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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT02292966




Registration number
NCT02292966
Ethics application status
Date submitted
25/09/2014
Date registered
18/11/2014
Date last updated
3/06/2016

Titles & IDs
Public title
Impact of HCV Treatment on Neurocognitive Functions and Brain Metabolism
Scientific 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
Secondary ID [1] 0 0
VHCRP1304
Universal Trial Number (UTN)
Trial acronym
HEPCOG-II
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Hepatitis C, Chronic 0 0
Condition category
Condition code
Infection 0 0 0 0
Other infectious diseases
Oral and Gastrointestinal 0 0 0 0
Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - DCV/ASV/BCV

Experimental: Hepatitis C treatment - 12 weeks of DCV/ASV/BCV therapy.


Treatment: Drugs: DCV/ASV/BCV
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.

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Neurocognitive functioning - Mean change in neurocognitive functioning (global z-score representing overall neurocognitive performance across CogState, pegboard and colours trails)
Timepoint [1] 0 0
36 weeks
Primary outcome [2] 0 0
Brain metabolite concentrations - Mean change in five absolute metabolite concentrations (NAA,Cho, Cr, mlo, glx)
Timepoint [2] 0 0
36 weeks
Secondary outcome [1] 0 0
Neurocognitive functioning - Mean change in neurocognitive functioning (global z-score representing overall neurocognitive performance across CogState, pegboard and colours trails)
Timepoint [1] 0 0
12 and 24 weeks
Secondary outcome [2] 0 0
NAA metabolite concentration in the brain
Timepoint [2] 0 0
12 and 24 weeks
Secondary outcome [3] 0 0
Cho metabolite concentration in the brain
Timepoint [3] 0 0
12 and 24 weeks
Secondary outcome [4] 0 0
Cr metabolite concentration in the brain
Timepoint [4] 0 0
12 and 24 weeks
Secondary outcome [5] 0 0
MLO metabolite concentration in the brain
Timepoint [5] 0 0
12 and 24 weeks
Secondary outcome [6] 0 0
Glx metabolite concentration in the brain
Timepoint [6] 0 0
12 and 24 weeks
Secondary outcome [7] 0 0
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)
Timepoint [7] 0 0
24 weeks
Secondary outcome [8] 0 0
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)
Timepoint [8] 0 0
24 weeks

Eligibility
Key inclusion criteria
- 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

- 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:

i. 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
Minimum age
18 Years
Maximum age
65 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
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

- 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

Study design
Purpose of the study
Treatment
Allocation to intervention
N/A
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 4
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Withdrawn
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 0 0
St Vincent's Hospital - Sydney
Recruitment hospital [2] 0 0
Westmead Hospital - Westmead
Recruitment postcode(s) [1] 0 0
2010 - Sydney
Recruitment postcode(s) [2] 0 0
2145 - Westmead

Funding & Sponsors
Primary sponsor type
Other
Name
Kirby Institute
Address
Country
Other collaborator category [1] 0 0
Commercial sector/Industry
Name [1] 0 0
Bristol-Myers Squibb
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief 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)). 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.
Trial website
https://clinicaltrials.gov/show/NCT02292966
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Gregory Dore, BSc, MBBS, FRACP, MPH, PhD
Address 0 0
The Kirby Institute, University of New South Wales
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT02292966