -Percentage of subjects achieving at least a four-fold rise in anti-O antigens K. pneumoniae antibody concentration at V5 and V8, at V4, at V6 pre-2nd dose and at V9, compared to baseline. -Evaluation of antibody functionality (i.e. by opsonic titer, avidity or serum bactericidal assay) in post vs. pre-vaccination samples and between arms vs placebo. | — |
Countries
Germany
Contacts
Public ContactStudieninformation
Nuvisan GmbH
Outcome results
None listed