Liver DiseaseNCT01437969
Pharmacogenomics Study on IL28B Genetic Variants in Italian Patients With HCV Infection naïve to Treatment.
An observational study of Liver Disease, run by Casa Sollievo della Sofferenza IRCCS at 1 site in Italy.
Trial summary
More than 1.5 millions individuals are infected with HCV in Italy. They are at risk to develop related morbidity and mortality from cirrhosis and hepatocellular carcinoma, unless the evolution of their disease is halted by treatment-induced HCV RNA clearance. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Liver Disease
- What is being tested?
- genotyping and/or sequencing
- How many people
- 500 participants
- Where
- 1 siteItaly
- Study dates
- Sep 2011to Sep 2022
- 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 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: HCV infected patients previously untreated
Who may be able to join
- Patients with chronic HCV infection irrespective of HCV genotype
Who cannot join
- HCV infected patients previously treated with antiviral drugs; co-infected Patients with HIV or Hepatitis B virus (HBsAg positive)
Trial locations and contacts
1 site in 1 country.
Italy1 site
IRCCS "Casa Sollievo della Sofferenza"
San Giovanni Rotondo, Foggia, 71013
About this study
Official title: Pharmacogenomics Study on IL28B Genetic Variants in Italian Patients With HCV Chronic Infection naïve to Antiviral Treatment.
More than 1.5 millions individuals are infected with HCV in Italy. They are at risk to develop related morbidity and mortality from cirrhosis and hepatocellular carcinoma, unless the evolution of their disease is halted by treatment-induced HCV RNA clearance. Indeed, it is well recognized that a curative antiviral treatment, leading to HCV RNA undetectability 24 weeks after the end of therapy, may prevent the occurrence of complications of HCV chronic liver disease.
Several pre-treatment host and viral factors have been associated with the outcome of pegylated Interferon and Ribavirin treatment. These predictors are relevant as the ability to identify patients with the highest likelihood of achieving HCV RNA clearance may increase the number of patients who agree to be treated and who maintain their adherence to treatment.
Read more
Several pre-treatment predictors as HCV genotype, HCV viral load, age, gender, body mass index, stage of fibrosis and race are very well recognized and have been used for many years during the treatment decision-making process. Based on studies of viral kinetics, HCV RNA undetectable at week 4 on treatment has been shown to represent the best on treatment predictor of response. In addition to these well known factors, very recently, a single nucleotide polymorphism (SNP) upstream of the gene IL28B on chromosome 19, coding for IFN-lambda 3 has been identified as associated with both spontaneous and treatment induced HCV RNA clearance.
We have developed the molecular technique needed to evaluate this polymorphism in our laboratory. This technical process was a consequence of the genetics expertise of our research Institute. We have also performed a valuable comparison of the different methods to evaluate this polymorphism. Comparison of different technologies allow us to know the rate of variability between the different assays used.
With this methodology we have evaluated "a posteriori" patients previously enrolled in Randomized Controlled Trial. The results of these studies confirmed the association between IL28B CC allele and a favorable outcome of HCV infection in our geographic area (Mangia et al Gastroenterology 2010; Mangia et al Hepatology 2010, AASLD presentation). We are now interested in prospective evaluation of patients referring to our center at the aim of understanding whether there are differences in the rates of IL28B frequencies in patients with different HCV genotypes.
In fact, we hypothesize that the frequency of IL28B might be different according with different HCV genotypes and that this difference may explain the different rates of response to antiviral treatment reported in patients with HCV infection.
Since we lead a collaborative group of hepatologists named AL-LIVER operating in Puglia, Lazio, Basilicata, Sicilia and Campania regions in Italy we would like to extend this evaluation to our collaborative group to explore in a large number of patients whether the prevalence of CC, CT and TT genotypes is inversely associated with HCV G1, 4, 3 and 2.
Read the detailed description
This study is a prevalence study involving naïve patients and without links with treatment. Five hundred patients with HCV infection consecutively observed during 2011 will be requested to sign an informed consent at the aim to be tested for genetics. The study will be evaluated and approved by the Central Ethic Committee. It will have a planned duration of 12 months and will involve 15 centers.
All the HCV infected patients previously untreated can be enrolled once they have signed the Informed consent for genetic testing.
Each patient enrolled at the single center will be evaluated for demographical, virological, biochemical, histological and genetic (IL28B) characteristics. In case of unavailable liver biopsy at least APRI score and Fibroscan evaluation should be used to assess the severity of the underlying liver disease. All the blood specimens will be stored and evaluated by a pre-developed TaqMan allelic discrimination assay (Applied Biosystem) or by direct sequencing for IL28B genetic variation. A serum sample will be also stored to evaluate HCV genotype and HCV RNA levels.
Data will be collected in a database that can be used in the future to select patients needing antiviral treatment.
The association between IL28B variants and the other predictors will be explored by means of descriptive statistical analyses. Number of patients, mean, standard deviation, median will be calculated for continuous variables. Absolute frequencies and per cent will be used to describe frequencies parameters
- Conditions
- Liver Disease
- Being tested
- genotyping and/or sequencing
- Keywords
- Possible association, between severity, IL28B genetic variants, patients, different HCV genotypes
- Medical subject headings
- Liver Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
genotyping and/or sequencingGenetic
genotyping and/or sequencing DNA for IL28
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Sep 2011 (estimated)
- Study startSep 2011
- Primary completionSep 2012
- Study completionSep 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (6)Papers the sponsor has linked to this study.
- Other trials for Liver DiseaseStudies of the same condition, open and under way.
- 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
- Cohort
- Time perspective
- Prospective
- Enrolment
- 500 participants (actual)
Sponsor and investigators
- Lead sponsor
- Casa Sollievo della Sofferenza IRCCS
- Sponsor type
- University, hospital or other
- Collaborators
- INMI L Spallanzani IRCCS Roma, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Azienda Ospedaliera San Camillo Forlanini, Fondazione IRCCS Policlinico San Matteo di Pavia, Azienda ospedaliera Garibaldi Nesinma Catania, Azienda Ospedaliero-Universitaria Careggi, University of Milan, Catholic University, Italy, Ospedale Francesco Ferrari, Ospedale di Canosa di Puglia, Ospedale di Venosa, Clinica Santa Rita Bari, Ospedale SS. Annunziata, Taranto, Ospedali Riuniti di Foggia
- Responsible party
- Principal investigator, Alessandra Mangia, Casa Sollievo della Sofferenza IRCCS
- Investigators
- Alessandra Mangia, MD, Principal investigator, Liver Unit, Casa Sollievo della Sofferenza
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01437969
- Sponsor's protocol ID
- EPAT-IL28B
- Status last verified
- Aug 2023
- First submitted
- 20 Sep 2011
- Last updated
- 30 Aug 2023
- Results posted
- No
Publications
Ge D, Fellay J, Thompson AJ, Simon JS, Shianna KV, Urban TJ, Heinzen EL, Qiu P, Bertelsen AH, Muir AJ, Sulkowski M, McHutchison JG, Goldstein DB. Genetic variation in IL28B predicts hepatitis C treatment-induced viral clearance. Nature. 2009 Sep 17;461(7262):399-401. doi: 10.1038/nature08309. Epub 2009 Aug 16.
PubMed 19684573Suppiah V, Moldovan M, Ahlenstiel G, Berg T, Weltman M, Abate ML, Bassendine M, Spengler U, Dore GJ, Powell E, Riordan S, Sheridan D, Smedile A, Fragomeli V, Muller T, Bahlo M, Stewart GJ, Booth DR, George J. IL28B is associated with response to chronic hepatitis C interferon-alpha and ribavirin therapy. Nat Genet. 2009 Oct;41(10):1100-4. doi: 10.1038/ng.447. Epub 2009 Sep 13.
PubMed 19749758Tanaka Y, Nishida N, Sugiyama M, Kurosaki M, Matsuura K, Sakamoto N, Nakagawa M, Korenaga M, Hino K, Hige S, Ito Y, Mita E, Tanaka E, Mochida S, Murawaki Y, Honda M, Sakai A, Hiasa Y, Nishiguchi S, Koike A, Sakaida I, Imamura M, Ito K, Yano K, Masaki N, Sugauchi F, Izumi N, Tokunaga K, Mizokami M. Genome-wide association of IL28B with response to pegylated interferon-alpha and ribavirin therapy for chronic hepatitis C. Nat Genet. 2009 Oct;41(10):1105-9. doi: 10.1038/ng.449. Epub 2009 Sep 13.
PubMed 19749757Thompson AJ, Muir AJ, Sulkowski MS, Ge D, Fellay J, Shianna KV, Urban T, Afdhal NH, Jacobson IM, Esteban R, Poordad F, Lawitz EJ, McCone J, Shiffman ML, Galler GW, Lee WM, Reindollar R, King JW, Kwo PY, Ghalib RH, Freilich B, Nyberg LM, Zeuzem S, Poynard T, Vock DM, Pieper KS, Patel K, Tillmann HL, Noviello S, Koury K, Pedicone LD, Brass CA, Albrecht JK, Goldstein DB, McHutchison JG. Interleukin-28B polymorphism improves viral kinetics and is the strongest pretreatment predictor of sustained virologic response in genotype 1 hepatitis C virus. Gastroenterology. 2010 Jul;139(1):120-9.e18. doi: 10.1053/j.gastro.2010.04.013. Epub 2010 Apr 24.
PubMed 20399780Mangia A, Thompson AJ, Santoro R, Piazzolla V, Tillmann HL, Patel K, Shianna KV, Mottola L, Petruzzellis D, Bacca D, Carretta V, Minerva N, Goldstein DB, McHutchison JG. An IL28B polymorphism determines treatment response of hepatitis C virus genotype 2 or 3 patients who do not achieve a rapid virologic response. Gastroenterology. 2010 Sep;139(3):821-7, 827.e1. doi: 10.1053/j.gastro.2010.05.079. Epub 2010 Jun 2.
PubMed 20621700Afdhal NH, McHutchison JG, Zeuzem S, Mangia A, Pawlotsky JM, Murray JS, Shianna KV, Tanaka Y, Thomas DL, Booth DR, Goldstein DB; Pharmacogenetics and Hepatitis C Meeting Participants. Hepatitis C pharmacogenetics: state of the art in 2010. Hepatology. 2011 Jan;53(1):336-45. doi: 10.1002/hep.24052.
PubMed 21254181
Study at a glance
From the registry record, last updated by the sponsor on 30 Aug 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pharmacogenomics Study on IL28B Genetic Variants in Italian Patients With HCV Chronic Infection naïve to Antiviral Treatment.
- ClinicalTrials.gov ID
- NCT01437969
- Acronym / sponsor ID
- EPAT-IL28B
- Conditions
- Liver Disease
- Keywords
- Possible association, between severity, IL28B genetic variants, patients, different HCV genotypes
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 500 participants (actual)
- Lead sponsor
- Casa Sollievo della Sofferenza IRCCSUniversity, hospital or other
- Collaborators
- INMI L Spallanzani IRCCS Roma, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Azienda Ospedaliera San Camillo Forlanini, Fondazione IRCCS Policlinico San Matteo di Pavia, Azienda ospedaliera Garibaldi Nesinma Catania, Azienda Ospedaliero-Universitaria Careggi, University of Milan, Catholic University, Italy, Ospedale Francesco Ferrari, Ospedale di Canosa di Puglia, Ospedale di Venosa, Clinica Santa Rita Bari, Ospedale SS. Annunziata, Taranto, Ospedali Riuniti di Foggia
- Study start
- Sep 2011
- Primary completion
- Sep 2012 (actual)
- Study completion
- Sep 2022 (actual)
- First posted
- 21 Sep 2011 (estimated)
- 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.
More than 1.5 millions individuals are infected with HCV in Italy. They are at risk to develop related morbidity and mortality from cirrhosis and hepatocellular carcinoma, unless the evolution of their disease is halted by treatment-induced HCV RNA clearance. Indeed, it is well recognized that a curative antiviral treatment, leading to HCV RNA undetectability 24 weeks after the end of therapy, may prevent the occurrence of complications of HCV chronic liver disease.
Several pre-treatment host and viral factors have been associated with the outcome of pegylated Interferon and Ribavirin treatment. These predictors are relevant as the ability to identify patients with the highest likelihood of achieving HCV RNA clearance may increase the number of patients who agree to be treated and who maintain their adherence to treatment.
Several pre-treatment predictors as HCV genotype, HCV viral load, age, gender, body mass index, stage of fibrosis and race are very well recognized and have been used for many years during the treatment decision-making process. Based on studies of viral kinetics, HCV RNA undetectable at week 4 on treatment has been shown to represent the best on treatment predictor of response. In addition to these well known factors, very recently, a single nucleotide polymorphism (SNP) upstream of the gene IL28B on chromosome 19, coding for IFN-lambda 3 has been identified as associated with both spontaneous and treatment induced HCV RNA clearance.
We have developed the molecular technique needed to evaluate this polymorphism in our laboratory. This technical process was a consequence of the genetics expertise of our research Institute. We have also performed a valuable comparison of the different methods to evaluate this polymorphism. Comparison of different technologies allow us to know the rate of variability between the different assays used.
With this methodology we have evaluated "a posteriori" patients previously enrolled in Randomized Controlled Trial. The results of these studies confirmed the association between IL28B CC allele and a favorable outcome of HCV infection in our geographic area (Mangia et al Gastroenterology 2010; Mangia et al Hepatology 2010, AASLD presentation). We are now interested in prospective evaluation of patients referring to our center at the aim of understanding whether there are differences in the rates of IL28B frequencies in patients with different HCV genotypes.
In fact, we hypothesize that the frequency of IL28B might be different according with different HCV genotypes and that this difference may explain the different rates of response to antiviral treatment reported in patients with HCV infection.
Since we lead a collaborative group of hepatologists named AL-LIVER operating in Puglia, Lazio, Basilicata, Sicilia and Campania regions in Italy we would like to extend this evaluation to our collaborative group to explore in a large number of patients whether the prevalence of CC, CT and TT genotypes is inversely associated with HCV G1, 4, 3 and 2.
Detailed description
This study is a prevalence study involving naïve patients and without links with treatment. Five hundred patients with HCV infection consecutively observed during 2011 will be requested to sign an informed consent at the aim to be tested for genetics. The study will be evaluated and approved by the Central Ethic Committee. It will have a planned duration of 12 months and will involve 15 centers.
All the HCV infected patients previously untreated can be enrolled once they have signed the Informed consent for genetic testing.
Each patient enrolled at the single center will be evaluated for demographical, virological, biochemical, histological and genetic (IL28B) characteristics. In case of unavailable liver biopsy at least APRI score and Fibroscan evaluation should be used to assess the severity of the underlying liver disease. All the blood specimens will be stored and evaluated by a pre-developed TaqMan allelic discrimination assay (Applied Biosystem) or by direct sequencing for IL28B genetic variation. A serum sample will be also stored to evaluate HCV genotype and HCV RNA levels.
Data will be collected in a database that can be used in the future to select patients needing antiviral treatment.
The association between IL28B variants and the other predictors will be explored by means of descriptive statistical analyses. Number of patients, mean, standard deviation, median will be calculated for continuous variables. Absolute frequencies and per cent will be used to describe frequencies parameters
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- HCV infected patients previously untreated
Key inclusion criteria (1 listed)
- Patients with chronic HCV infection irrespective of HCV genotype
Key exclusion criteria (1 listed)
- HCV infected patients previously treated with antiviral drugs; co-infected Patients with HIV or Hepatitis B virus (HBsAg positive)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| genotyping and/or sequencinggenotyping and/or sequencing DNA for IL28 | Genetic | – |
Primary outcome
Not reported in the source record.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Aug 2023.
- Background: PubMed 19684573Ge D, Fellay J, Thompson AJ, Simon JS, Shianna KV, Urban TJ, Heinzen EL, Qiu P, Bertelsen AH, Muir AJ, Sulkowski M, McHutchison JG, Goldstein DB. Genetic variation in IL28B predicts hepatitis C treatment-induced viral clearance. Nature. 2009 Sep 17;461(7262):399-401. doi: 10.1038/nature08309. Epub 2009 Aug 16.
- Background: PubMed 19749758Suppiah V, Moldovan M, Ahlenstiel G, Berg T, Weltman M, Abate ML, Bassendine M, Spengler U, Dore GJ, Powell E, Riordan S, Sheridan D, Smedile A, Fragomeli V, Muller T, Bahlo M, Stewart GJ, Booth DR, George J. IL28B is associated with response to chronic hepatitis C interferon-alpha and ribavirin therapy. Nat Genet. 2009 Oct;41(10):1100-4. doi: 10.1038/ng.447. Epub 2009 Sep 13.
- Background: PubMed 19749757Tanaka Y, Nishida N, Sugiyama M, Kurosaki M, Matsuura K, Sakamoto N, Nakagawa M, Korenaga M, Hino K, Hige S, Ito Y, Mita E, Tanaka E, Mochida S, Murawaki Y, Honda M, Sakai A, Hiasa Y, Nishiguchi S, Koike A, Sakaida I, Imamura M, Ito K, Yano K, Masaki N, Sugauchi F, Izumi N, Tokunaga K, Mizokami M. Genome-wide association of IL28B with response to pegylated interferon-alpha and ribavirin therapy for chronic hepatitis C. Nat Genet. 2009 Oct;41(10):1105-9. doi: 10.1038/ng.449. Epub 2009 Sep 13.
- Background: PubMed 20399780Thompson AJ, Muir AJ, Sulkowski MS, Ge D, Fellay J, Shianna KV, Urban T, Afdhal NH, Jacobson IM, Esteban R, Poordad F, Lawitz EJ, McCone J, Shiffman ML, Galler GW, Lee WM, Reindollar R, King JW, Kwo PY, Ghalib RH, Freilich B, Nyberg LM, Zeuzem S, Poynard T, Vock DM, Pieper KS, Patel K, Tillmann HL, Noviello S, Koury K, Pedicone LD, Brass CA, Albrecht JK, Goldstein DB, McHutchison JG. Interleukin-28B polymorphism improves viral kinetics and is the strongest pretreatment predictor of sustained virologic response in genotype 1 hepatitis C virus. Gastroenterology. 2010 Jul;139(1):120-9.e18. doi: 10.1053/j.gastro.2010.04.013. Epub 2010 Apr 24.
- Background: PubMed 20621700Mangia A, Thompson AJ, Santoro R, Piazzolla V, Tillmann HL, Patel K, Shianna KV, Mottola L, Petruzzellis D, Bacca D, Carretta V, Minerva N, Goldstein DB, McHutchison JG. An IL28B polymorphism determines treatment response of hepatitis C virus genotype 2 or 3 patients who do not achieve a rapid virologic response. Gastroenterology. 2010 Sep;139(3):821-7, 827.e1. doi: 10.1053/j.gastro.2010.05.079. Epub 2010 Jun 2.
- Background: PubMed 21254181Afdhal NH, McHutchison JG, Zeuzem S, Mangia A, Pawlotsky JM, Murray JS, Shianna KV, Tanaka Y, Thomas DL, Booth DR, Goldstein DB; Pharmacogenetics and Hepatitis C Meeting Participants. Hepatitis C pharmacogenetics: state of the art in 2010. Hepatology. 2011 Jan;53(1):336-45. doi: 10.1002/hep.24052.
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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.
Alessandra Mangia, MD principal investigator
Liver Unit, Casa Sollievo della Sofferenza
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Liver Disease, run by Casa Sollievo della Sofferenza IRCCS at 1 site in Italy.
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 1 inclusion and 1 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: finished, as of the sponsor's last update on 30 Aug 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01437969, which also lists 6 linked publications.
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 30 Aug 2023; AzTrials last refreshed its copy on 7 Nov 2026.