Chronic Hepatitis CBoce-ParNCT01403181
Effect of Boceprevir on HCV-specific T Cell Responses
An observational study of Chronic Hepatitis C, run by Azienda Ospedaliero-Universitaria di Parma at 1 site in Italy.
Trial summary
Analysis of HCV-specific T cell responses in patients treated with boceprevir to assess whether therapy can induce restoration of the T cell function and to what extent this recovery can be achieved Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Chronic Hepatitis C
- What is being tested?
- Boceprevir
- Type of treatment
- Pill or oral medicine
- How many people
- 30 participants
- Where
- 1 siteItaly
- Study dates
- Apr 2012to Oct 2013
- 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: Naïve genotype 1 chronic hepatitis C patients
Who may be able to join
- Subjects must meet all of the following inclusion criteria to be eligible for participation in this study.
- Male or female, aged from 18 to 70 years old, inclusive.
- Willing and able to provide written informed consent
- Chronic HCV infection for at least 6 month prior to baseline (Day 1) in subjects currently positive for HCV-RNA and anti-HCV antibody documented by:
- A positive anti-HCV antibody test, positive HCV-RNA assay, or HCV genotype test at least 6 month prior to baseline (Day 1) or
- A liver biopsy performed prior to baseline (Day 1) with evidence of chronic HCV infection
Show all 13Show fewer
- Subjects must have liver biopsy results (performed no more than two years prior the screening) indicating the absence of cirrhosis
- HCV infection limited to genotype 1
- Detectable plasma HCV-RNA at screening
- BMI between 18 and 36 Kg/m2
- Eligible subjects must also be HCV treatment-naïve, defined as no prior exposure to PEG-INF and ribavirin, and must be eligible to standard of care therapy with PEG/RBV
- Subjects must have the following laboratory parameters at screening:
- ALT and AST ≤ 5 x upper limit of normal range (ULN) Hemoglobin (Hb) ≥ 12 g/dl WBC ≥ 2.500 cells/μL with absolute neutrophil count ≥ 1500 cells/μL If a woman of childbearing potential, must have negative serum β-human chorionic gonadotropin (β-HCG) pregnancy test documented at the screening visit and a negative serum or urine pregnancy test before the first dose of study drug to ensure that they are not pregnant at the time of starting treatment A female subjects of childbearing potential and nonvasectomized male subjects with a female partners of childbearing potential must agree that they and their partner will use effective contraception (two separate forms of contraception simultaneously, one of which must be a male condom with spermicide) from screening throughout the duration of study treatment and for at least 7 months
Who cannot join
- Pregnant women or women who may wish to become pregnant during the course of the study
- Male with a female who is pregnant or is planning to become pregnant within seven month the study of anticipated last dose of ribavirin
- Evidence of infection or co-infection with a no-genotype 1 HCV-strain
- History of hemoglobinopathy
- History of sarcoidosis
- History of invasive malignancy diagnosed or treated within 5 years.
Show all 19Show fewer
- Untreated or significant psychiatric illnesses including severe depression, schizophrenia, psychosis, history of a suicide attempt
- Co-infection with HBV or HIV
- Chronic use of systemic immunosuppressive agents
- Presence of autoimmune disorders; subjects with treated hypothyroidism with normal TSH may be enrolled
- History of significant cardiac disease
- Clinical evidence of chronic pulmonary disease
- Known cirrhosis
- History of solid organ transplantation
- Suspicion of hepatocellular carcinoma
- Chronic liver disease of a non-HCV etiology
- Ongoing alcohol abuse
- History of clinical relevant drug abuse
- Positive urine screen for cocaine, opiate etc, or methadone use
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Effect of Boceprevir Therapy on HCV-specific T Cell Responses: Perspectives of Immune Monitoring and Immune Therapy
Analysis of HCV-specific T cell responses in patients treated with boceprevir to assess whether therapy can induce restoration of the T cell function and to what extent this recovery can be achieved
Read the detailed description
Reconstitution of the antiviral T cell function may represent a component of the anti-viral effect of protease inhibitors. If T cell responsiveness is restored under therapy, potentiation of anti-viral T cell functions by exogenous T cell stimulation might be exploited to complement and to further improve response to available therapies. Monitoring the T cell function might also be useful to predict more accurately response to therapy.
To address these issues, phenotype and function of HCV-specific T cells will be analyzed longitudinally before, during and after therapy in naïve genotype 1 chronic hepatitis C patients treated with peginterferon plus ribavirin or with peginterferon and ribavirin plus boceprevir. To analyze the global CD4 and CD8 reactivity against all structural and non-structural HCV proteins a wide panel of peptides corresponding to the whole HCV genome of genotype 1 will be employed. To further analyze CD8 reactivity, HLA-A2/peptide tetramers will be used in HLA-A2 positive patients to directly quantify ex vivo HCV-specific CD8 cells circulating in the peripheral blood.The T cell function will be analyzed as capacity of expansion in vitro, cytokine production and cytotoxicity.
- Conditions
- Chronic Hepatitis C
- Being tested
- Boceprevir
- Keywords
- HCV, T cells, cytokines, cytotoxicity, proliferation
- Medical subject headings
- Hepatitis C, Chronic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BoceprevirDrug
Also called Peginterferon alfa-2b and ribavirin
In the experimental arm boceprevir (800 mg orally three times daily), PEG-IFN and ribavirin will be given for 24 weeks after the lead-in; the patients who will have undetectable HCV-RNA at week 8 will stop treatment at week 28; those who will be HCV-RNA positive at any visit between week 8 and 24 will receive an additional 20 weeks of PEG + RBV. Treatment will be discontinued if HCV-RNA is positive at week 24.
Immunological analysis will be performed longitudinally at the following time points: week -4, 0, 4 (end of lead-in), 8, 12, 24, 48, week 24 of follow-up. HCV-RNA will be quantified at the same time points and viremia will be correlated with immunological data.
| Study group | Role | What they receive |
|---|---|---|
| Chronic hepatitis C | * 10 naïve genotype 1 chronic hepatitis C patients treated with PEG plus RBV (control arm)
* 20 naïve genotype 1 chronic hepatitis C patients treated with a response guided therapy consisting of Boceprevir in combination with PEG plus RBV (experimental arm) Receives: Drug: Boceprevir |
What is being measured
The primary outcome is the main question the study is designed to answer.
Levels of HCV-specific T cell functions before, during and after therapy to measure functional restoration induced by therapy
Capacity of expansion, cytokine production (IFN-γ, IL-2 and TNF-α) and cytotoxicity expressed by HCV-specific T cells will be analyzed longitudinally at different time points before, during and after therapy
Measured: 2 years
Secondary outcomes (1)
Correlation of quality and intensity of pre-treatment HCV-specific T cell responses with outcome of therapy
To assess whether different levels of efficiency of pre-treatment antiviral T cell responses can predict response to treatment.
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Jul 2011 (estimated)
- Study startApr 2012
- Primary completionOct 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Chronic Hepatitis CStudies 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
- Time perspective
- Prospective
- Enrolment
- 30 participants (actual)
Sponsor and investigators
- Lead sponsor
- Azienda Ospedaliero-Universitaria di Parma
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Carlo Ferrari, Azienda Ospedaliero-Universitaria di Parma
- Investigators
- Carlo Ferrari, MD, Principal investigator, Azienda Ospedaliero-Universitaria di Parma
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01403181
- Sponsor's protocol ID
- AZOSPA
- Acronym
- Boce-Par
- Status last verified
- Nov 2013
- First submitted
- 26 Jul 2011
- Last updated
- 6 Nov 2013
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 6 Nov 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of Boceprevir Therapy on HCV-specific T Cell Responses: Perspectives of Immune Monitoring and Immune Therapy
- ClinicalTrials.gov ID
- NCT01403181
- Acronym / sponsor ID
- Boce-Par / AZOSPA
- Conditions
- Chronic Hepatitis C
- Keywords
- HCV, T cells, cytokines, cytotoxicity, proliferation
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 30 participants (actual)
- Lead sponsor
- Azienda Ospedaliero-Universitaria di ParmaUniversity, hospital or other
- Study start
- Apr 2012
- Primary completion
- Oct 2013 (actual)
- First posted
- 27 Jul 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.
Analysis of HCV-specific T cell responses in patients treated with boceprevir to assess whether therapy can induce restoration of the T cell function and to what extent this recovery can be achieved
Detailed description
Reconstitution of the antiviral T cell function may represent a component of the anti-viral effect of protease inhibitors. If T cell responsiveness is restored under therapy, potentiation of anti-viral T cell functions by exogenous T cell stimulation might be exploited to complement and to further improve response to available therapies. Monitoring the T cell function might also be useful to predict more accurately response to therapy.
To address these issues, phenotype and function of HCV-specific T cells will be analyzed longitudinally before, during and after therapy in naïve genotype 1 chronic hepatitis C patients treated with peginterferon plus ribavirin or with peginterferon and ribavirin plus boceprevir. To analyze the global CD4 and CD8 reactivity against all structural and non-structural HCV proteins a wide panel of peptides corresponding to the whole HCV genome of genotype 1 will be employed. To further analyze CD8 reactivity, HLA-A2/peptide tetramers will be used in HLA-A2 positive patients to directly quantify ex vivo HCV-specific CD8 cells circulating in the peripheral blood.The T cell function will be analyzed as capacity of expansion in vitro, cytokine production and cytotoxicity.
Study design
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Chronic hepatitis C | – | Drug: Boceprevir* 10 naïve genotype 1 chronic hepatitis C patients treated with PEG plus RBV (control arm) * 20 naïve genotype 1 chronic hepatitis C patients treated with a response guided therapy consisting of Boceprevir in combination with PEG plus RBV (experimental arm) |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Naïve genotype 1 chronic hepatitis C patients
Key inclusion criteria (13 listed)
- Subjects must meet all of the following inclusion criteria to be eligible for participation in this study.
- Male or female, aged from 18 to 70 years old, inclusive.
- Willing and able to provide written informed consent
- Chronic HCV infection for at least 6 month prior to baseline (Day 1) in subjects currently positive for HCV-RNA and anti-HCV antibody documented by:
- A positive anti-HCV antibody test, positive HCV-RNA assay, or HCV genotype test at least 6 month prior to baseline (Day 1) or
Key exclusion criteria (19 listed)
- Pregnant women or women who may wish to become pregnant during the course of the study
- Male with a female who is pregnant or is planning to become pregnant within seven month the study of anticipated last dose of ribavirin
- Evidence of infection or co-infection with a no-genotype 1 HCV-strain
- History of hemoglobinopathy
- History of sarcoidosis
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 |
|---|---|---|
| BoceprevirAlso: Peginterferon alfa-2b and ribavirinIn the experimental arm boceprevir (800 mg orally three times daily), PEG-IFN and ribavirin will be given for 24 weeks after the lead-in; the patients who will have undetectable HCV-RNA at week 8 will stop treatment at week 28; those who will be HCV-RNA positive at any visit between week 8 and 24 will receive an additional 20 weeks of PEG + RBV. Treatment will be discontinued if HCV-RNA is positive at week 24. Immunological analysis will be performed longitudinally at the following time points: week -4, 0, 4 (end of lead-in), 8, 12, 24, 48, week 24 of follow-up. HCV-RNA will be quantified at the same time points and viremia will be correlated with immunological data. | Drug | Chronic hepatitis C |
Primary outcome
Levels of HCV-specific T cell functions before, during and after therapy to measure functional restoration induced by therapy
Time frame: 2 years
Capacity of expansion, cytokine production (IFN-γ, IL-2 and TNF-α) and cytotoxicity expressed by HCV-specific T cells will be analyzed longitudinally at different time points before, during and after therapy
1 secondary outcome
Correlation of quality and intensity of pre-treatment HCV-specific T cell responses with outcome of therapy
Time frame: 2 years
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 6 Nov 2013.
Related trials for Chronic Hepatitis C
RecruitingObservational study
Evaluation of Patients With Liver Disease
Hepatitis D, Hepatitis C
Active, not recruitingPhase 4
People With CHC Who Achieved a Sustained Virological Response Following Therapy With Direct Acting Antiviral Agents
Diabetes Mellitus, Hepatitis C, Chronic
RecruitingObservational study
"Constitution of a Biological Collection to Establish Preclinical Translational Models for the Study of Tumors and Chronic Liver Diseases".
Chronic Liver Disease and Cirrhosis, Liver Cancer
Active, not recruitingPhase 4
Sofosbuvir/Velpatasvir Treatment of Chronic Hepatitis C During Pregnancy
Hepatitis C, Chronic, Pregnancy; Infection
Enrolling by invitationObservational study
Comparative Autoantibody and Immunologic Cell Marker Study
Autoimmune Diseases, Lupus Erythematosus, Systemic
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.
Carlo Ferrari, MD principal investigator
Azienda Ospedaliero-Universitaria di Parma
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 Chronic Hepatitis C, run by Azienda Ospedaliero-Universitaria di Parma 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 13 inclusion and 19 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 6 Nov 2013. 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.
What does the primary outcome measure?
Levels of HCV-specific T cell functions before, during and after therapy to measure functional restoration induced by therapy (time frame: 2 years). 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 6 Nov 2013.