Safety and Immunogenicity of a Klebsiella Pneumoniae Tetravalent Bioconjugate Vaccine (Kleb4V)

NCT04959344 | Completed Phase 1 DMC

• 1 other identifier: Kleb4V01
• Study Type: interventional
• Target: 166
• Locations: 1 country
• Sites: 2

Brief 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.

Conditions

Klebsiella Pneumoniae Infection

Outcome Measures

Primary Outcomes (4)

• 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)

  during 7 days following each vaccination

• Safety: Occurrence, severity and relationship of unsolicited AEs

  Occurrence, severity and relationship of unsolicited AEs

  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)

  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.

  between baseline and 28 days after the second injection

Study Arms (5)

Kleb4V target dose

EXPERIMENTAL

Study participants receive 2 target doses of the non-adjuvanted investigational product 2 months apart.

Biological: Kleb4V target dose

Kleb4V target dose + AS03

EXPERIMENTAL

Study participants receive 2 target doses of the adjuvanted investigational product 2 months apart.

Biological: Kleb4V target dose + AS03

Kleb4V low dose

EXPERIMENTAL

Study participants receive 2 low doses of the non-adjuvanted investigational product 2 months apart.

Biological: Kleb4V low dose

Kleb4V low dose + AS03

EXPERIMENTAL

Study participants receive 2 low doses of the adjuvanted investigational product 2 months apart.

Biological: Kleb4V low dose + AS03

Placebo (Diluent)

PLACEBO COMPARATOR

Study participants receive 2 doses of the Placebo 2 months apart.

Biological: Placebo

Interventions

Kleb4V target dose BIOLOGICAL

Two doses of the non-adjuvanted Kleb4V target dose will be administered intramuscularly 2 months apart

Kleb4V target dose

Kleb4V target dose + AS03 BIOLOGICAL

Two doses of the adjuvanted Kleb4V target dose will be administered intramuscularly 2 months apart

Kleb4V target dose + AS03

Kleb4V low dose BIOLOGICAL

Two doses of the non-adjuvanted Kleb4V low dose will be administered intramuscularly 2 months apart

Kleb4V low dose

Kleb4V low dose + AS03 BIOLOGICAL

Two doses of the adjuvanted Kleb4V low dose will be administered intramuscularly 2 months apart

Kleb4V low dose + AS03

Placebo BIOLOGICAL

Two doses of the Placebo will be administered intramuscularly 2 months apart

Placebo (Diluent)

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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)
• 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)

Sponsors & Collaborators

• LimmaTech Biologics AG: lead
• GlaxoSmithKline: collaborator

Study Sites (2)

Nuvisan GmbH, Standort Gauting, Robert-Koch-Allee 29

Gauting, 82131, Germany

Location

Nuvisan GmbH, Standort Neu-Ulm, Wegenerstrasse 13

Neu-Ulm, 89231, Germany

Location

Related Publications (2)

• 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 time in human phase I/II randomised and controlled study. J Infect Dis. 2025 Nov 25:jiaf600. doi: 10.1093/infdis/jiaf600. Online ahead of print.

  PMID: 41289032 DERIVED

• Chen 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.

  PMID: 39163713 DERIVED

Study Officials

• Cristina Alaimo

  LimmaTech Biologics AG

  STUDY DIRECTOR

• Steffen Haffner, Dr

  Nuvisan GmbH

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: observer-blind
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 25, 2021
• First Posted: July 13, 2021
• Study Start: July 5, 2021
• Primary Completion: September 26, 2022
• Study Completion: September 26, 2022
• Last Updated: October 4, 2022

Record last verified: 2022-10

Locations

DE (2)