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A Human Controlled Infection Study With Neisseria Lactamica in Malian Adults

Primary Purpose

Meningitis, Meningococcal

Status

Unknown status

Phase

Not Applicable

Locations

Mali

Study Type

Interventional

Intervention

Intranasal inoculation with Neisseria lactamica

About this trial

This is an interventional basic science trial for Meningitis, Meningococcal focused on measuring Meningitis, Controlled human infection, Healthy volunteer, Neisseria lactamica, Lyophilization

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 residing outside the demographic surveillance area
Able and willing (in the investigator's opinion) to understand and comply with all study requirements including availability for all study follow up visits
Provide written informed consent to participate in the trial
For females only, all the following:
willingness to practice continuous effective contraception at least until the Day 28 visit is complete
negative urine pregnancy test on the screening day
negative urine pregnancy test on inoculation day

Exclusion Criteria:

Eligibility Minimum Age: 18 Years Maximum Age: 45 Years Sex: All Gender Based: No Accepts Healthy Volunteers: Yes

Criteria: Inclusion Criteria:

Healthy adults aged 18 to 45 years inclusive on the day of enrolment residing outside the demographic surveillance area
Able and willing (in the investigator's opinion) to understand and comply with all study requirements including availability for all study follow up visits
Provide written informed consent to participate in the trial
For females only, all the following:
willingness to practice continuous effective contraception at least until the Day 28 visit is complete
negative urine pregnancy test on the screening day
negative urine pregnancy test on inoculation day

Exclusion Criteria:

N. lactamica detected on throat swab taken at the screening visit
Individuals who have an ongoing acute illness 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
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 (including oral steroids) 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 to soya.
Any clinically significant abnormal finding on clinical examination or screening investigations
History of any surgery to the nose or throat in the previous 3 months
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
Occupational, household or intimate contact with immunosuppressed persons
Positive pregnancy test or lactation

Sites / Locations

CVD MaliRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Challenge

Arm Description

Challenge participants will be inoculated intranasally with reconstituted, previously lyophilised Neisseria lactamica (LyoNlac). The initial dose will be 10^5 colony forming units and will be escalated to a maximum of 10^7 colony forming units to find the dose which successfully colonises at least 70% of volunteers.

Outcomes

Primary Outcome Measures

Establish the impact of nasal inoculation of healthy Malian volunteers with reconstituted lyophilised Neisseria lactamica by assessing nasopharyngeal colonisation with Neisseria species

Throat swabs will be taken at standardised visits and analysed for nasopharyngeal colonisation with Neisseria species. Standard tests include culture and polymerase chain reaction (PCR)

Establish the effect of the nasal inoculation of healthy Malian volunteers with reconstituted lyophilised Neisseria lactamica by collecting information about symptoms

Information about symptoms will be collected at standardised visits. Any symptoms will be recorded and assessed by a study doctor. If deemed necessary by the study doctor further tests will be requested.

Analyse the haemoglobin of healthy Malian volunteers inoculated with reconstituted lyophilised Neisseria lactamica

Blood samples will be taken at specified time points and compared to those collected at baseline. Any change in results will be recorded and, if deemed necessary by the medical team, further tests will be requested. Standard tests - haemoglobin - g/dL

Analyse the white cell count of healthy Malian volunteers inoculated with reconstituted lyophilised Neisseria lactamica

Analyse the platelet count of healthy Malian volunteers inoculated with reconstituted lyophilised Neisseria lactamica

Analyse the biochemistry blood results (ALT) of healthy Malian volunteers inoculated with reconstituted lyophilised Neisseria lactamica

Analyse the biochemistry blood results (Creatinine) of healthy Malian volunteers inoculated with reconstituted lyophilised Neisseria lactamica

Secondary Outcome Measures

The dose of reconstituted lyophilised Neisseria lactamica required for nasopharyngeal colonisation in at least 70% of inoculees

The dose will be confirmed by throat swabs taken from participants and analysed for bacteria by culture and polymerase chain reaction. The desired dose will be confirmed when at least 70%o of inoculees are colonised

To measure Neisseria lactamica specific immunity following nasal inoculation with reconstituted lyophilised Neisseria lactamica

Blood samples will be collected at standardised visits and antibody levels (mg/dL) will be measured to assess if those colonised with Neisseria lactamica show an increase in antibody levels in comparison to baseline

Full Information

NCT ID

NCT04665791

First Posted

December 7, 2020

Last Updated

March 1, 2021

Sponsor

Center for Vaccine Development - Mali

Collaborators

University of Southampton, University of Maryland, College Park, University College, London, University of Oxford, Public Health England

1. Study Identification

Unique Protocol Identification Number

NCT04665791

Brief Title

A Human Controlled Infection Study With Neisseria Lactamica in Malian Adults

Official Title

A Human Controlled Infection Study to Assess Colonisation and Immunogenicity Following Nasal Inoculation of Malian Adults With Reconstituted Lyophilised Wild Type Neisseria Lactamica (Lactamica Etape 1)

Study Type

Interventional

2. Study Status

Record Verification Date

March 2021

Overall Recruitment Status

Unknown status

Study Start Date

March 2, 2021 (Actual)

Primary Completion Date

January 2022 (Anticipated)

Study Completion Date

January 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Center for Vaccine Development - Mali

Collaborators

University of Southampton, University of Maryland, College Park, University College, London, University of Oxford, Public Health England

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

This study is part of a series of projects to improve protection against meningitis. Previously, researchers have given nose drops containing N. lactamica to over 400 volunteers and shown that many of them become colonised with N. lactamica without causing any illness or disease. This has previously been shown to prevent people from becoming colonised with N. meningitidis which can cause meningitis. This study aims to give nose drops containing N. lactamica to healthy adults in Mali, to see if they become safely colonised. 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 study team will use a methodology of nasal inoculation with reconstituted lyophilised N. lactamica (hereafter LyoNlac) developed in a previous, UK-based, human challenge study. This methodology and will be developed further and validated in healthy Malian adults. A dose-ranging strategy will be used, starting with the dose identified as the standard inoculum in healthy adults in the UK, which was the dose required to induce colonisation in approximately 80% of volunteers. The dose will be escalated to a dose able to induce a similar level of colonisation in Malian adults. This study will inform the study team whether intranasal inoculation of reconstituted lyophilised Nlac (hereafter, lyoNlac), can result in immunising colonisation of adult Malian volunteers and the optimal dose to achieve this. This dose and methodology will then be used in future studies looking at the duration and immunogenicity of colonisation induced by LyoNlac in Mali.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Meningitis, Meningococcal

Keywords

Meningitis, Controlled human infection, Healthy volunteer, Neisseria lactamica, Lyophilization

7. Study Design

Primary Purpose

Basic Science

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.

Masking

None (Open Label)

Allocation

N/A

Enrollment

25 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Challenge

Arm Type

Experimental

Arm Description

Intervention Type

Biological

Intervention Name(s)

Intranasal inoculation with Neisseria lactamica

Intervention Description

Lyophilised Neisseria lactamica will be reconstituted and administered to participants intranasally.

Primary Outcome Measure Information:

Title

Establish the impact of nasal inoculation of healthy Malian volunteers with reconstituted lyophilised Neisseria lactamica by assessing nasopharyngeal colonisation with Neisseria species

Description

Throat swabs will be taken at standardised visits and analysed for nasopharyngeal colonisation with Neisseria species. Standard tests include culture and polymerase chain reaction (PCR)

Time Frame

6 months

Title

Establish the effect of the nasal inoculation of healthy Malian volunteers with reconstituted lyophilised Neisseria lactamica by collecting information about symptoms

Description

Time Frame

6 months

Title

Analyse the haemoglobin of healthy Malian volunteers inoculated with reconstituted lyophilised Neisseria lactamica

Description

Time Frame

3 months

Title

Analyse the white cell count of healthy Malian volunteers inoculated with reconstituted lyophilised Neisseria lactamica

Description

Time Frame

3 months

Title

Analyse the platelet count of healthy Malian volunteers inoculated with reconstituted lyophilised Neisseria lactamica

Description

Time Frame

3 months

Title

Analyse the biochemistry blood results (ALT) of healthy Malian volunteers inoculated with reconstituted lyophilised Neisseria lactamica

Description

Time Frame

3 months

Title

Analyse the biochemistry blood results (Creatinine) of healthy Malian volunteers inoculated with reconstituted lyophilised Neisseria lactamica

Description

Time Frame

3 months

Secondary Outcome Measure Information:

Title

The dose of reconstituted lyophilised Neisseria lactamica required for nasopharyngeal colonisation in at least 70% of inoculees

Description

Time Frame

6 months

Title

To measure Neisseria lactamica specific immunity following nasal inoculation with reconstituted lyophilised Neisseria lactamica

Description

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

Eligibility Criteria

Inclusion Criteria: Healthy adults aged 18 to 45 years inclusive on the day of enrolment residing outside the demographic surveillance area Able and willing (in the investigator's opinion) to understand and comply with all study requirements including availability for all study follow up visits Provide written informed consent to participate in the trial For females only, all the following: willingness to practice continuous effective contraception at least until the Day 28 visit is complete negative urine pregnancy test on the screening day negative urine pregnancy test on inoculation day Exclusion Criteria: Eligibility Minimum Age: 18 Years Maximum Age: 45 Years Sex: All Gender Based: No Accepts Healthy Volunteers: Yes Criteria: Inclusion Criteria: Healthy adults aged 18 to 45 years inclusive on the day of enrolment residing outside the demographic surveillance area Able and willing (in the investigator's opinion) to understand and comply with all study requirements including availability for all study follow up visits Provide written informed consent to participate in the trial For females only, all the following: willingness to practice continuous effective contraception at least until the Day 28 visit is complete negative urine pregnancy test on the screening day negative urine pregnancy test on inoculation day Exclusion Criteria: N. lactamica detected on throat swab taken at the screening visit Individuals who have an ongoing acute illness 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 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 (including oral steroids) 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 to soya. Any clinically significant abnormal finding on clinical examination or screening investigations History of any surgery to the nose or throat in the previous 3 months 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 Occupational, household or intimate contact with immunosuppressed persons Positive pregnancy test or lactation

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Diane F Gbesemete, BM MRCPCH

Phone

+44 2381204956

d.gbesemete@soton.ac.uk

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Robert C Read, MD FRCP

Organizational Affiliation

University of Southampton

Official's Role

Principal Investigator

First Name & Middle Initial & Last Name & Degree

Samba Sow, MD

Organizational Affiliation

Center for Vaccine Development - Mali

Official's Role

Principal Investigator

First Name & Middle Initial & Last Name & Degree

Milagritos Tapia, MD

Organizational Affiliation

University of Maryland, College Park

Official's Role

Principal Investigator

Facility Information:

Facility Name

CVD Mali

City

Bamako

Country

Mali

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Diane F Gbesemete, BM

Phone

02381204956

d.gbesemete@soton.ac.uk

12. IPD Sharing Statement

Plan to Share IPD

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A Human Controlled Infection Study With Neisseria Lactamica in Malian Adults

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