Hepatitis C, ChronicPhase 4HEPCOG-IINCT02292966
Impact of HCV Treatment on Neurocognitive Functions and Brain Metabolism
A Phase 4 study testing DCV/ASV/BCV in people with Hepatitis C, Chronic, run by Kirby Institute at 2 sites in Australia.
Trial summary
The purpose of this study is to examine whether neurocognitive impairments experienced by patients with chronic hepatitis C virus (HCV) infection can be reversed by treating HCV, with a new combination of direct acting antiviral drugs (daclatasvir (DCV), asunaprevir (ASV) and beclabuvir (BCV)). Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Hepatitis C, Chronic
- What is being tested?
- DCV/ASV/BCV
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 2 sitesAustralia
- Study dates
- Jul 2015to Jun 2016
- Phase
- Phase 4
- 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 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Aged 18 to 65 years
- Chronic HCV infection as documented by positive HCV RNA at screening and positive HCV RNA or anti-HCV antibody at least 6 months prior to screening
- HCV genotype 1 - mixed subtype, indeterminate subtype or other variants of genotype 1 are permissible
- Non-advanced cirrhotic defined as FibroScan ≤9.6 kPA at screening
- HCV treatment naïve
- Seronegative for HIV and HBsAg
Show all 12Show fewer
- HCV RNA level of ≥104 IU/mL (10,000 IU/mL)
- Body Mass Index (BMI) between 18 and 35 kg/m2
- Women of childbearing potential (WOCBP) must:
- Have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/mL or equivalent units of HCG) within 24 hours prior to the start of study drug ii. Not be breastfeeding iii. Agree to follow instructions for methods of contraception for the duration of the treatment and for five weeks post-treatment completion
- Men who are sexually active with WOCBP must agree to follow instructions for methods of contraception for the duration of the treatment and for 14 weeks post-treatment completion
- Sufficient proficiency in English to complete the neurocognitive assessment, as judged by the investigator
Who cannot join
- Target disease
- Infected with HCV other than genotype 1
- Medical history and concurrent diseases
- Current hazardous consumption of alcohol, defined by an AUDIT-C score ≥4 for men and ≥3 for women
- Illicit substance use, identified by urinary drug test at screening
- Past history of non HCV-related CNS disorder, including seizures and traumatic brain injury
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- Currently on an SSRI or other neuropsychiatric therapy
- Liver or any other organ transplant other than cornea and hair
- Current or known history of cancer (except in situ carcinoma of the cervix or adequately treated basal or squamous cell carcinoma of the skin) within 5 years prior to enrolment
- Evidence of a medical condition contributing to chronic liver disease other than HCV (such, but not limited to: hemochromatosis, autoimmune hepatitis, metabolic liver disease, alcohol liver disease)
- Any gastrointestinal disease or surgical procedure that may impact the absorption of study drug (subjects who have cholecystectomy are permitted to enter the study)
- Known history of coagulopathy including, but not limited to, hemophilia
- Uncontrolled diabetes defined as HbA1c >7% at screening
- Confirmed, uncontrolled hypertension (any screening systolic blood pressure ≥160 mmHg or diastolic blood pressure ≥100 mmHg should be excluded unless discussed with the study medical monitor)
- Inability to tolerate oral medication
- Poor venous access
- Any other medical, psychiatric and/or social reason which, in the opinion of the investigator would make the subject inappropriate for the study
- Physical and Laboratory Test Findings
- ALT ≥ 5 x ULN
- Total Bilirubin ≥ 34 µmol/L (≥ 2 mg/dl), unless subject has documented history of Gilbert's disease
- INR ≥ 1.3
- Albumin < 3.5 g/dL (35g/L)
- Platelets < 100 x 109 cells/L
- ANC < 0.75 x 109 cells/L
- Hemoglobin < 10 g/dL (100g/L)
- Creatinine clearance (CrCL) ≤ 50 mL/min
- Alpha fetoprotein (AFP) > 50ng/mL
- QTcF or QTcB > 580mSec
- Positive HBsAg, HIV-1 or HIV-2 Ab
- Allergies and Adverse Drug Reaction
- History of hypersensitivity to drugs with a similar biochemical structure to DCV, ASV or BCV
- Any other criteria or know contraindication that would exclude the subject from receiving DCV, ASV or BCV Prohibited treatments and/or Therapies
- Exposure to any investigational drug or placebo within 4 weeks of study drug administration
- Refer to 5.5 for prohibited and/or restricted treatments during and post-treatment Sex and reproductive status
- Males and females who do not or are unable to meet the requirements outlined in Inclusion Criterias 9 and 10
- Other Exclusion Criteria
- Prisoners or subjects who are involuntarily incarcerated
- Subjects who are compulsorily detained for treatment of either a psychiatric or physical (e.g. infection disease) illness
Trial locations and contacts
2 sites in 1 country.
Australia2 sites
St Vincent's Hospital
Sydney, New South Wales, 2010
Westmead Hospital
Westmead, New South Wales, 2145
About this study
Official title: Impact of HCV Eradication on Neurocognitive Functions and CNS Metabolism: a Trial of Daclatasvir, Asunaprevir and Beclabuvir for Patients With HCV Genotype 1 Infection
The purpose of this study is to examine whether neurocognitive impairments experienced by patients with chronic hepatitis C virus (HCV) infection can be reversed by treating HCV, with a new combination of direct acting antiviral drugs (daclatasvir (DCV), asunaprevir (ASV) and beclabuvir (BCV)). The study will assess the effect of HCV on the central nervous system (CNS) by assessing neurocognitive function and brain injury prior to treatment, and comparing it to the end of treatment, and 4, 12 and 24 weeks after treatment.
Read the detailed description
This study will evaluate the effect of DCV/ASV/BCV on neurocognitive functioning and brain metabolite concentrations in the frontal white matter and the basal ganglia in people with chronic HCV genotype 1 infection, through a comparison of baseline and post-treatment parameters.
This is an open label single arm multi-centre study. All participants will each receive daclatasvir (30mg), asunaprevir (200mg) and beclabuvir (75mg) in a fixed-dose combination oral tablet for twice daily administration with food.
Duration of treatment will be 12 weeks for all subjects followed by 24 weeks of observational follow-up.
- Conditions
- Hepatitis C, Chronic
- Being tested
- DCV/ASV/BCV
- Keywords
- Hepatitis C, Hepatitis, Asunaprevir, Daclatasvir, Beclabuvir, Neurocognitive function, Brain metabolites, Direct acting antiviral therapy
- Medical subject headings
- Hepatitis C, Chronic, Hepatitis C, Hepatitis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DCV/ASV/BCVDrug
Also called Daclatasvir, Asunaprevir, Beclabuvir
Each participant will each receive daclatasvir (30mg), asunaprevir (200mg) and beclabuvir (75mg) in a fixed-dose combination oral tablet for twice daily administration with food.
| Study group | Role | What they receive |
|---|---|---|
| Hepatitis C treatment | Experimental | 12 weeks of DCV/ASV/BCV therapy. Receives: Drug: DCV/ASV/BCV |
What is being measured
The primary outcome is the main question the study is designed to answer.
Neurocognitive functioning
Mean change in neurocognitive functioning (global z-score representing overall neurocognitive performance across CogState, pegboard and colours trails)
Measured: 36 weeks
Brain metabolite concentrations
Mean change in five absolute metabolite concentrations (NAA,Cho, Cr, mlo, glx)
Measured: 36 weeks
Secondary outcomes (8)
Neurocognitive functioning
Mean change in neurocognitive functioning (global z-score representing overall neurocognitive performance across CogState, pegboard and colours trails)
Measured: 12 and 24 weeks
NAA metabolite concentration in the brain
Measured: 12 and 24 weeks
Cho metabolite concentration in the brain
Measured: 12 and 24 weeks
Cr metabolite concentration in the brain
Measured: 12 and 24 weeks
MLO metabolite concentration in the brain
Measured: 12 and 24 weeks
Glx metabolite concentration in the brain
Measured: 12 and 24 weeks
Change in neurocognitive functioning compared between subjects with and without sustained virological response (SVR)
Mean change in neurocognitive functioning (global z-score representing overall neurocognitive performance across CogState, pegboard and colours trails)
Measured: 24 weeks
Change in brain metabolite concentrations compared between subjects with and without sustained virological response (SVR)
Mean change in absolute metabolite concentrations (NAA,Cho, Cr, mlo, glx)
Measured: 24 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Nov 2014 (estimated)
- Study startJul 2015
- Primary completionJun 2016 (estimated)
- Study completionJun 2016 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Hepatitis C, ChronicStudies 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 4
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Kirby Institute
- Sponsor type
- Other government
- Collaborators
- Bristol-Myers Squibb
- Responsible party
- Sponsor
- Investigators
- Gregory Dore, BSc, MBBS, FRACP, MPH, PhD, Principal investigator, Kirby Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02292966
- Sponsor's protocol ID
- VHCRP1304
- Acronym
- HEPCOG-II
- Status last verified
- Jun 2016
- First submitted
- 25 Sep 2014
- Last updated
- 3 Jun 2016
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 3 Jun 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Impact of HCV Eradication on Neurocognitive Functions and CNS Metabolism: a Trial of Daclatasvir, Asunaprevir and Beclabuvir for Patients With HCV Genotype 1 Infection
- ClinicalTrials.gov ID
- NCT02292966
- Acronym / sponsor ID
- HEPCOG-II / VHCRP1304
- Conditions
- Hepatitis C, Chronic
- Keywords
- Hepatitis C, Hepatitis, Asunaprevir, Daclatasvir, Beclabuvir, Neurocognitive function, Brain metabolites, Direct acting antiviral therapy
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Withdrawn
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Kirby InstituteOther government
- Collaborators
- Bristol-Myers Squibb
- Study start
- Jul 2015
- Primary completion
- Jun 2016 (estimated)
- Study completion
- Jun 2016 (estimated)
- First posted
- 18 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.
The purpose of this study is to examine whether neurocognitive impairments experienced by patients with chronic hepatitis C virus (HCV) infection can be reversed by treating HCV, with a new combination of direct acting antiviral drugs (daclatasvir (DCV), asunaprevir (ASV) and beclabuvir (BCV)). The study will assess the effect of HCV on the central nervous system (CNS) by assessing neurocognitive function and brain injury prior to treatment, and comparing it to the end of treatment, and 4, 12 and 24 weeks after treatment.
Detailed description
This study will evaluate the effect of DCV/ASV/BCV on neurocognitive functioning and brain metabolite concentrations in the frontal white matter and the basal ganglia in people with chronic HCV genotype 1 infection, through a comparison of baseline and post-treatment parameters.
This is an open label single arm multi-centre study. All participants will each receive daclatasvir (30mg), asunaprevir (200mg) and beclabuvir (75mg) in a fixed-dose combination oral tablet for twice daily administration with food.
Duration of treatment will be 12 weeks for all subjects followed by 24 weeks of observational follow-up.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Hepatitis C treatment | Experimental | Drug: DCV/ASV/BCV12 weeks of DCV/ASV/BCV therapy. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- Aged 18 to 65 years
- Chronic HCV infection as documented by positive HCV RNA at screening and positive HCV RNA or anti-HCV antibody at least 6 months prior to screening
- HCV genotype 1 - mixed subtype, indeterminate subtype or other variants of genotype 1 are permissible
- Non-advanced cirrhotic defined as FibroScan ≤9.6 kPA at screening
- HCV treatment naïve
Key exclusion criteria (38 listed)
- Target disease
- Infected with HCV other than genotype 1
- Medical history and concurrent diseases
- Current hazardous consumption of alcohol, defined by an AUDIT-C score ≥4 for men and ≥3 for women
- Illicit substance use, identified by urinary drug test at screening
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 |
|---|---|---|
| DCV/ASV/BCVAlso: Daclatasvir, Asunaprevir, BeclabuvirEach participant will each receive daclatasvir (30mg), asunaprevir (200mg) and beclabuvir (75mg) in a fixed-dose combination oral tablet for twice daily administration with food. | Drug | Hepatitis C treatment |
Primary outcome
Neurocognitive functioning
Time frame: 36 weeks
Mean change in neurocognitive functioning (global z-score representing overall neurocognitive performance across CogState, pegboard and colours trails)
Brain metabolite concentrations
Time frame: 36 weeks
Mean change in five absolute metabolite concentrations (NAA,Cho, Cr, mlo, glx)
8 secondary outcomes
Neurocognitive functioning
Time frame: 12 and 24 weeks
NAA metabolite concentration in the brain
Time frame: 12 and 24 weeks
Cho metabolite concentration in the brain
Time frame: 12 and 24 weeks
Cr metabolite concentration in the brain
Time frame: 12 and 24 weeks
MLO metabolite concentration in the brain
Time frame: 12 and 24 weeks
Glx metabolite concentration in the brain
Time frame: 12 and 24 weeks
Change in neurocognitive functioning compared between subjects with and without sustained virological response (SVR)
Time frame: 24 weeks
Change in brain metabolite concentrations compared between subjects with and without sustained virological response (SVR)
Time frame: 24 weeks
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Jun 2016.
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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.
Gregory Dore, BSc, MBBS, FRACP, MPH, PhD principal investigator
Kirby Institute
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing DCV/ASV/BCV in people with Hepatitis C, Chronic, run by Kirby Institute at 2 sites in Australia.
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 12 inclusion and 38 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: withdrawn, as of the sponsor's last update on 3 Jun 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Australia. 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
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 was withdrawn before enrolling participants, so there are no results.
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?
Neurocognitive functioning (time frame: 36 weeks). 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 3 Jun 2016.