NCT02292966

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 Health

30
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Timeline
Completed

Started Jul 2015

Shorter than P25 for phase_4

Geographic Reach
1 country

2 active sites

Status
withdrawn

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

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Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

September 25, 2014

Completed
2 months until next milestone

First Posted

Study publicly available on registry

November 18, 2014

Completed
8 months until next milestone

Study Start

First participant enrolled

July 1, 2015

Completed
11 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

June 1, 2016

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

June 1, 2016

Completed
Last Updated

June 3, 2016

Status Verified

June 1, 2016

Enrollment Period

11 months

First QC Date

September 25, 2014

Last Update Submit

June 2, 2016

Conditions

Hepatitis C, Chronic

Keywords

Hepatitis CHepatitisAsunaprevirDaclatasvirBeclabuvirNeurocognitive functionBrain metabolitesDirect acting antiviral therapy

Outcome Measures

Primary Outcomes (2)

  • Neurocognitive functioning

    Mean change in neurocognitive functioning (global z-score representing overall neurocognitive performance across CogState, pegboard and colours trails)

    36 weeks

  • Brain metabolite concentrations

    Mean change in five absolute metabolite concentrations (NAA,Cho, Cr, mlo, glx)

    36 weeks

Secondary Outcomes (8)

  • Neurocognitive functioning

    12 and 24 weeks

  • NAA metabolite concentration in the brain

    12 and 24 weeks

  • Cho metabolite concentration in the brain

    12 and 24 weeks

  • Cr metabolite concentration in the brain

    12 and 24 weeks

  • MLO metabolite concentration in the brain

    12 and 24 weeks

  • +3 more secondary outcomes

Study Arms (1)

Hepatitis C treatment

EXPERIMENTAL

12 weeks of DCV/ASV/BCV therapy.

Drug: DCV/ASV/BCV

Interventions

DCV/ASV/BCVDRUG

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.

Also known as: Daclatasvir, Asunaprevir, Beclabuvir
Hepatitis C treatment

Eligibility Criteria

Age18 Years - 65 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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

You may not qualify if:

  • 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
  • +21 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (2)

St Vincent's Hospital

Sydney, New South Wales, 2010, Australia

Location

Westmead Hospital

Westmead, New South Wales, 2145, Australia

Location

MeSH Terms

Conditions

Hepatitis C, ChronicHepatitis CHepatitis

Interventions

daclatasvirasunaprevir8-cyclohexyl-N-((dimethylamino)sulfonyl)-1,1a,2,12b-tetrahydro-11-methoxy-1a-((3-methyl-3,8-diazabicyclo(3.2.1)oct-8-yl)carbonyl)cycloprop(d)indolo(2,1-a)(2)benzazepine-5-carboxamide

Condition Hierarchy (Ancestors)

Blood-Borne InfectionsCommunicable DiseasesInfectionsHepatitis, Viral, HumanVirus DiseasesFlaviviridae InfectionsRNA Virus InfectionsHepatitis, ChronicLiver DiseasesDigestive System DiseasesChronic DiseaseDisease AttributesPathologic ProcessesPathological Conditions, Signs and Symptoms

Study Officials

  • Gregory Dore, BSc, MBBS, FRACP, MPH, PhD

    Kirby Institute

    PRINCIPAL INVESTIGATOR
0

Study Design

Study Type
interventional
Phase
phase 4
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
OTHER GOV
Responsible Party
SPONSOR

Study Record Dates

First Submitted

September 25, 2014

First Posted

November 18, 2014

Study Start

July 1, 2015

Primary Completion

June 1, 2016

Study Completion

June 1, 2016

Last Updated

June 3, 2016

Record last verified: 2016-06

Locations

AU(2)