Clinical Trial Results:
A phase IV open-label, multicentre, international trial of paritaprevir/ritonavir, ombitasvir, dasabuvir with or without ribavirin for people with chronic hepatitis C virus genotype 1 infection and recent injection drug use or receiving opioid substitution therapy.
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Summary
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EudraCT number |
2015-003562-90 |
Trial protocol |
FR |
Global end of trial date |
31 Mar 2019
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Results information
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Results version number |
v1(current) |
This version publication date |
18 Dec 2019
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First version publication date |
18 Dec 2019
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Other versions |
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Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
VHCRP1405
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT02498015 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
University of New South Wales Sydney, The Kirby Institute
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Sponsor organisation address |
UNSW Sydney, Sydney, Australia, 2052
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Public contact |
Philippa Marks, University of New South Wales Sydney, The Kirby Institute, 61 0293850886, pmarks@kirby.unsw.edu.au
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Scientific contact |
Gregory Dore, University of New South Wales Sydney, The Kirby Institute, 61 0293850900, gdore@kirby.unsw.edu.au
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
14 Jun 2018
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Is this the analysis of the primary completion data? |
No
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Global end of trial reached? |
Yes
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Global end of trial date |
31 Mar 2019
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
The primary objective is to evaluate the proportion of patients with undetectable HCV RNA at 12 weeks post end of treatment (SVR12) following paritaprevir/ritonavir/ombitasvir, dasabuvir and ribavirin therapy for 12 weeks in people with chronic HCV genotype 1 infection and recent injection drug use or receiving opiate substitution therapy.
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Protection of trial subjects |
Treatment with paritaprevir/ritonavir, ombitasvir and dasabuvir with or without ribavirin has been shown to be more effective and less toxic that treatment with standard therapy. Clearing the virus significantly reduces the risk of future liver related morbidity and mortality which clearly outweighs the risk of mild or moderate reversible side effects while on treatment.
Patients were monitored closely for adverse events associated with blood collection and the treatment administration.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
30 Jun 2016
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Long term follow-up planned |
Yes
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Long term follow-up rationale |
Safety, Efficacy | ||
Long term follow-up duration |
3 Years | ||
Independent data monitoring committee (IDMC) involvement? |
Yes
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Australia: 5
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Country: Number of subjects enrolled |
Canada: 38
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Country: Number of subjects enrolled |
New Zealand: 13
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Country: Number of subjects enrolled |
Switzerland: 20
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Country: Number of subjects enrolled |
Norway: 4
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Country: Number of subjects enrolled |
France: 7
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Worldwide total number of subjects |
87
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EEA total number of subjects |
11
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
87
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From 65 to 84 years |
0
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85 years and over |
0
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Recruitment
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Recruitment details |
Subjects were recruited from 19 sites, in Australia (4 sites), Canada (6 sites), New Zealand (2 sites), Norway (1 site), Switzerland (4 sites), and France (2 sites). Subjects were recruited from people from 3 drug treatment clinics, 13 hospital clinics, 1 private practice, and 2 community clinics. | ||||||||||||||
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Pre-assignment
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Screening details |
Participants were 18 years or older, had chronic HCV genotype 1 (confirmed >6 months), had recently injected drugs (self-reported injecting drug use within 6 months of enrolment) or were receiving opioid substitution therapy. participants with HIV infection and/or decompensated liver disease were excluded. | ||||||||||||||
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Period 1
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Period 1 title |
Baseline
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Is this the baseline period? |
Yes | ||||||||||||||
Allocation method |
Non-randomised - controlled
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Blinding used |
Not blinded | ||||||||||||||
Blinding implementation details |
Not applicable, the study was open-label.
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Arms
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Arm title
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Single arm - open-label | ||||||||||||||
Arm description |
Subjects with HCV genotype 1b enrolled in the study received 2 tablets of co-formulated paritaprevir/ritonavir/ombitasvir (75 mg/50 mg/12.5 mg) once-daily, and 1 tablet of dasabuvir (250 mg) twice-daily administered orally for 12 weeks. Subjects with HCV genotype 1a also received ribavirin administered either 1000 mg or 1200 mg twice-daily according to body weight (<75 kg and >75 kg, respectively). Therapy was administered in weekly electronic blister packs for monitoring of adherence. | ||||||||||||||
Arm type |
Experimental | ||||||||||||||
Investigational medicinal product name |
ombitasvir/paritaprevir/ritonavir
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Investigational medicinal product code |
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Other name |
Viekirax
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
Patients received a fixed-dose combination of 2 tablets of the co-formulated paritaprevir/ritonavir/ombitasvir (75 mg/50 mg/12.5 mg) once-daily administered orally for 12 weeks.
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Investigational medicinal product name |
dasabuvir
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Investigational medicinal product code |
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Other name |
Exviera
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
Participants received 1 tablet of dasabuvir (250 mg) twice-daily administered orally for 12 weeks.
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Investigational medicinal product name |
ribavirin
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Investigational medicinal product code |
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Other name |
ribavirin
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
Ribavirin administered either 1000 mg or 1200 mg twice-daily according to body weight (<75 kg and >75 kg, respectively) orally for for 12 weeks.
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Period 2
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Period 2 title |
Primary endpoint SVR12
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Is this the baseline period? |
No | ||||||||||||||
Allocation method |
Non-randomised - controlled
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Blinding used |
Not blinded | ||||||||||||||
Blinding implementation details |
Not applicable, the study was open-label.
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Arms
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Arm title
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Single arm - open-label | ||||||||||||||
Arm description |
Subjects with HCV genotype 1b enrolled in the study received 2 tablets of co-formulated paritaprevir/ritonavir/ombitasvir (75 mg/50 mg/12.5 mg) once-daily, and 1 tablet of dasabuvir (250 mg) twice-daily administered orally for 12 weeks. Subjects with HCV genotype 1a also received ribavirin administered either 1000 mg or 1200 mg twice-daily according to body weight (<75 kg and >75 kg, respectively). Therapy was administered in weekly electronic blister packs for monitoring of adherence. | ||||||||||||||
Arm type |
Experimental | ||||||||||||||
Investigational medicinal product name |
ombitasvir/paritaprevir/ritonavir
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Investigational medicinal product code |
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Other name |
Viekirax
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
Patients received a fixed-dose combination of 2 tablets of the co-formulated paritaprevir/ritonavir/ombitasvir (75 mg/50 mg/12.5 mg) once-daily administered orally for 12 weeks.
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Investigational medicinal product name |
dasabuvir
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Investigational medicinal product code |
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Other name |
Exviera
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
Participants received 1 tablet of dasabuvir (250 mg) twice-daily administered orally for 12 weeks.
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Investigational medicinal product name |
ribavirin
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Investigational medicinal product code |
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Other name |
ribavirin
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
Ribavirin administered either 1000 mg or 1200 mg twice-daily according to body weight (<75 kg and >75 kg, respectively) orally for for 12 weeks.
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Baseline characteristics reporting groups
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Reporting group title |
Single arm - open-label
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Reporting group description |
Subjects with HCV genotype 1b enrolled in the study received 2 tablets of co-formulated paritaprevir/ritonavir/ombitasvir (75 mg/50 mg/12.5 mg) once-daily, and 1 tablet of dasabuvir (250 mg) twice-daily administered orally for 12 weeks. Subjects with HCV genotype 1a also received ribavirin administered either 1000 mg or 1200 mg twice-daily according to body weight (<75 kg and >75 kg, respectively). Therapy was administered in weekly electronic blister packs for monitoring of adherence. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Single arm - open-label
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Reporting group description |
Subjects with HCV genotype 1b enrolled in the study received 2 tablets of co-formulated paritaprevir/ritonavir/ombitasvir (75 mg/50 mg/12.5 mg) once-daily, and 1 tablet of dasabuvir (250 mg) twice-daily administered orally for 12 weeks. Subjects with HCV genotype 1a also received ribavirin administered either 1000 mg or 1200 mg twice-daily according to body weight (<75 kg and >75 kg, respectively). Therapy was administered in weekly electronic blister packs for monitoring of adherence. | ||
Reporting group title |
Single arm - open-label
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Reporting group description |
Subjects with HCV genotype 1b enrolled in the study received 2 tablets of co-formulated paritaprevir/ritonavir/ombitasvir (75 mg/50 mg/12.5 mg) once-daily, and 1 tablet of dasabuvir (250 mg) twice-daily administered orally for 12 weeks. Subjects with HCV genotype 1a also received ribavirin administered either 1000 mg or 1200 mg twice-daily according to body weight (<75 kg and >75 kg, respectively). Therapy was administered in weekly electronic blister packs for monitoring of adherence. | ||
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End point title |
SVR12 | |||||||||
End point description |
The primary efficacy endpoint was the proportion of participants with SVR12, which was defined as a HCV RNA load below the limit of quantification 12 weeks after the end of treatment in all participants who received at least one dose of study medication (ITT).
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End point type |
Primary
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End point timeframe |
12 weeks post-treatment
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Statistical analysis title |
Intention to treat | |||||||||
Comparison groups |
Single arm - open-label v Single arm - open-label
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Number of subjects included in analysis |
164
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Analysis specification |
Pre-specified
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Analysis type |
other | |||||||||
P-value |
< 0.05 | |||||||||
Method |
t-test, 2-sided | |||||||||
Parameter type |
Mean difference (final values) | |||||||||
Point estimate |
90
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Confidence interval |
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level |
95% | |||||||||
sides |
2-sided
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lower limit |
82 | |||||||||
upper limit |
95 | |||||||||
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Adverse events information
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Timeframe for reporting adverse events |
Treatment emergent adverse events up to 28 days after last dose of study treatment
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
18.1
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Reporting groups
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Reporting group title |
Single arm - open-label
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Reporting group description |
The study was open-label. Subjects enrolled in the study received 12 weeks of paritaprevir/ritonavir, ombitasvir, dasabuvir with (G1a) or without (G1b) ribavirin in an oral twice-daily fixed dose combination. Therapy was administered in weekly electronic blister packs for monitoring of adherence. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? No | |||
Interruptions (globally) |
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| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| Enrolment closed prematurely at 87/100 due to slower than anticipated recruitment. Participants were recruited from tertiary hospital HCV clinics, drug treatment clinics and community health centres experienced in HCV care in PWID and/or on OST. | |||
Online references |
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| http://www.ncbi.nlm.nih.gov/pubmed/30384028 |
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