Eosinophilic Granulomatosis With PolyangiitisEPI-EGPANCT06231498
The Epigenomic Signature of Eosinophilic Granulomatosis With Polyangiitis
An observational study of Eosinophilic Granulomatosis With Polyangiitis, run by Meyer Children's Hospital IRCCS.
Trial summary
This is a case-control observational study on blood samples. The primary goal of this study is to identify the epigenetic marks that can distinguish patients suffering from Eosinophilic Granulomatosis with Polyangiitis (EGPA) from healthy individuals. Read more about this study
- Who is it for?
- Ages 18 to 99 years
- Conditions the study is for
- Eosinophilic Granulomatosis With Polyangiitis
- How many people
- 300 participants
- Where
- No sites listed yet
- Study dates
- Apr 2024to Dec 2025
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 99 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: The study will include 300 adult (>18yo) patients with Eosinophilic Granulomatosis with Polyangiitis (EGPA). All patients will be recruited at Meyer Children's Hospital and Careggi University Hospital, which are referral centres for EGPA and have a large cohort of prevalent cases under long-term follow-up. They will represent the cases for the case-control epigenome-wide association study. Patients are expected to be untreated or under glucocorticoids at the time of sampling. A blood sample will be drawn for each participant. Among this cohort, 50 patients will be identified that will undergo treatment with Mepolizumab, and they will form the sub-cohort in which epigenetic predictors of the response to Mepolizumab treatment (predictive epigenomic study) will be searched for.
Who may be able to join
- Patients over 18 years of age who meet the 1990 American College of Rheumatology classification criteria for EGPA or the criteria proposed in the MIRRA trial, or the 2022 American College of Rheumatology/European Alliance of Associations for Rheumatology classification criteria;
- Written informed consent from all the study participants.
Who cannot join
- Patients with inadequate or unavailable data regarding response to treatment at months 6 and 12 after Mepolizumab initiation will be included in the case-control Epigenome-Wide Association Study (EWAS) but not in the predictive epigenomic study;
- Patients with childhood-onset EGPA;
- Patients who are pregnant or breast-feeding.
Trial locations and contacts
No sites are listed yet.
About this study
Official title: Disease Susceptibility and Response to IL5 Blockade in Patients With Eosinophilic Granulomatosis With Polyangiitis (EGPA): an Epigenome-wide Association Study Integrated With Transcriptomic and Proteomic Analyses
This is a case-control observational study on blood samples. The primary goal of this study is to identify the epigenetic marks that can distinguish patients suffering from Eosinophilic Granulomatosis with Polyangiitis (EGPA) from healthy individuals. The secondary goal is to identify epigenetic or transcriptional marks that can predict if a patient with EGPA will benefit from therapy with Mepolizumab. This study is observational, meaning there will be no alterations of patients' routine clinical care. A blood sample will be drawn for each patient. If the patient will undergo treatment with Mepolizumab (based on routine clinical care), then the blood sample will be drawn before Mepolizumab initiation. The blood samples will be used for genome-wide DNA methylation profiling and for transcriptomic profiling. Healthy individuals as controls for the association study will not be recruited. In fact, the epigenetic and transcriptomic data obtained from EGPA patient blood will be compared against already available genome-wide DNA methylation and transcriptomic profiles of the blood of healthy individuals from previous studies. A total of 300 patients with EGPA will be recruited for the study. The first part of the study, corresponding to the primary goal, will involve all of the 300 patients. The second part of the study, corresponding to the secondary goal, will involve a study population subset consisting of 50 patients.
Read the detailed description
Background and Rationale. Eosinophilic Granulomatosis with Polyangiitis (EGPA) is a rare multisystem immune-mediated disease classified both among Anti Neutrophil Cytoplasmic Antibody (ANCA)-associated vasculitis and among hypereosinophilic disorders. Current scientific knowledge describes EGPA as a complex or multifactorial nature of the disease, i.e. the disease is triggered by a combination of inherited genetic variants and environmental factors. The term "epigenetics" refers to heritable alterations in gene expression which do not correspond to a variation in the underlying DNA sequence. In the context of various autoimmune diseases similar to EGPA and in the context of asthma (a condition that almost all EGPA patients suffer from), several studies have highlighted that epigenetics plays a fundamental role in the pathogenesis/pathophysiology and that in particular it can potentially represent the mechanism by which environmental exposures interact with genetics to cause the disease. Therefore, studying epigenetics (and namely DNA methylation as the most studied epigenetic mechanism) in EGPA could lead to an in-depth knowledge of the pathology and in particular to the identification of epigenetic markers, useful in diagnosis, or in monitoring disease activity, or in predicting response to pharmacological treatment.
Objectives. The primary objective is the identification of loci whose methylation level is associated with the pathology (i.e. epigenetic markers of the disease). The secondary objectives are: identification of loci whose methylation level correlates with the response to treatment with the drug Mepolizumab in patients affected by the disease (i.e. epigenetic markers predictive of response to Mepolizumab); identification of genes whose transcription level is related to the disease and of proteins whose plasma concentration is related to the disease (in this way, we expect to evaluate the effects of epigenetic variation on gene/protein expression and to identify the corresponding biological pathways); identification of epigenetic predictors of disease outcomes, e.g. remission, relapse, survival; identification of epigenetic markers of the main disease subphenotypes, i.e. the ANCA+ and ANCA- subsets.
Study Design. Observational case-control study on biological samples. The study is divided into two different parts: The first part is a genome-wide DNA methylation case-control association study. The genome-wide methylation profile derived from blood samples from 300 patients will be compared to the methylation profile in the blood of healthy individuals. The second part is a predictive study, aiming at assessing whether epigenetics can be used to predict the response to Mepolizumab. This part of the study will cover a study population subset, consisting of 50 patients who will undergo treatment with Mepolizumab (as part of their clinical routine) and whose blood sample will be drawn before starting Mepolizumab therapy. Not only the genome-wide methylation profile will be obtained from the blood (like all the other patients included in the study), but also the transcriptomic profile. These profiles will be analyzed to search for loci whose level of methylation and/or expression correlate with the response to treatment with Mepolizumab.
- Keywords
- Epigenome, DNA Methylation, Eosinophilic Granulomatosis with Polyangiitis, EGPA
- Medical subject headings
- Churg-Strauss Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Overall Cohort | The study will include 300 adult (>18yo) patients with Eosinophilic Granulomatosis with Polyangiitis (EGPA). All patients will be recruited at Meyer Children's Hospital and Careggi University Hospital, which are referral centers for EGPA and have a large cohort of prevalent cases under long-term follow-up. They will represent the cases for the case-control epigenome-wide association study. Patients are expected to be untreated or under glucocorticoids at the time of sampling. A blood sample will be drawn for each participant. Among this cohort, 50 patients will be identified that will undergo treatment with Mepolizumab, and they will form the sub-cohort in which we will search for epigenetic predictors of the response to Mepolizumab treatment (predictive epigenomic study). These 50 patients will also be analyzed with regard to the transcriptomic and proteomic profile. Written informed consent from all participants and approval from the local ethical committees will be obtained. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Epigenome-Wide Association Study
The primary objective of the study is the identification of loci whose methylation level is associated with the pathology (i.e. epigenetic markers of the disease). This means that there is not any outcome that will be measured with regard to the primary objective.
Measured: Through study completion, an average of 1 year
Mepolizumab Therapy Response
The main secondary objective of the study is the identification of loci whose methylation level correlates with the response to treatment with the Mepolizumab in patients with EGPA (i.e. epigenetic predictors of response to Mepolizumab). To this end, the response to treatment with Mepolizumab is the outcome that will be measured. Complete response to treatment will be defined as no disease activity (Birmingham Vasculitis Activity Score = 0) and a prednisolone or prednisone dose (or equivalent) of ≤4.0 mg/day, as defined by the MIRRA trial. Partial response to treatment will be defined as no disease activity and a prednisone dose (or equivalent) of >4.0 mg/day.
Measured: 6 months and 12 months after Mepolizumab therapy initiation
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Jan 2024
- Study startApr 2024 (estimated)
- Primary completionSep 2025 (estimated)
- Study completionDec 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Eosinophilic Granulomatosis With PolyangiitisStudies of the same condition, open and under way.
- More trials run by Meyer Children's Hospital IRCCSThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case-control
- Time perspective
- Prospective
- Enrolment
- 300 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Meyer Children's Hospital IRCCS
- Sponsor type
- University, hospital or other
- Collaborators
- Careggi Hospital, University of Florence
- Responsible party
- Principal investigator, Augusto Vaglio, Meyer Children's Hospital IRCCS
- Investigators
- Augusto Vaglio, MD, PhD, Principal investigator, Meyer Children's Hospital IRCCS
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06231498
- Sponsor's protocol ID
- EPI-EGPA
- Acronym
- EPI-EGPA
- Status last verified
- Feb 2024
- First submitted
- 14 Nov 2023
- Last updated
- 23 Feb 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: Individual participant data will not be shared with researchers other than the study investigators
Study at a glance
From the registry record, last updated by the sponsor on 23 Feb 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Disease Susceptibility and Response to IL5 Blockade in Patients With Eosinophilic Granulomatosis With Polyangiitis (EGPA): an Epigenome-wide Association Study Integrated With Transcriptomic and Proteomic Analyses
- ClinicalTrials.gov ID
- NCT06231498
- Acronym / sponsor ID
- EPI-EGPA / EPI-EGPA
- Keywords
- Epigenome, DNA Methylation, Eosinophilic Granulomatosis with Polyangiitis, EGPA
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 300 participants (estimated)
- Lead sponsor
- Meyer Children's Hospital IRCCSUniversity, hospital or other
- Collaborators
- Careggi Hospital, University of Florence
- Study start
- Apr 2024 (estimated)
- Primary completion
- Sep 2025 (estimated)
- Study completion
- Dec 2025 (estimated)
- First posted
- 30 Jan 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a case-control observational study on blood samples. The primary goal of this study is to identify the epigenetic marks that can distinguish patients suffering from Eosinophilic Granulomatosis with Polyangiitis (EGPA) from healthy individuals. The secondary goal is to identify epigenetic or transcriptional marks that can predict if a patient with EGPA will benefit from therapy with Mepolizumab. This study is observational, meaning there will be no alterations of patients' routine clinical care. A blood sample will be drawn for each patient. If the patient will undergo treatment with Mepolizumab (based on routine clinical care), then the blood sample will be drawn before Mepolizumab initiation. The blood samples will be used for genome-wide DNA methylation profiling and for transcriptomic profiling. Healthy individuals as controls for the association study will not be recruited. In fact, the epigenetic and transcriptomic data obtained from EGPA patient blood will be compared against already available genome-wide DNA methylation and transcriptomic profiles of the blood of healthy individuals from previous studies. A total of 300 patients with EGPA will be recruited for the study. The first part of the study, corresponding to the primary goal, will involve all of the 300 patients. The second part of the study, corresponding to the secondary goal, will involve a study population subset consisting of 50 patients.
Detailed description
Background and Rationale. Eosinophilic Granulomatosis with Polyangiitis (EGPA) is a rare multisystem immune-mediated disease classified both among Anti Neutrophil Cytoplasmic Antibody (ANCA)-associated vasculitis and among hypereosinophilic disorders. Current scientific knowledge describes EGPA as a complex or multifactorial nature of the disease, i.e. the disease is triggered by a combination of inherited genetic variants and environmental factors. The term "epigenetics" refers to heritable alterations in gene expression which do not correspond to a variation in the underlying DNA sequence. In the context of various autoimmune diseases similar to EGPA and in the context of asthma (a condition that almost all EGPA patients suffer from), several studies have highlighted that epigenetics plays a fundamental role in the pathogenesis/pathophysiology and that in particular it can potentially represent the mechanism by which environmental exposures interact with genetics to cause the disease. Therefore, studying epigenetics (and namely DNA methylation as the most studied epigenetic mechanism) in EGPA could lead to an in-depth knowledge of the pathology and in particular to the identification of epigenetic markers, useful in diagnosis, or in monitoring disease activity, or in predicting response to pharmacological treatment.
Objectives. The primary objective is the identification of loci whose methylation level is associated with the pathology (i.e. epigenetic markers of the disease). The secondary objectives are: identification of loci whose methylation level correlates with the response to treatment with the drug Mepolizumab in patients affected by the disease (i.e. epigenetic markers predictive of response to Mepolizumab); identification of genes whose transcription level is related to the disease and of proteins whose plasma concentration is related to the disease (in this way, we expect to evaluate the effects of epigenetic variation on gene/protein expression and to identify the corresponding biological pathways); identification of epigenetic predictors of disease outcomes, e.g. remission, relapse, survival; identification of epigenetic markers of the main disease subphenotypes, i.e. the ANCA+ and ANCA- subsets.
Study Design. Observational case-control study on biological samples. The study is divided into two different parts: The first part is a genome-wide DNA methylation case-control association study. The genome-wide methylation profile derived from blood samples from 300 patients will be compared to the methylation profile in the blood of healthy individuals. The second part is a predictive study, aiming at assessing whether epigenetics can be used to predict the response to Mepolizumab. This part of the study will cover a study population subset, consisting of 50 patients who will undergo treatment with Mepolizumab (as part of their clinical routine) and whose blood sample will be drawn before starting Mepolizumab therapy. Not only the genome-wide methylation profile will be obtained from the blood (like all the other patients included in the study), but also the transcriptomic profile. These profiles will be analyzed to search for loci whose level of methylation and/or expression correlate with the response to treatment with Mepolizumab.
Study design
- Observational model
- Case-control
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Overall Cohort | – | –The study will include 300 adult (>18yo) patients with Eosinophilic Granulomatosis with Polyangiitis (EGPA). All patients will be recruited at Meyer Children's Hospital and Careggi University Hospital, which are referral centers for EGPA and have a large cohort of prevalent cases under long-term follow-up. They will represent the cases for the case-control epigenome-wide association study. Patients are expected to be untreated or under glucocorticoids at the time of sampling. A blood sample will be drawn for each participant. Among this cohort, 50 patients will be identified that will undergo treatment with Mepolizumab, and they will form the sub-cohort in which we will search for epigenetic predictors of the response to Mepolizumab treatment (predictive epigenomic study). These 50 patients will also be analyzed with regard to the transcriptomic and proteomic profile. Written informed consent from all participants and approval from the local ethical committees will be obtained. |
Who may qualify
- Ages
- 18 to 99 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- The study will include 300 adult (>18yo) patients with Eosinophilic Granulomatosis with Polyangiitis (EGPA). All patients will be recruited at Meyer Children's Hospital and Careggi University Hospital, which are referral centres for EGPA and have a large cohort of prevalent cases under long-term follow-up. They will represent the cases for the case-control epigenome-wide association study. Patients are expected to be untreated or under glucocorticoids at the time of sampling. A blood sample will be drawn for each participant. Among this cohort, 50 patients will be identified that will undergo treatment with Mepolizumab, and they will form the sub-cohort in which epigenetic predictors of the response to Mepolizumab treatment (predictive epigenomic study) will be searched for.
Key inclusion criteria (2 listed)
- Patients over 18 years of age who meet the 1990 American College of Rheumatology classification criteria for EGPA or the criteria proposed in the MIRRA trial, or the 2022 American College of Rheumatology/European Alliance of Associations for Rheumatology classification criteria;
- Written informed consent from all the study participants.
Key exclusion criteria (3 listed)
- Patients with inadequate or unavailable data regarding response to treatment at months 6 and 12 after Mepolizumab initiation will be included in the case-control Epigenome-Wide Association Study (EWAS) but not in the predictive epigenomic study;
- Patients with childhood-onset EGPA;
- Patients who are pregnant or breast-feeding.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Epigenome-Wide Association Study
Time frame: Through study completion, an average of 1 year
The primary objective of the study is the identification of loci whose methylation level is associated with the pathology (i.e. epigenetic markers of the disease). This means that there is not any outcome that will be measured with regard to the primary objective.
Mepolizumab Therapy Response
Time frame: 6 months and 12 months after Mepolizumab therapy initiation
The main secondary objective of the study is the identification of loci whose methylation level correlates with the response to treatment with the Mepolizumab in patients with EGPA (i.e. epigenetic predictors of response to Mepolizumab). To this end, the response to treatment with Mepolizumab is the outcome that will be measured. Complete response to treatment will be defined as no disease activity (Birmingham Vasculitis Activity Score = 0) and a prednisolone or prednisone dose (or equivalent) of ≤4.0 mg/day, as defined by the MIRRA trial. Partial response to treatment will be defined as no disease activity and a prednisone dose (or equivalent) of >4.0 mg/day.
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Feb 2024.
- Individual participant dataSharing planned: No. Individual participant data will not be shared with researchers other than the study investigators
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Augusto Vaglio, MD, PhD principal investigator
Meyer Children's Hospital IRCCS
Questions about this trial
What is this clinical trial studying?
An observational study of Eosinophilic Granulomatosis With Polyangiitis, run by Meyer Children's Hospital IRCCS.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 23 Feb 2024. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Augusto Vaglio, MD, PhD (+39 0555662905, augusto.vaglio@meyer.it), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Epigenome-Wide Association Study (time frame: Through study completion, an average of 1 year). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Feb 2024.