Impact of HCV Treatment on Neurocognitive Functions and Brain Metabolism (HEPCOG-II)

Kirby Institute

Status and phase

Withdrawn

Phase 4

Conditions

Hepatitis C, Chronic

Treatments

Drug: DCV/ASV/BCV

Study type

Interventional

Funder types

Other

Industry

Identifiers

NCT02292966

VHCRP1304

Details and patient eligibility

About

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.

Full 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.

Sex

All

Ages

18 to 65 years old

Volunteers

No Healthy Volunteers

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

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