A Controlled Study to Assess Safety, Colonisation and Immunogenicity of Reconstituted Lyophilised Neisseria Lactamica

NCT04135053 | Unknown DMC

• 1 other identifier: Lac5-Nasal
• Study Type: interventional
• Target: 35
• Locations: 1 country
• Sites: 1

Brief Summary

This study is part of a series of projects to develop and test new vaccines for meningitis. Previously researchers have given nose drops containing N. lactamica to over 350 volunteers, and shown that many of them (35-60%) can become colonised with N. lactamica and become resistant to becoming colonised with N.meningitidis without causing any illness or disease. In the future the study team would like to find out how N.lactamica helps children resist N.meningitidis, and develop new vaccines that exploit that mechanism.

Conditions

Meningitis, Bacterial

Keywords

meningitis; healthy volunteer

Outcome Measures

Primary Outcomes (5)

• Via the hospital Pathology service, analyse the haematology blood results of healthy volunteers inoculated with reconstituted lyophilised wild type Neisseria lactamica, taken at specified time points.

  Blood samples will be taken at standardised visits. Results will be compared to those results collected from baseline and pre-inoculation visits. Any change in results will be recorded and, if deemed required by the medical team, further tests requested. Standard tests haematology- haemoglobin - g/L,

  1 year

• Via the hospital Pathology service, analyse the White Cell Count of healthy volunteers inoculated with reconstituted lyophilised wild type Neisseria lactamica, taken at specified time points.

  Blood samples will be taken at standardised visits. Results will be compared to those results collected from baseline and pre-inoculation visits. Any change in results will be recorded and, if deemed required by the medical team, further tests requested. Standard tests include haematology - White Cell Count - x10\^9/L

  1 Year

• Via the hospital Pathology service, analyse the Platelet Count of healthy volunteers inoculated with reconstituted lyophilised wild type Neisseria lactamica, taken at specified time points.

  Blood samples will be taken at standardised visits. Results will be compared to those results collected from baseline and pre-inoculation visits. Any change in results will be recorded and, if deemed required by the medical team, further tests requested. Standard tests include haematology - Platelet Count - x10\^9/L

  1 Year

• Via the hospital Pathology service, analyse the Biochemistry results of healthy volunteers inoculated with reconstituted lyophilised wild type Neisseria lactamica, taken at specified time points.

  Blood samples will be taken at standardised visits. Results will be compared to those results collected from baseline and pre-inoculation visits. Any change in results will be recorded and, if deemed required by the medical team, further tests requested. Standard tests include Biochemistry - Sodium - mmol/L

  1 Year

• Via the hospital Pathology service, analyse the CRP results of healthy volunteers inoculated with reconstituted lyophilised wild type Neisseria lactamica, taken at specified time points.

  Blood samples will be taken at standardised visits. Results will be compared to those results collected from baseline and pre-inoculation visits. Any change in results will be recorded and, if deemed required by the medical team, further tests requested. Standard tests include Biochemistry - C-reactive protein - mg/L

  1 Year

Secondary Outcomes (1)

• The dose of lyophilised Neisseria lactamica required for nasopharyngeal colonisation in 80% of inoculees.

  1 year

Study Arms (1)

Challenge

EXPERIMENTAL

Challenge participants will inoculated intranasallly with reconstituted lyophilised Neisseria lactamica (lyoNlac). The initial dose will be 10\^5 colony-forming units (CFU) and will be escalated or de-escalated by 1/2 - 1 log depending upon the proportion of volunteers colonies with viable N. lactamica.

Biological: Lyophilised Neisseria lactamica

Interventions

Lyophilised Neisseria lactamica BIOLOGICAL

Previously lyophilised Neisseria lactamica will be reconstituted and intranasally given to participants

Challenge

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy adults aged 18 to 45 years inclusive on the day of enrolment
• Fully conversant in the English language
• Able and willing (in the investigator's opinion) to comply with all study requirements
• Provide written informed consent to participate in the trial
• For females only, willingness to practice continuous effective contraception (see below) during the study and a negative pregnancy test on the day(s) of screening and inoculation
• TOPS registration completed and no conflict found

You may not qualify if:

• Current active smokers defined as having smoked a cigarette or cigar in the last four weeks
• N. lactamica or N. meningitidis detected on throat swab or nasal wash taken at screening
• Individuals who have a current infection at the time of inoculation
• Individuals who have been involved in other clinical trials involving receipt of an investigational product over the last 12 weeks or if there is planned use of an investigational product during the study period
• Individuals who have previously been involved in clinical trials investigating meningococcal vaccines or experimental challenge with N. lactamica
• Use of systemic antibiotics within the period 30 days prior to the challenge
• Any confirmed or suspected immunosuppressive or immune-deficient state, including HIV infection; asplenia; recurrent, severe infections and chronic (more than 14 days) immunosuppressant medication within the past 6 months (topical steroids are allowed)
• Use of immunoglobulins or blood products within 3 months prior to enrolment.
• History of allergic disease or reactions likely to be exacerbated by any component of the inoculum, specifically soya.
• Contraindications to the use of ciprofloxacin, specifically a history of epilepsy, prolonged QT interval, hypersensitivity to quinolones or a history of tendon disorders related to quinolone use
• Any clinically significant abnormal finding on clinical examination or screening investigations
• Any other significant disease, disorder, or finding which may significantly increase the risk to the volunteer because of participation in the study, affect the ability of the volunteer to participate in the study or impair interpretation of the study data, for example recent surgery to the nasopharynx
• Occupational, household or intimate contact with immunosuppressed persons
• Pregnancy or lactation

Sponsors & Collaborators

• University of Southampton: lead
• University Hospital Southampton NHS Foundation Trust: collaborator

Study Sites (1)

NIHR Southampton Clinical Research Facility

Southampton, United Kingdom

RECRUITING

Related Publications (1)

• Gbesemete DF, Haidara F, Laver JR, Ibrahim M, MacLennan J, Dale AP, Gorringe AR, Traore Y, Diallo F, Badji H, Traore A, Onwuchekwa U, Jones E, Webb C, Guy J, Theodosiou AA, Faust SN, Sow SO, Heyderman RS, Tapia MD, Read RC. Controlled Human Infection of Healthy Adults With Lyophilized Neisseria lactamica Induces Asymptomatic, Immunogenic Nasopharyngeal Carriage in the United Kingdom and Mali. Open Forum Infect Dis. 2026 Jan 7;13(1):ofaf809. doi: 10.1093/ofid/ofaf809. eCollection 2026 Jan.

  PMID: 41574175 DERIVED

MeSH Terms

Conditions

Meningitis, Bacterial; Meningitis

Condition Hierarchy (Ancestors)

Central Nervous System Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Central Nervous System Infections; Central Nervous System Diseases; Nervous System Diseases; Neuroinflammatory Diseases

Study Officials

• Robert C Read

  University of Southampton

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Diane Gbesemete

CONTACT

+44(0) 2381 204989; diane.gbesemete@uhs.nhs.uk

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: A prospective dose ranging human challenge study. Nasal inoculation with reconstituted, previously lyophilised Neisseria lactamica with dose escalation / de-escalation.

Study Record Dates

• First Submitted: September 27, 2019
• First Posted: October 22, 2019
• Study Start: February 1, 2019
• Primary Completion: February 1, 2020
• Study Completion: December 31, 2021
• Last Updated: October 22, 2019

Record last verified: 2019-10

Locations

GB (1)