Vaccination Response Modulation With a Targeted Rapamycin Protocol Study
For patients and families
In plain language
An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.
- What is being studied
- The protocol lists: Sirolimus (RAPAMUNE), Influenza vaccine (Sequiris Fluad Quad), RSV vaccine (Pfizer Abrysvo).
- Who it may be relevant to
- Registry conditions: Vaccine Immune Response, Haemodialysis Patients, Older Adults. Basic parameters: from 60 years · All.
- What needs checking
- Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
- Where it takes place
- Australia
- Next step
- Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →
Unsure about the terms? Read our patient guide →
Official title
Vaccination Response Modulation With a Targeted Rapamycin Protocol (VON TRAPP) Study
Overview
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.
Detailed description
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.
Interventions
- Drug Sirolimus (RAPAMUNE)
All treatment groups will receive 9 doses of 2mg sirolimus over a 3 week period, at varying times relative to vaccination. - Biological Influenza vaccine (Sequiris Fluad Quad)
All participants will receive a dose of the seasonal Influenza vaccine (Sequiris Fluad Quad) - Biological RSV vaccine (Pfizer Abrysvo)
All participants will receive a dose of the RSV vaccine (Pfizer Abrysvo)
Primary outcome measures
- Vaccine-specific functional T cell memory [Time frame: Six weeks post vaccination]
Secondary outcome measures (12)
- Cellular immune response to vaccination [Time frame: Six weeks post vaccination]
- Vaccine-specific humoral immune response [Time frame: Six week post vaccination]
- Incidence of infection post-vaccination [Time frame: Twelve months post vaccination]
- Incidence of Sirolimus (Rapamycin) Treatment-Emergent Adverse Events [Safety and Tolerability] [Time frame: Six week post vaccination]
- Incidence of Immunization Treatment-Emergent Adverse Events [Safety and Tolerability] [Time frame: Six weeks post vaccination]
- Quality of life questionnaire [Time frame: Six weeks post-vaccination]
- Circulating IL-1β analysis [Time frame: Three weeks after commencement of sirolimus (after administration of final dose of sirolimus)]
- Circulating IFN-α2 analysis [Time frame: Three weeks after commencement of sirolimus (after administration of final dose of sirolimus)]
- Circulating IFN-γ analysis [Time frame: Three weeks after commencement of sirolimus (after administration of final dose of sirolimus)]
- Circulating TNF-α analysis [Time frame: Three weeks after commencement of sirolimus (after administration of final dose of sirolimus)]
- Circulating MCP-1 analysis [Time frame: Three weeks after commencement of sirolimus (after administration of final dose of sirolimus)]
- Circulating IL-6 analysis [Time frame: Three weeks after commencement of sirolimus (after administration of final dose of sirolimus)]
Eligibility criteria
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
Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.
Healthy volunteers: No
Study design
- Allocation
- Randomized
- Model
- Parallel assignment
- Masking
- Open label
- Primary purpose
- Prevention
Study locations
Australia · 3 centers
- Royal Prince Alfred Hospital — Camperdown
- Princess Alexandra Hospital — Woolloongabba
- Royal Adelaide Hospital — Adelaide
Identifiers
NCT: NCT07587801 · 2025/HRE00483