Chronic Hepatitis CPhase 3ImmunoDualNCT02282709
Effect of ASV and DCV Therapy on the Quality of Immune Status in Chronic HCV Patients
A Phase 3 study testing Daclatasvir and asunaprevir in people with Chronic Hepatitis C, run by Foundation for Liver Research at 1 site in Netherlands.
Trial summary
Rationale: Chronic HCV infection is characterised by a weak HCV specific CD8+ T cell response, due to continuous pressure of high viral load. Treatment of chronic HCV patients with ASV and DCV will result in a significant drop in HCV viral load. 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?
- Daclatasvir and asunaprevir
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 12 participants
- Where
- 1 siteNetherlands
- Study dates
- Feb 2014to Jul 2015
- Phase
- Phase 3
- 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
Who may be able to join
- Patients between 18 and 70 years of age, with a chronic hepatitis C - genotype 1b infection
- Patients are non-responders to previous treatment with peginterferon or conventional interferon plus ribavirin combination therapy
- High viral load (>400,000 IU/ml)
- Indication for antiviral therapy of hepatitis C according to current clinical guidelines
- Written informed consent
Who cannot join
- Decompensated cirrhosis (Child-Pugh Grade B or C)
- Hepatic imaging (ultrasound, CT or MRI) with the evidence of hepatocellular carcinoma within the last 3 months.
- Females who are pregnant or breast-feeding
- History or other evidence of severe illness, malignancy or any other condition which would make the patient, in the opinion of the investigators, unsuitable for the study
- Co-infections with human immunodeficiency virus (HIV) or Hepatitis B virus (HBV)
- Presence of contra-indications for antiviral therapy with ASV and DCV:
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- Interfering substance abuse, such as high alcohol intake (indicator: 28 drinks/ week)
- Any exposure to NS3 protease inhibitors or NS5A polymerase inhibitors
- Treatment with peginterferon/ ribavirin within 6 months before start of therapy
- Any other condition which in the opinion of the investigator would make the patient unsuitable for enrollment, or could interfere with the patient participating and completing in the study
Trial locations and contacts
1 site in 1 country.
About this study
Rationale: Chronic HCV infection is characterised by a weak HCV specific CD8+ T cell response, due to continuous pressure of high viral load. Treatment of chronic HCV patients with ASV and DCV will result in a significant drop in HCV viral load. At present, no information is available on the immunological effects of treatment with ASV and DCV, nor on the early effects of viral load reduction caused by a compound that is thought not to possess direct immunomodulatory effects. This information will be crucial for a better understanding of the mechanisms that may limit the effectiveness of treatment, occurrence of viral rebound or relapses during, at the end of treatment or during the follow up period.
Objective: To evaluate in detail the functionality of immune cells in blood in chronic HCV patients before, during and after treatment with ASV and DCV, in an IFN-free regimen.
Read more
Study design: This is an investigator-initiated single center open label study with one arm of 12 patients.
Study population: Adult chronic HCV patients with genotype 1b, who are previous non-responders to the treatment.
Intervention (if applicable): All patients will be treated with twice daily a 200 mg oASV and once daily a 60 mg DCV for 24 weeks.
Main study parameters/endpoints:
- Phenotype and function of blood leukocytes during treatment; frequency of HCV-specific T cells, NK cells and monocytes
- Gene expression levels of leukocyte populations before, during and after treatment
- Gene expression levels of the type I IFN signaling pathway on whole blood samples
- Serum cytokines levels using multiplex platforms
- Conditions
- Chronic Hepatitis C
- Being tested
- Daclatasvir, asunaprevir
- Keywords
- Immunity
- 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.
DaclatasvirDrug
60 mg once daily
asunaprevirDrug
100 mg BID
| Study group | Role | What they receive |
|---|---|---|
| Daclatasvir and asunaprevir | Experimental | daclatasvir 60 mg once daily asunaprevir 100 mg BID Receives: Drug: Daclatasvir; Drug: asunaprevir |
What is being measured
The primary outcome is the main question the study is designed to answer.
HCV-specific T cell phenotype and function (a composite measure of (I) HCV-specific T-cell frequency and (II) phenotypic expression of memory markers and (III) inhibitory receptor markers
Measured: 1 year
NK cell phenotype and function (a composite measure of (I) NK cell frequency and (II) expression of activation and inhibitory markers (III) IFN-y production upon IL-12/IL-18 stimulation and (IV) Perforin granzyme production
Measured: 1 year
Secondary outcomes (3)
Gene expression levels of the type I IFN signaling pathway on whole blood samples measured by multiplex
Measured: 1 year
Gene expression levels of leukocyte populations before, during and after treatment measured by microarray
Measured: 2 years
Serum cytokines levels using multiplex platforms LUMINEX -100
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Nov 2014 (estimated)
- Study startFeb 2014
- Primary completionJul 2015
- Study completionJul 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- 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
- Interventional
- Phase
- Phase 3
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 12 participants (actual)
Sponsor and investigators
- Lead sponsor
- Foundation for Liver Research
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Rob de Knegt, M.D., Principal investigator, Erasmus Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02282709
- Sponsor's protocol ID
- Foundation_LiverR
- Acronym
- ImmunoDual
- Status last verified
- Oct 2015
- First submitted
- 23 Oct 2014
- Last updated
- 19 Oct 2015
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Spaan M, van Oord G, Kreefft K, Hou J, Hansen BE, Janssen HL, de Knegt RJ, Boonstra A. Immunological Analysis During Interferon-Free Therapy for Chronic Hepatitis C Virus Infection Reveals Modulation of the Natural Killer Cell Compartment. J Infect Dis. 2016 Jan 15;213(2):216-23. doi: 10.1093/infdis/jiv391. Epub 2015 Jul 28.
PubMed 26223768
Study at a glance
From the registry record, last updated by the sponsor on 19 Oct 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of ASV and DCV Therapy on the Quality of Immune Status in Chronic HCV Patients
- ClinicalTrials.gov ID
- NCT02282709
- Acronym / sponsor ID
- ImmunoDual / Foundation_LiverR
- Conditions
- Chronic Hepatitis C
- Keywords
- Immunity
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 12 participants (actual)
- Lead sponsor
- Foundation for Liver ResearchUniversity, hospital or other
- Study start
- Feb 2014
- Primary completion
- Jul 2015 (actual)
- Study completion
- Jul 2015 (actual)
- First posted
- 4 Nov 2014 (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.
Rationale: Chronic HCV infection is characterised by a weak HCV specific CD8+ T cell response, due to continuous pressure of high viral load. Treatment of chronic HCV patients with ASV and DCV will result in a significant drop in HCV viral load. At present, no information is available on the immunological effects of treatment with ASV and DCV, nor on the early effects of viral load reduction caused by a compound that is thought not to possess direct immunomodulatory effects. This information will be crucial for a better understanding of the mechanisms that may limit the effectiveness of treatment, occurrence of viral rebound or relapses during, at the end of treatment or during the follow up period.
Objective: To evaluate in detail the functionality of immune cells in blood in chronic HCV patients before, during and after treatment with ASV and DCV, in an IFN-free regimen.
Study design: This is an investigator-initiated single center open label study with one arm of 12 patients.
Study population: Adult chronic HCV patients with genotype 1b, who are previous non-responders to the treatment.
Intervention (if applicable): All patients will be treated with twice daily a 200 mg oASV and once daily a 60 mg DCV for 24 weeks.
Main study parameters/endpoints:
- Phenotype and function of blood leukocytes during treatment; frequency of HCV-specific T cells, NK cells and monocytes
- Gene expression levels of leukocyte populations before, during and after treatment
- Gene expression levels of the type I IFN signaling pathway on whole blood samples
- Serum cytokines levels using multiplex platforms
Study design
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Daclatasvir and asunaprevir | Experimental | Drug: Daclatasvir, Drug: asunaprevirdaclatasvir 60 mg once daily asunaprevir 100 mg BID |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Patients between 18 and 70 years of age, with a chronic hepatitis C - genotype 1b infection
- Patients are non-responders to previous treatment with peginterferon or conventional interferon plus ribavirin combination therapy
- High viral load (>400,000 IU/ml)
- Indication for antiviral therapy of hepatitis C according to current clinical guidelines
- Written informed consent
Key exclusion criteria (10 listed)
- Decompensated cirrhosis (Child-Pugh Grade B or C)
- Hepatic imaging (ultrasound, CT or MRI) with the evidence of hepatocellular carcinoma within the last 3 months.
- Females who are pregnant or breast-feeding
- History or other evidence of severe illness, malignancy or any other condition which would make the patient, in the opinion of the investigators, unsuitable for the study
- Co-infections with human immunodeficiency virus (HIV) or Hepatitis B virus (HBV)
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 |
|---|---|---|
| Daclatasvir60 mg once daily | Drug | Daclatasvir and asunaprevir |
| asunaprevir100 mg BID | Drug | Daclatasvir and asunaprevir |
Primary outcome
HCV-specific T cell phenotype and function (a composite measure of (I) HCV-specific T-cell frequency and (II) phenotypic expression of memory markers and (III) inhibitory receptor markers
Time frame: 1 year
NK cell phenotype and function (a composite measure of (I) NK cell frequency and (II) expression of activation and inhibitory markers (III) IFN-y production upon IL-12/IL-18 stimulation and (IV) Perforin granzyme production
Time frame: 1 year
3 secondary outcomes
Gene expression levels of the type I IFN signaling pathway on whole blood samples measured by multiplex
Time frame: 1 year
Gene expression levels of leukocyte populations before, during and after treatment measured by microarray
Time frame: 2 years
Serum cytokines levels using multiplex platforms LUMINEX -100
Time frame: 1 year
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 19 Oct 2015.
- Derived from this study: PubMed 26223768Spaan M, van Oord G, Kreefft K, Hou J, Hansen BE, Janssen HL, de Knegt RJ, Boonstra A. Immunological Analysis During Interferon-Free Therapy for Chronic Hepatitis C Virus Infection Reveals Modulation of the Natural Killer Cell Compartment. J Infect Dis. 2016 Jan 15;213(2):216-23. doi: 10.1093/infdis/jiv391. Epub 2015 Jul 28.
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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.
Rob de Knegt, M.D. principal investigator
Erasmus Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Daclatasvir and asunaprevir in people with Chronic Hepatitis C, run by Foundation for Liver Research at 1 site in Netherlands.
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 5 inclusion and 10 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 19 Oct 2015. 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 Netherlands. 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.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
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?
HCV-specific T cell phenotype and function (a composite measure of (I) HCV-specific T-cell frequency and (II) phenotypic expression of memory markers and (III) inhibitory receptor markers (time frame: 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?
On the ClinicalTrials.gov record for NCT02282709, which also lists 1 linked publication.
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 19 Oct 2015.