Study to Evaluate the Ability of Sublingual MV130 to Induce the Expression of Trained Immunity in Peripheral Blood Cells

March 23, 2022 updated by: Inmunotek S.L.

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

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.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Anticipated)

48

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Description

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, - - Subjects who have been vaccinated (flu, pneumococcal or any other vaccine different from COVID-19 vaccine) within 6 months before inclusion, or who have planned to be vaccinated during the clinical trial (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

  • 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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Other
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: MV130
Suspension of 6 inactivated whole bacteria concentrates, that contains 90% of Gram positive bacteria (V104 S. pneumoniae 60%, V102 S. aureus 15%, V101 S. epidermidis 15%) and 10% of Gram negative bacteria (V113 K. pneumoniae 4%, V105 M. catarrhalis 3%, V103 H. influenzae 3%), at a concentration of 300 FTU/mL, equivalent to ~ 10^9 bacteria/mL.
Biological: MV130
Treatment administered sublingually
Placebo Comparator: Placebo
Sodium chloride 9 mg/mL and water for injection s.q. f 1 mL.
Other: Placebo
Treatment administered sublingually

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Increase ex vivo in cytokine response
Time Frame: 70 days
The primary outcome is the change ex vivo in cytokine response (TNF-alfa, IL-6 and/or IL-1beta) in PBMCs upon secondary restimulation (MV130, lipopolysaccharide [LPS], inactivated Candida albicans, Resiquimod-R848, Poly I:C and/or phytohemagglutinin [PHA]) in MV130 vaccinated subjects compared to placebo group, at days 15, 45 and/or 70, with respect to baseline.
70 days

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Changes in epigenetic markers (miRNA) in purified monocytes from PBMCs in a subgroup of MV130 vaccinated (n=12) versus placebo (n=12), at day 45 with respect to baseline.
Time Frame: 70 days
Changes in specific miRNA from total RNA associated to trained immunity (miR155, miR146 and/or miR21, etc.) by real time quantitative polymerase chain reaction (RT-qPCR) measured as expression levels.
70 days
Changes in epigenetic markers (active chromatin histone marks) in purified monocytes from PBMCs, in a subgroup of MV130 vaccinated (n=12) versus placebo (n=12), at day 45 with respect to baseline, including:
Time Frame: 70 days
Changes in active chromatin histone marks (H3K4me3 and/or H3K27me3, among others) by chromatin immunoprecipitation (ChIP) analysis, measured as relative expression.
70 days
Metabolic changes in purified monocytes from PBMCs, in a subgroup of vaccinated (n=12) versus placebo (n=12), at day 45 with respect to baseline, including:
Time Frame: 70 days

Changes in concentration of lactate production by using a colorimetric assay kit.

Changes in glucose consumption (concentration), determined by using a glucose assay kit.

Changes in mitochondrial activity, measured by using a fluorescence probe kit.
70 days
Changes in percentages of immune populations in peripheral blood
Time Frame: 70 days
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.
70 days
Change in MV130 non-specific response
Time Frame: 70 days

Change in MV130 non-specific response (T and B cells from PBMCs) in MV130 treated group compared to placebo including:

  • T cell proliferation (days 15, 45 and/or 70) by labelling T cells with carboxyfluorescein succinimidyl ester (CFSE) prior to restimulation with PHA and/or inactivated C. albicans. Also, change of cytokine production (such as IFN-gamma, IL-17 and/or IL-10) from T cells upon restimulation (LPS, inactivated Candida albicans, Resiquimod-R848, Poly I:C, viral peptides/proteins and/or PHA) (days 15, 45 and/or 70 with respect to baseline) [27].
  • Antibody production: Cross-reactive serum IgG against viral components. Different viral proteins/peptides will be tested (days 45 and 70 with respect to baseline).
70 days
MV130 specific response
Time Frame: 70 days

MV130 specific response (T and B cell responses from PBMCs) in MV130 vaccinated group compared to placebo, including:

  • T cell proliferation and cytokine production (IFN-gamma, IL-17 and/or IL-10) following restimulation with MV130 (days 15, 45 and/or 70 with respect to baseline)
  • Antibody production: MV130 specific IgG and IgA levels in serum and IgA levels in saliva (days 45 and/or 70 with respect to baseline). Individual bacteria contained in MV130 (i.e., S. pneumoniae) will be further tested for specific antibody production.
70 days
Changes in baseline oral microbiota composition in MV130 treated group
Time Frame: 70 days
Changes in baseline oral microbiota composition in MV130 treated group (days 45 and 70 with respect to baseline) compared to placebo, based o¬n the 16S rRNA sequence phylogeny
70 days
Rates of adverse events
Time Frame: 70 days
The overall rate of adverse events in both groups
70 days
Classification of the Adverse events
Time Frame: 70 days
Classification of the Adverse events during the trial
70 days
Rates of adverse reactions
Time Frame: 70 days
The overall rate of adverse reactions in both groups
70 days
Classification of the Adverse reactions
Time Frame: 70 days
Classification of the Adverse reactions during the trial
70 days
Percentage by type of adverse events
Time Frame: 70 days
Percentage by type of adverse events occurred during the trial
70 days
Percentage of subject with adverse reactions
Time Frame: 70 days
Percentage of subject experiencing adverse reactions during the trial
70 days
Timing of reaction appearance
Time Frame: 70 days
Time from the first administration to appearance of the reaction
70 days
Classification of the adverse reaction according to the place of appearance
Time Frame: 70 days
Classification of the adverse reaction in local or systemic, depending on the place of appearance
70 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Inmunotek S.L.

Investigators

  • Principal Investigator: ssramon@salud.madrid.org Sánchez-Ramón, MD and PhD, Hospital Clinico San Carlos

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Anticipated)

June 1, 2022

Primary Completion (Anticipated)

September 30, 2023

Study Completion (Anticipated)

December 31, 2023

Study Registration Dates

First Submitted

August 13, 2021

First Submitted That Met QC Criteria

January 12, 2022

First Posted (Actual)

January 26, 2022

Study Record Updates

Last Update Posted (Actual)

March 24, 2022

Last Update Submitted That Met QC Criteria

March 23, 2022

Last Verified

March 1, 2022

More Information

Terms related to this study

Keywords

Other Study ID Numbers

  • MV130-SLG-039

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Immune Response

Clinical Trials on MV130

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Taiwan

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe