Clinical trial NCT05208060: Study to Evaluate the Ability of Sublingual MV130 to Induce the Expression of Trained Immunity in Peripheral Blood Cells
Official title: A Phase I/II Randomized, Prospective, Double-blind, Placebo-controlled, Single-center Study to Evaluate the Ability of Sublingual MV130 to Induce the Expression of Trained Immunity in Peripheral Blood Cells
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Immune Response
Keywords: Trained immunity
Innate immune system
MV130
Sublingual vaccine
Trained immunity-based vaccines
Lead sponsor: Inmunotek S.L.
Sponsor class: INDUSTRY
First posted: 2022-01-26
Enrollment: 48
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

Brief summary: A mechanistic clinical trial with the aim to evaluate whether MV130 can induce the expression of a particular immune response (trained immunity) in peripheral blood cells. Therefore, the investigators are not evaluating efficacy in any disease or medical condition but rather assessing the immunological effect in immunogenicity of MV130 in healthy volunteers.

Detailed description: Bacillus Calmette-Guérin (BCG) has been postulated as a strategy to prevent transmission and reduce the incidence of infectious diseases due to its ability to induce trained immunity. However, it is not recommended to vaccinate with live-attenuated vaccines, such as BCG, to certain vulnerable populations including immunocompromised patients. This issue can be overcome with inactivated preparations that mediate trained immunity such as MV130. The safety of MV130 in pilot studies in patients with immunodeficiency or solid organ recipients, has been highlighted in recent studies.

Based on the principles of trained immunity, it has recently been suggested that this concept can be further exploited in a next generation of anti-infectious vaccines: Trained immunity-based vaccines (TIbV). Thus, these vaccines may confer a broad protection far beyond to the nominal antigens they contain.

Eligibility criteria: Inclusion Criteria:

* Subjects that have provided written informed consent.
* Healthy males and females 18 to 65 years, both included, at the time of enrolment.
* Subjects who are able to provide cooperation and comply with dosing regimen.
* Women of childbearing age (from menarche) should submit a urine pregnancy test with a negative result at the time of enrolment in the trial.

Exclusion Criteria:

* Simultaneous participation in another clinical trial.
* Females who are pregnant or breast-feeding, or potential pregnant or breast-feeding females.
* Subjects who are allergic to any of the components included in MV130.
* Subjects with any concomitant disease or treatment that, according to the investigator criteria, may affect the development of this study, such as immunodeficiencies, malignancies involving bone marrow or lymphoid systems, medical treatment affecting the immune system (including corticosteroids, immunosuppressants, biological agents,...), human immunodeficiency virus, severe allergies, diabetes, hypertension, psychological disorders, etc.
* Subjects who have been vaccinated within 12 months before inclusion (flu or any other vaccine different from COVID-19 vaccine), or who have planned to be vaccinated during the clinical study (excluding the COVID-19 vaccine).
* Subjects who have had an infection that included fever and/or diarrhoea within 3 months before inclusion.
* Subjects under metformin treatment during the last month before inclusion in the clinical study or during the clinical trial\*.
* Subjects under statins treatment during the last month before inclusion in the clinical trial or during\*.

  \*: these drugs interfere with metabolic pathways involved in trained immunity induction.
* Subjects who are allergic to any of the components included in the flu vaccine.

Primary outcomes:
measure: Increase ex vivo in cytokine response
timeFrame: 70 days
Secondary outcomes:
measure: Epigenetic and metabolic changes in purified monocytes from PBMCs, in a subgroup of MV130 vaccinated (n=12) versus placebo (n=12), at day 45 with respect to baseline.
timeFrame: 70 days
measure: Changes in percentages of immune populations in peripheral blood including T and B cells, NK cells and subsets of monocytes, in MV130 group compared to placebo at days 15, 45 and/or 70, with respect to baseline.
timeFrame: 70 days
measure: Change in MV130 non-specific response (T and B cells from PBMCs) in MV130 treated group compared to placebo.
timeFrame: 70 days
measure: MV130 specific response (T and B cells responses form PBMCs) in MV130 vaccinated group compared to placebo.
timeFrame: 70 days
measure: Change in baseline oral microbiota composition in MV130 treated group (days 45 and 70 with respect to baseline) compared to placebo, based on the 16S rRNA sequence phylogeny.
timeFrame: 70 days
measure: Rates of adverse events
timeFrame: 70 days
measure: Classification of the Adverse events
timeFrame: 70 days
measure: Rates of adverse reactions
timeFrame: 70 days
measure: Classification of the Adverse reactions
timeFrame: 70 days
measure: Percentage by type of adverse events
timeFrame: 70 days
measure: Percentage of subject with adverse reactions
timeFrame: 70 days
measure: Timing of reaction appearance
timeFrame: 70 days
measure: Classification of the adverse reaction according to the place of appearance
timeFrame: 70 days
Other outcomes:
Locations:
city: Madrid
country: Spain
facility: Hospital Clínico San Carlos
Study officials:
affiliation: Hospital Clinico San Carlos
name: Silvia Sánchez-Ramón, MD and PhD
role: PRINCIPAL_INVESTIGATOR
References:
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