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A Controlled Study to Assess Safety, Colonisation and Immunogenicity of Reconstituted Lyophilised Neisseria Lactamica (Lac5-Nasal)

Primary Purpose

Meningitis, Bacterial

Status
Unknown status
Phase
Not Applicable
Locations
United Kingdom
Study Type
Interventional
Intervention
Lyophilised Neisseria lactamica
Sponsored by
University of Southampton
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Meningitis, Bacterial focused on measuring meningitis, healthy volunteer

Eligibility Criteria

18 Years - 45 Years (Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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

Sites / Locations

  • NIHR Southampton Clinical Research FacilityRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Challenge

Arm Description

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.

Outcomes

Primary Outcome Measures

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,
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
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
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
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

Secondary Outcome Measures

The dose of lyophilised Neisseria lactamica required for nasopharyngeal colonisation in 80% of inoculees.
The dose will be confirmed by nasal swabs and nasal washes taken from participants and analysed for bacteria by CFU counts. The desired dose will be confirmed when 80% of participants are colonised.

Full Information

First Posted
September 27, 2019
Last Updated
October 21, 2019
Sponsor
University of Southampton
Collaborators
University Hospital Southampton NHS Foundation Trust
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1. Study Identification

Unique Protocol Identification Number
NCT04135053
Brief Title
A Controlled Study to Assess Safety, Colonisation and Immunogenicity of Reconstituted Lyophilised Neisseria Lactamica
Acronym
Lac5-Nasal
Official Title
A Human Controlled Infection Study to Assess Safety, Colonisation and Immunogenicity Following Nasal Inoculation With Reconstituted Lyophilised Wild Type Neisseria Lactamica
Study Type
Interventional

2. Study Status

Record Verification Date
October 2019
Overall Recruitment Status
Unknown status
Study Start Date
February 1, 2019 (Actual)
Primary Completion Date
February 1, 2020 (Anticipated)
Study Completion Date
December 31, 2021 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Southampton
Collaborators
University Hospital Southampton NHS Foundation Trust

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes

5. Study Description

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.
Detailed Description
In this pilot research, the research team will develop and validate a modification of the methodology previously used in another UK-based human challenge experiments. The research to be conducted in this study will inform the study team whether intranasal inoculation of reconstituted lyophilised Nlac (hereafter, lyoNlac), can result in immunising colonisation of participants and the optimal dose to achieve this. Previous challenges have been conducted using frozen stocks of Nlac but this is relatively unsatisfactory because of instability of frozen stocks, and will not be practical in Mali. The facility to reconstitute dry powdered lyoNlac into water and inoculate as a nose drop will greatly simplify the experimental method. However, it is not known whether lyoNlac can be inoculated directly into volunteers and induce successful colonisation. In summary this is a pilot study of the safety, efficacy and immunogenicity of the intranasal inoculation of healthy human volunteers with lyoNlac. This study will determine the efficacy of lyoNlac as an agent for inducing nasopharyngeal colonisation with this organism, which is an important methodological development for ease of administration of Nlac in experimental human challenge studies. The study team will aim to determine the dose of inoculum required to induce colonisation in 80% of volunteers (the Standard Inoculum or SI). This SI will be used in future studies aiming to optimise duration of colonisation and immunogenicity induced by lyoNlac.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Meningitis, Bacterial
Keywords
meningitis, healthy volunteer

7. Study Design

Primary Purpose
Prevention
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Model Description
A prospective dose ranging human challenge study. Nasal inoculation with reconstituted, previously lyophilised Neisseria lactamica with dose escalation / de-escalation.
Masking
None (Open Label)
Allocation
N/A
Enrollment
35 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Challenge
Arm Type
Experimental
Arm Description
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.
Intervention Type
Biological
Intervention Name(s)
Lyophilised Neisseria lactamica
Intervention Description
Previously lyophilised Neisseria lactamica will be reconstituted and intranasally given to participants
Primary Outcome Measure Information:
Title
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.
Description
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,
Time Frame
1 year
Title
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.
Description
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
Time Frame
1 Year
Title
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.
Description
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
Time Frame
1 Year
Title
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.
Description
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
Time Frame
1 Year
Title
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.
Description
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
Time Frame
1 Year
Secondary Outcome Measure Information:
Title
The dose of lyophilised Neisseria lactamica required for nasopharyngeal colonisation in 80% of inoculees.
Description
The dose will be confirmed by nasal swabs and nasal washes taken from participants and analysed for bacteria by CFU counts. The desired dose will be confirmed when 80% of participants are colonised.
Time Frame
1 year

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
45 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: 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 Exclusion Criteria: 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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Diane Gbesemete
Phone
+44(0) 2381 204989
Email
diane.gbesemete@uhs.nhs.uk
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Robert C Read
Organizational Affiliation
University of Southampton
Official's Role
Principal Investigator
Facility Information:
Facility Name
NIHR Southampton Clinical Research Facility
City
Southampton
Country
United Kingdom
Individual Site Status
Recruiting
Facility Contact:
Email
UHS.recruitmentCRF@nhs.net

12. IPD Sharing Statement

Learn more about this trial

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

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