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Vaccination Response Modulation With a Targeted Rapamycin Protocol Study (VON TRAPP)

11 maja 2026 zaktualizowane przez: Matthew Tunbridge, Central Adelaide Local Health Network Incorporated

Vaccination Response Modulation With a Targeted Rapamycin Protocol (VON TRAPP) Study

This study will investigate dialysis recipients' responses to important vaccines.

Research suggests that a medication commonly used by transplant recipients may improve vaccine responses. The investigators will be conducting a clinical trial to see whether a short course of low-dose Sirolimus improves the response to vaccination against respiratory syncytial virus (RSV) and influenza (flu) in patient with kidney disease over 60 years old who receive haemodialysis.

Przegląd badań

Status

Jeszcze nie rekrutacja

Warunki

Interwencja / Leczenie

Szczegółowy opis

Respiratory viruses are a significant cause of morbidity and mortality in Australia. Respiratory syncytial virus (RSV) and Influenza are major contributors to yearly respiratory virus epidemics that particularly affect older persons and persons with end-stage kidney disease.

Vaccination is available for the prevention of both RSV and Influenza, but unfortunately the conditions that confer a higher risk of morbidity and mortality with infection are also key predictors of poor responses to vaccination.

Effective vaccine responses require activation of both T and B cells to generate protective and long-lasting antibody and cellular immune responses. Immunosenescence from ageing and end-stage kidney disease, dampens antibody responses and impairs cellular immunity, rendering patients vulnerable to infection.

Previous research suggests that sirolimus(rapamycin)-based immunosuppression regimens improve vaccine immunogenicity. Sirolimus (rapamycin) is a potent inhibitor of mTORC1 which regulates memory CD8+ T cells. Targeting mTORC1 has previous been shown to improve vaccination response in humans to influenza. More recently, small studies have suggested improved responses to COVID vaccination in kidney transplant recipients switched to sirolimus (rapamycin)-based regimens.

This study will investigate a role for sirolimus (rapamycin) as a peri-vaccination immune modulation therapy. The VON TRAPP study is a phase 2a randomised clinical trial that aims to define the optimal, practical and tolerable regimen of peri-vaccination sirolimus (rapamycin) administration to positively modify vaccine responses. Haemodialysis patients over 60 years old will receive both Influenza and RSV vaccines plus either no additional treatment or a peri-vaccination regimen of sirolimus (rapamycin) to determine the most effective regimen to test further.

Typ studiów

Interwencyjne

Zapisy (Szacowany)

60

Faza

  • Faza 2

Kontakty i lokalizacje

Ta sekcja zawiera dane kontaktowe osób prowadzących badanie oraz informacje o tym, gdzie badanie jest przeprowadzane.

Kontakt w sprawie studiów

Kopia zapasowa kontaktu do badania

Lokalizacje studiów

  • Australia
    • New South Wales
      • Camperdown, New South Wales, Australia, 2050
    • Queensland
      • Woolloongabba, Queensland, Australia, 4102
    • South Australia
      • Adelaide, South Australia, Australia, 5000
        • Royal Adelaide Hospital
        • Kontakt:

Kryteria uczestnictwa

Badacze szukają osób, które pasują do określonego opisu, zwanego kryteriami kwalifikacyjnymi. Niektóre przykłady tych kryteriów to ogólny stan zdrowia danej osoby lub wcześniejsze leczenie.

Kryteria kwalifikacji

Wiek uprawniający do nauki

  • Dorosły
  • Starszy dorosły

Akceptuje zdrowych ochotników

Nie

Opis

Inclusion Criteria:

  • End-stage kidney disease requiring in-centre haemodialysis three times per week as kidney replacement therapy
  • Aged >60 years

Exclusion Criteria:

  • Aged <60 years
  • Alternative haemodialysis regimens (e.g. twice-weekly haemodialysis, second-daily home haemodialysis)
  • Recent infection (<6 months) with proven Influenza A, Influenza B, or RSV

  • Current use of immunosuppressive medications, including:

    • Oral steroid at a dose equivalent of 5 mg/day prednisolone or greater
    • Mycophenolate mofetil
    • Azathioprine
    • Calcineurin inhibitors
    • mTOR inhibitors

  • Recent use of intravenous immunosuppressive medications (<6 months), including:

    • T-cell depleting agents (e.g. anti-thymocyte globulin)
    • B-cell depleting agents (e.g. rituximab)
    • Cyclophosphamide

  • Has a history of problems with side-effects associated with sirolimus use including

    • Angioedema
    • Active/recent opportunistic infection
    • Current or prior interstitial lung disease, non-infectious pneumonitis, organising pneumonia, or pulmonary fibrosis
    • Clinically significant pleural effusion or pericardial effusion
    • Active non-healing wounds, chronic skin ulcers, or planned major surgery/procedures
    • Current malignancy or recent malignancy with high recurrence risk
    • Severe or uncontrolled hyperlipidaemia
    • History of rhabdomyolysis
    • Severe hepatic impairment

  • Ongoing use of strong CYP3A4/P-gp inhibitors or inducers including

    • Inhibitors: Ketoconazole, Voriconazole, Itraconazole, Telithromycin, Clarithromycin
    • Inducers: Rifampicin, Rifabutin
  • Unable or unwilling to provide informed consent to participate in the trial
  • Known allergy to or intolerance of sirolimus (rapamycin) or the contents of the influenza or RSV vaccine

Plan studiów

Ta sekcja zawiera szczegółowe informacje na temat planu badania, w tym sposób zaprojektowania badania i jego pomiary.

Jak projektuje się badanie?

Szczegóły projektu

  • Główny cel: Zapobieganie
  • Przydział: Randomizowane
  • Model interwencyjny: Przydział równoległy
  • Maskowanie: Brak (otwarta etykieta)

Broń i interwencje

Grupa uczestników / Arm
Interwencja / Leczenie
Aktywny komparator: Control
Influenza and RSV vaccination without additional treatment
Biologiczny: Influenza vaccine (Sequiris Fluad Quad)
All participants will receive a dose of the seasonal Influenza vaccine (Sequiris Fluad Quad)
Biologiczny: RSV vaccine (Pfizer Abrysvo)
All participants will receive a dose of the RSV vaccine (Pfizer Abrysvo)
Eksperymentalny: Pre-vaccine sirolimus group
Sirolimus 2mg orally x3/week on haemodialysis for 3 weeks. Influenza and RSV vaccination 2 weeks after completing sirolimus course.
Biologiczny: Influenza vaccine (Sequiris Fluad Quad)
All participants will receive a dose of the seasonal Influenza vaccine (Sequiris Fluad Quad)
Biologiczny: RSV vaccine (Pfizer Abrysvo)
All participants will receive a dose of the RSV vaccine (Pfizer Abrysvo)
Lek: Sirolimus (RAPAMUNE)
All treatment groups will receive 9 doses of 2mg sirolimus over a 3 week period, at varying times relative to vaccination.
Inne nazwy:
  • Rapamycyna
Eksperymentalny: Peri-vaccine sirolimus group
Sirolimus 2mg orally x3/week on haemodialysis for 3 weeks. Influenza and RSV vaccination 1 week after commencing sirolimus course.
Biologiczny: Influenza vaccine (Sequiris Fluad Quad)
All participants will receive a dose of the seasonal Influenza vaccine (Sequiris Fluad Quad)
Biologiczny: RSV vaccine (Pfizer Abrysvo)
All participants will receive a dose of the RSV vaccine (Pfizer Abrysvo)
Lek: Sirolimus (RAPAMUNE)
All treatment groups will receive 9 doses of 2mg sirolimus over a 3 week period, at varying times relative to vaccination.
Inne nazwy:
  • Rapamycyna
Eksperymentalny: Post-vaccine sirolimus group
Sirolimus 2mg orally x3/week on haemodialysis for 3 weeks. Influenza and RSV vaccination 2 weeks prior to commencing sirolimus course.
Biologiczny: Influenza vaccine (Sequiris Fluad Quad)
All participants will receive a dose of the seasonal Influenza vaccine (Sequiris Fluad Quad)
Biologiczny: RSV vaccine (Pfizer Abrysvo)
All participants will receive a dose of the RSV vaccine (Pfizer Abrysvo)
Lek: Sirolimus (RAPAMUNE)
All treatment groups will receive 9 doses of 2mg sirolimus over a 3 week period, at varying times relative to vaccination.
Inne nazwy:
  • Rapamycyna

Co mierzy badanie?

Podstawowe miary wyniku

Miara wyniku
Opis środka
Ramy czasowe
Vaccine-specific functional T cell memory
Ramy czasowe: Six weeks post vaccination
The change in functional T cell memory from baseline to six weeks post vaccine dose, measured as IFN-γ spot-forming units (SFU) by ELISpot following 18-hour stimulation of PBMCs with RSV peptides.
Six weeks post vaccination

Miary wyników drugorzędnych

Miara wyniku
Opis środka
Ramy czasowe
Cellular immune response to vaccination
Ramy czasowe: Six weeks post vaccination
RSV vaccine-specific cellular immunity, measured as 1) change in frequency of CD8+ RSV F protein-specific T cells from baseline to six weeks post vaccine dose, identified by flow cytometry as CD8+CD134+CD69+ following 24-hour stimulation with a protein-derived peptide array (AIM, Activation-Induced Marker assay); 2) Change in frequency of RSV F protein-specific polyfunctional T cells from baseline to six weeks post vaccine dose. Polyfunctional T cells are defined as CD4+ T cells that produce more than one of IFN-γ, IL-2 and TNF identified by flow cytometry intracellular cytokine staining following 24-hour stimulation with a protein-derived peptide array (ICS, Intracellular Cytokine Staining assay).
Six weeks post vaccination
Vaccine-specific humoral immune response
Ramy czasowe: Six week post vaccination
Measures of vaccine-specific humoral immunity, measured as 1) Anti-RSV F protein IgM, IgA and IgG antibody titres 6 weeks following the vaccine dose; 2) Change in haemagglutination inhibition (HAI) titre of influenza strains contained in the 2026 vaccine from baseline to six weeks post vaccination.
Six week post vaccination
Incidence of infection post-vaccination
Ramy czasowe: Twelve months post vaccination
Incidence of RSV or Influenza infection in the study cohort from 3 weeks post vaccination to 12-month follow-up
Twelve months post vaccination
Incidence of Sirolimus (Rapamycin) Treatment-Emergent Adverse Events [Safety and Tolerability]
Ramy czasowe: Six week post vaccination
Safety and tolerability of 3-week course of low-dose sirolimus (rapamycin), measured as frequency of adverse events (including serious adverse events)
Six week post vaccination
Incidence of Immunization Treatment-Emergent Adverse Events [Safety and Tolerability]
Ramy czasowe: Six weeks post vaccination
Safety and tolerability of vaccine regimen, assessed by 1. Frequency of adverse events following immunization (AEFI), including adverse events of special interest (AESI) such as recurrence of autoimmune disease
Six weeks post vaccination
Quality of life questionnaire
Ramy czasowe: Six weeks post-vaccination
Quality of life following 3-week course of low-dose sirolimus (rapamycin) and vaccination, measured with the EQ-5D-5L quality of life questionnaire. This questionnaire reports on 5 functional domains using an ordinal scale from 1 (worst) to 5 (best) to provide a combined health state score.
Six weeks post-vaccination
Circulating IL-1β analysis
Ramy czasowe: Three weeks after commencement of sirolimus (after administration of final dose of sirolimus)
Pre- and post-sirolimus circulating cytokine and chemokine analysis, measured as change in concentration of serum factor IL-1β from baseline to the end of sirolimus administration.
Three weeks after commencement of sirolimus (after administration of final dose of sirolimus)
Circulating IFN-α2 analysis
Ramy czasowe: Three weeks after commencement of sirolimus (after administration of final dose of sirolimus)
Pre- and post-sirolimus circulating cytokine and chemokine analysis, measured as change in concentration of serum factor IFN-α2 from baseline to the end of sirolimus administration.
Three weeks after commencement of sirolimus (after administration of final dose of sirolimus)
Circulating IFN-γ analysis
Ramy czasowe: Three weeks after commencement of sirolimus (after administration of final dose of sirolimus)
Pre- and post-sirolimus circulating cytokine and chemokine analysis, measured as change in concentration of serum factors IFN-γ from baseline to the end of sirolimus administration.
Three weeks after commencement of sirolimus (after administration of final dose of sirolimus)
Circulating TNF-α analysis
Ramy czasowe: Three weeks after commencement of sirolimus (after administration of final dose of sirolimus)
Pre- and post-sirolimus circulating cytokine and chemokine analysis, measured as change in concentration of serum factors TNF-α from baseline to the end of sirolimus administration.
Three weeks after commencement of sirolimus (after administration of final dose of sirolimus)
Circulating MCP-1 analysis
Ramy czasowe: Three weeks after commencement of sirolimus (after administration of final dose of sirolimus)
Pre- and post-sirolimus circulating cytokine and chemokine analysis, measured as change in concentration of serum factors MCP-1 from baseline to the end of sirolimus administration.
Three weeks after commencement of sirolimus (after administration of final dose of sirolimus)
Circulating IL-6 analysis
Ramy czasowe: Three weeks after commencement of sirolimus (after administration of final dose of sirolimus)
Pre- and post-sirolimus circulating cytokine and chemokine analysis, measured as change in concentration of serum factor IL-6 from baseline to the end of sirolimus administration.
Three weeks after commencement of sirolimus (after administration of final dose of sirolimus)
Circulating CXCL8 (IL-8)
Ramy czasowe: Three weeks after commencement of sirolimus (after administration of final dose of sirolimus)
Pre- and post-sirolimus circulating cytokine and chemokine analysis, measured as change in concentration of serum factor CXCL8 (IL-8) from baseline to the end of sirolimus administration.
Three weeks after commencement of sirolimus (after administration of final dose of sirolimus)
Circulating IL-10 analysis
Ramy czasowe: Three weeks after commencement of sirolimus (after administration of final dose of sirolimus)
Pre- and post-sirolimus circulating cytokine and chemokine analysis, measured as change in concentration of serum factor IL-10 from baseline to the end of sirolimus administration.
Three weeks after commencement of sirolimus (after administration of final dose of sirolimus)
Circulating IL-12p70 analysis
Ramy czasowe: Three weeks after commencement of sirolimus (after administration of final dose of sirolimus)
Pre- and post-sirolimus circulating cytokine and chemokine analysis, measured as change in concentration of serum factor IL-12p70 from baseline to the end of sirolimus administration.
Three weeks after commencement of sirolimus (after administration of final dose of sirolimus)
Circulating IL-17A analysis
Ramy czasowe: Three weeks after commencement of sirolimus (after administration of final dose of sirolimus)
Pre- and post-sirolimus circulating cytokine and chemokine analysis, measured as change in concentration of serum factors IL-17A from baseline to the end of sirolimus administration.
Three weeks after commencement of sirolimus (after administration of final dose of sirolimus)
Circulating IL-18 analysis
Ramy czasowe: Three weeks after commencement of sirolimus (after administration of final dose of sirolimus)
Pre- and post-sirolimus circulating cytokine and chemokine analysis, measured as change in concentration of serum factors IL-18 from baseline to the end of sirolimus administration.
Three weeks after commencement of sirolimus (after administration of final dose of sirolimus)
Circulating IL-23 analysis
Ramy czasowe: Three weeks after commencement of sirolimus (after administration of final dose of sirolimus)
Pre- and post-sirolimus circulating cytokine and chemokine analysis, measured as change in concentration of serum factors IL-23 from baseline to the end of sirolimus administration.
Three weeks after commencement of sirolimus (after administration of final dose of sirolimus)
Circulating IL-33 analysis
Ramy czasowe: Three weeks after commencement of sirolimus (after administration of final dose of sirolimus)
Pre- and post-sirolimus circulating cytokine and chemokine analysis, measured as change in concentration of serum factors IL-33 from baseline to the end of sirolimus administration.
Three weeks after commencement of sirolimus (after administration of final dose of sirolimus)
Circulating CRP analysis
Ramy czasowe: Three weeks after commencement of sirolimus (after administration of final dose of sirolimus)
Pre- and post-sirolimus circulating cytokine and chemokine analysis, measured as change in concentration of serum factors CRP from baseline to the end of sirolimus administration.
Three weeks after commencement of sirolimus (after administration of final dose of sirolimus)

Współpracownicy i badacze

Tutaj znajdziesz osoby i organizacje zaangażowane w to badanie.

Sponsor

Central Adelaide Local Health Network Incorporated

Daty zapisu na studia

Daty te śledzą postęp w przesyłaniu rekordów badań i podsumowań wyników do ClinicalTrials.gov. Zapisy badań i zgłoszone wyniki są przeglądane przez National Library of Medicine (NLM), aby upewnić się, że spełniają określone standardy kontroli jakości, zanim zostaną opublikowane na publicznej stronie internetowej.

Główne daty studiów

Rozpoczęcie studiów (Szacowany)

1 maja 2026

Zakończenie podstawowe (Szacowany)

1 lipca 2026

Ukończenie studiów (Szacowany)

1 lipca 2026

Daty rejestracji na studia

Pierwszy przesłany

6 maja 2026

Pierwszy przesłany, który spełnia kryteria kontroli jakości

11 maja 2026

Pierwszy wysłany (Rzeczywisty)

14 maja 2026

Aktualizacje rekordów badań

Ostatnia wysłana aktualizacja (Rzeczywisty)

14 maja 2026

Ostatnia przesłana aktualizacja, która spełniała kryteria kontroli jakości

11 maja 2026

Ostatnia weryfikacja

1 maja 2026

Więcej informacji

Terminy związane z tym badaniem

Słowa kluczowe

Dodatkowe istotne warunki MeSH

Inne numery identyfikacyjne badania

  • 2025/HRE00483

Plan dla danych uczestnika indywidualnego (IPD)

Planujesz udostępniać dane poszczególnych uczestników (IPD)?

TAK

Opis planu IPD

Anonymized patient-level data created for the study will be available in a persistent repository upon publication. Data will be uploaded to figshare.com.

Ramy czasowe udostępniania IPD

Anonymized IPD will be made available in a persistent repository from the date of publication of trial findings.

Kryteria dostępu do udostępniania IPD

Anonymized IPD will be publicly accessible by download from the persistent repository.

Informacje o lekach i urządzeniach, dokumenty badawcze

Bada produkt leczniczy regulowany przez amerykańską FDA

Nie

Bada produkt urządzenia regulowany przez amerykańską FDA

Nie

produkt wyprodukowany i wyeksportowany z USA

Nie

Te informacje zostały pobrane bezpośrednio ze strony internetowej clinicaltrials.gov bez żadnych zmian. Jeśli chcesz zmienić, usunąć lub zaktualizować dane swojego badania, skontaktuj się z register@clinicaltrials.gov. Gdy tylko zmiana zostanie wprowadzona na stronie clinicaltrials.gov, zostanie ona automatycznie zaktualizowana również na naszej stronie internetowej .

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