Clinical trial NCT04665791: 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
Overall status: COMPLETED
Phase: NA
Conditions: Meningitis, Meningococcal
Keywords: Meningitis
Controlled human infection
Healthy volunteer
Neisseria lactamica
Lyophilization
Lead sponsor: Center for Vaccine Development - Mali
Sponsor class: OTHER
Collaborators: name: University of Southampton
name: University of Maryland
name: University College, London
name: University of Oxford
name: Public Health England
First posted: 2020-12-14
Enrollment: 55
Sex: ALL
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: A prospective dose-ranging human challenge study. Nasal inoculation with reconstituted, previously lyophilised Neisseria lactamica with dose escalation.
Primary purpose: BASIC_SCIENCE

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.

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

Primary outcomes:
measure: Establish the impact of nasal inoculation of healthy Malian volunteers with reconstituted lyophilised Neisseria lactamica by assessing nasopharyngeal colonisation with Neisseria species
timeFrame: 6 months
measure: Establish the effect of the nasal inoculation of healthy Malian volunteers with reconstituted lyophilised Neisseria lactamica by collecting information about symptoms
timeFrame: 6 months
measure: Analyse the haemoglobin of healthy Malian volunteers inoculated with reconstituted lyophilised Neisseria lactamica
timeFrame: 3 months
measure: Analyse the white cell count of healthy Malian volunteers inoculated with reconstituted lyophilised Neisseria lactamica
timeFrame: 3 months
measure: Analyse the platelet count of healthy Malian volunteers inoculated with reconstituted lyophilised Neisseria lactamica
timeFrame: 3 months
measure: Analyse the biochemistry blood results (ALT) of healthy Malian volunteers inoculated with reconstituted lyophilised Neisseria lactamica
timeFrame: 3 months
measure: Analyse the biochemistry blood results (Creatinine) of healthy Malian volunteers inoculated with reconstituted lyophilised Neisseria lactamica
timeFrame: 3 months
Secondary outcomes:
measure: The dose of reconstituted lyophilised Neisseria lactamica required for nasopharyngeal colonisation in at least 70% of inoculees
timeFrame: 6 months
measure: To measure Neisseria lactamica specific immunity following nasal inoculation with reconstituted lyophilised Neisseria lactamica
timeFrame: 1 year
Other outcomes:
Locations:
city: Bamako
country: Mali
facility: CVD Mali
Study officials:
affiliation: University of Southampton
name: Robert C Read, MD FRCP
role: PRINCIPAL_INVESTIGATOR
affiliation: Center for Vaccine Development - Mali
name: Samba Sow, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Maryland
name: Milagritos Tapia, MD
role: PRINCIPAL_INVESTIGATOR
References: