Hepatitis C Infection (HCV) (genotype 1a/1b/4) MedDRA version: 20.0 Level: PT Classification code 10008912 Term: Chronic hepatitis C System Organ Class: 10021881 - Infections and infestations
Conditions
Interventions
Trade Name: Viekirax
Product Name: Viekirax
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Ombitasvir
Concentration unit:
Sponsors
Imperial College London
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Aged =18 years 2. Infected with HCV genotype 1a or 1b or 4 with access to first-line treatment appropriate for their genotype (ombitasvir/paritaprevir/(dasabuvir)/ritonavir or glecaprevir/pibrentasvir) 3. At least one detectable viremia 6 months prior to randomisation (by quantitative HCV RNA, qualitative assay or HCV genotype), with no intervening undetectable results 4. Plasma HCV RNA >LLOQ at screening 5. No evidence of significant liver fibrosis resulting from any aetiology (defined as Fibroscan* score =7.1kPa, equivalent to F0-F140, within 180 days prior to planned randomisation or biopsy consistent with mild fibrosis (Ishak score =18kg/m2 7. Laboratory tests: platelets >=60x109/l, haemoglobin >12g/dl (male) or >11g/dl (female), creatinine clearance (estimated using Cockcroft-Gault) >=60ml/min, international normalised ratio (INR) 24 weeks at the screening visit. Are the trial subjects under 18? no Number of subjects for this age range: 0 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 0 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range 0
Exclusion criteria
Exclusion criteria: 1. Previous DAA exposure for this infection (previous treatment with pegylated-interferon and/or ribavirin allowed. DAA treatment for a previously cured infection allowed). 2. FEMALES ONLY: Lactating, or pregnant, or planning to become pregnant, or not willing to use effective contraception, during the study and for four months after last dose of study medication. 3. FEMALES ONLY: currently taking ethinyl-oestradiol-containing medicinal products such as those contained in most combined oral contraceptives or contraceptive vaginal rings. 4. MALES only: planning pregnancy with female partner, or not willing to use effective contraception, during the study and for seven months after last dose of study medication. 5. Malignancy within 5 years prior to screening 6. Any condition in the judgement of the investigator which might limit the patient’s life expectancy 7. Currently receiving medication know to interact with study medication (ombitasvir, paritaprevir, dasabuvir, ritonavir, sofosbuvir, ledipasvir, ribavirin, glecaprevir, pibrentasvir; see relevant prescribing information9,10,16,39, Sections 5.3.4, 5.4.4, 5.5.4 and 5.6.4 below, and www.hep-druginteractions.org) 8. Disorder which may cause ongoing liver disease including, but not limited to, active hepatitis B, ongoing alcohol misuse 9. Any disorder which in the opinion of the investigator may have a significant negative impact on the ability of the patient to adhere to the trial regimen 10. Use of other investigational products within 60 days of screening 11. Known hypersensitivity to any active ingredient and/or excipients of the study medicines, namely Microcrystalline cellulose, Lactose monohydrate, Croscarmellose sodium, Magnesium stearate, Gelatine, Shellac, Propylene glycol, Polyethylene glycol, Ammonium hydroxide, Pregelatinised maize starch, Sodium starch glycolate (type A), Maize starch, Hypromellose, Talc, Ethylcellulose aqueous dispersion, Triacetin, Copovidone, Colloidal anhydrous silica, vitamin E (tocopherol) polyethlyene glycol succinate, sodium stearyl fumarate, Polyvinyl alcohol, Macrogol 3350, Sunset yellow FCF aluminium lake (E110), Colouring agent (E132), Titanium dioxide (E171), Yellow iron oxide (E172), Red iron oxide (E172), Black iron oxide (E172). 12. History of severe pre-existing cardiac disease, including unstable or uncontrolled cardiac disease, in the previous six months 13. Haemoglobinopathies (e.g., thalassemia, sickle-cell anaemia).
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: 1)To evaluate if short course HCV first line treatment (duration based on the viral load in the blood) followed by 12 weeks re-treatment of those failing therapy is non-inferior to a fixed duration of 8 weeks first line treatment followed by 12 weeks re-treatment of those failing therapy, looking at overall HCV cure in patients with minimal fibrosis and chronic HCV (type 1 and 4) infection. 2)To test the benefits and risks of adding adjunctive ribavirin with 4-8 weeks first line therapy. ; Secondary Objective: To test whether re-treatment with 12 weeks treatment after failure of first line therapy still achieves cure in the majority of the small proportion failing short-course first line. To explore whether factors other than baseline HCV viral load influence and therefore better predict the response to a) short course combined direct acting antivirals (DAA) and b) re-treatment. Factors explored will include the virus characteristics in addition to the factors relating to individuals infected such as age, body mass index and human genetic variation. Factors relating to the immune system will also be assessed ; Primary end point(s): The primary outcome for the biomarker-stratified duration comparison is the proportion of patients in each randomised group who achieve Sustained Virological Response 12 weeks after treatment (SVR12). SVR12 is defined as undetectable plasma (HCV RNA LLOQ (taken at least 1 week apart) after two consecutive visits with HCV RNA 1 log10 increase above HCV RNA nadir on treatment to a value >2000 copies/ml For the Ribavirin comparison, the primary outcome is the proportion of patients in each randomised group who achieve SVR12 following first line treatment, assessed 12 weeks after the end of treatment. ; Timepoint(s) of evaluation of this end point: The study is planned to re | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - SVR12 after first-line treatment (where not the primary outcome) - SVR12 after the end of the combined first and any re-treatment phases (where not the primary outcome) - SVR24 after the end of the combined first and any re-treatment phases - SVR24 after first-line treatment only - Lack of initial virological response - Viral load rebound after becoming undetectable - Serious adverse events - Grade 3/4 adverse events - Grade 3/4 adverse events judged definitely/probably related to interventions - Treatment-modifying adverse events (any grade) - Grade 3/4 anaemia - Emergence of resistance-associated HCV variants - Sensitivity/specificity of point–of-care diagnostic for IL28 - Costs and cost-effectiveness ;Timepoint(s) of evaluation of this end point: The study is planned to recruit over 2 years, patients will be followed for 24 weeks post end of first line treatment, if they fail first line they will receive another 12 weeks of retreatment and be followed for another 24 weeks post end of treatment. Analysis of the endpoints will be conducted after all participants have completed their follow-up. | — |
Countries
United Kingdom
Contacts
Public ContactEmily Dennis
MRC CTU at UCL, Institute of Clinical Trials and Methodology
Outcome results
None listed