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

NCT05208060 | Unknown Phase 1

• 1 other identifier: MV130-SLG-039
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 1

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.

Conditions

Immune Response

Keywords

Trained immunity; Innate immune system; MV130; Sublingual vaccine; Trained immunity-based vaccines

Outcome Measures

Primary Outcomes (1)

• Increase ex vivo in cytokine response

  The primary outcome is the increase 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 Outcomes (13)

• 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.

  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 (T and B cells from PBMCs) in MV130 treated group compared to placebo.

  70 days

• MV130 specific response (T and B cells responses form PBMCs) in MV130 vaccinated group compared to placebo.

  70 days

• 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.

  70 days

Study Arms (2)

MV130

EXPERIMENTAL

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

Placebo

PLACEBO COMPARATOR

Sodium chloride 9 mg/mL and water for injection s.q. f 1 mL.

Other: Placebo

Interventions

MV130 BIOLOGICAL

Treatment administered sublingually

MV130

Placebo OTHER

Treatment administered sublingually

Placebo

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.
• \*: 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.

Sponsors & Collaborators

• Inmunotek S.L.: lead

Study Sites (1)

Hospital Clínico San Carlos

Madrid, 28040, Spain

RECRUITING

Related Publications (11)

• Netea MG, Dominguez-Andres J, Barreiro LB, Chavakis T, Divangahi M, Fuchs E, Joosten LAB, van der Meer JWM, Mhlanga MM, Mulder WJM, Riksen NP, Schlitzer A, Schultze JL, Stabell Benn C, Sun JC, Xavier RJ, Latz E. Defining trained immunity and its role in health and disease. Nat Rev Immunol. 2020 Jun;20(6):375-388. doi: 10.1038/s41577-020-0285-6. Epub 2020 Mar 4.

  PMID: 32132681 BACKGROUND

• Sanchez-Ramon S, Conejero L, Netea MG, Sancho D, Palomares O, Subiza JL. Trained Immunity-Based Vaccines: A New Paradigm for the Development of Broad-Spectrum Anti-infectious Formulations. Front Immunol. 2018 Dec 17;9:2936. doi: 10.3389/fimmu.2018.02936. eCollection 2018.

  PMID: 30619296 BACKGROUND

• Guevara-Hoyer K, Saz-Leal P, Diez-Rivero CM, Ochoa-Grullon J, Fernandez-Arquero M, Perez de Diego R, Sanchez-Ramon S. Trained Immunity Based-Vaccines as a Prophylactic Strategy in Common Variable Immunodeficiency. A Proof of Concept Study. Biomedicines. 2020 Jul 9;8(7):203. doi: 10.3390/biomedicines8070203.

  PMID: 32660100 BACKGROUND

• Alecsandru D, Valor L, Sanchez-Ramon S, Gil J, Carbone J, Navarro J, Rodriguez J, Rodriguez-Sainz C, Fernandez-Cruz E. Sublingual therapeutic immunization with a polyvalent bacterial preparation in patients with recurrent respiratory infections: immunomodulatory effect on antigen-specific memory CD4+ T cells and impact on clinical outcome. Clin Exp Immunol. 2011 Apr;164(1):100-7. doi: 10.1111/j.1365-2249.2011.04320.x.

  PMID: 21391984 BACKGROUND

• Garcia Gonzalez LA, Arrutia Diez F. Mucosal bacterial immunotherapy with MV130 highly reduces the need of tonsillectomy in adults with recurrent tonsillitis. Hum Vaccin Immunother. 2019;15(9):2150-2153. doi: 10.1080/21645515.2019.1581537. Epub 2019 Apr 17.

  PMID: 30779677 BACKGROUND

• Nieto A, Mazon A, Nieto M, Calderon R, Calaforra S, Selva B, Uixera S, Palao MJ, Brandi P, Conejero L, Saz-Leal P, Fernandez-Perez C, Sancho D, Subiza JL, Casanovas M. Bacterial Mucosal Immunotherapy with MV130 Prevents Recurrent Wheezing in Children: A Randomized, Double-Blind, Placebo-controlled Clinical Trial. Am J Respir Crit Care Med. 2021 Aug 15;204(4):462-472. doi: 10.1164/rccm.202003-0520OC.

  PMID: 33705665 BACKGROUND

• Cirauqui C, Benito-Villalvilla C, Sanchez-Ramon S, Sirvent S, Diez-Rivero CM, Conejero L, Brandi P, Hernandez-Cillero L, Ochoa JL, Perez-Villamil B, Sancho D, Subiza JL, Palomares O. Human dendritic cells activated with MV130 induce Th1, Th17 and IL-10 responses via RIPK2 and MyD88 signalling pathways. Eur J Immunol. 2018 Jan;48(1):180-193. doi: 10.1002/eji.201747024. Epub 2017 Sep 14.

  PMID: 28799230 BACKGROUND

• Vazquez A, Fernandez-Sevilla LM, Jimenez E, Perez-Cabrera D, Yanez R, Subiza JL, Varas A, Valencia J, Vicente A. Involvement of Mesenchymal Stem Cells in Oral Mucosal Bacterial Immunotherapy. Front Immunol. 2020 Nov 19;11:567391. doi: 10.3389/fimmu.2020.567391. eCollection 2020.

  PMID: 33329530 BACKGROUND

• Del Fresno C, Garcia-Arriaza J, Martinez-Cano S, Heras-Murillo I, Jarit-Cabanillas A, Amores-Iniesta J, Brandi P, Dunphy G, Suay-Corredera C, Pricolo MR, Vicente N, Lopez-Perrote A, Cabezudo S, Gonzalez-Corpas A, Llorca O, Alegre-Cebollada J, Garaigorta U, Gastaminza P, Esteban M, Sancho D. The Bacterial Mucosal Immunotherapy MV130 Protects Against SARS-CoV-2 Infection and Improves COVID-19 Vaccines Immunogenicity. Front Immunol. 2021 Nov 18;12:748103. doi: 10.3389/fimmu.2021.748103. eCollection 2021.

  PMID: 34867974 BACKGROUND

• Ochoa-Grullon J, Benavente Cuesta C, Gonzalez Fernandez A, Cordero Torres G, Perez Lopez C, Pena Cortijo A, Conejero Hall L, Mateo Morales M, Rodriguez de la Pena A, Diez-Rivero CM, Rodriguez de Frias E, Guevara-Hoyer K, Fernandez-Arquero M, Sanchez-Ramon S. Trained Immunity-Based Vaccine in B Cell Hematological Malignancies With Recurrent Infections: A New Therapeutic Approach. Front Immunol. 2021 Feb 12;11:611566. doi: 10.3389/fimmu.2020.611566. eCollection 2020.

  PMID: 33679698 BACKGROUND

• Molero-Abraham M, Sanchez-Trincado JL, Gomez-Perosanz M, Torres-Gomez A, Subiza JL, Lafuente EM, Reche PA. Human Oral Epithelial Cells Impair Bacteria-Mediated Maturation of Dendritic Cells and Render T Cells Unresponsive to Stimulation. Front Immunol. 2019 Jun 28;10:1434. doi: 10.3389/fimmu.2019.01434. eCollection 2019.

  PMID: 31316504 BACKGROUND

Study Officials

• Silvia Sánchez-Ramón, MD and PhD

  Hospital Clinico San Carlos

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Miguel Casanovas Verges, MD, PhD

CONTACT

664277223; mcasanovas@inmunotek.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: Randomization will be done in a 1:1 ratio in blocks of 6, through a random list. It will be impossible for investigators to know to which group a subject will be assigned before being included in the study.
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 13, 2021
• First Posted: January 26, 2022
• Study Start: September 1, 2023
• Primary Completion: January 30, 2025
• Study Completion: December 31, 2025
• Last Updated: September 19, 2024

Record last verified: 2023-09

Locations

ES (1)