Clinical Trial Results:
A Multicenter, Open-Label Study to Evaluate the Efficacy and Safety of Glecaprevir/Pibrentasvir in Renally-Impaired Adults with Chronic Hepatitis C Virus Genotype 1 – 6 Infection (EXPEDITION-5)
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Summary
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EudraCT number |
2016-004182-60 |
Trial protocol |
SE ES DE PL GR IT |
Global end of trial date |
05 Jun 2018
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Results information
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Results version number |
v1(current) |
This version publication date |
22 Feb 2019
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First version publication date |
22 Feb 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 |
M16-127
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT03069365 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
AbbVie Deutschland GmbH & Co. KG
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Sponsor organisation address |
AbbVie House, Vanwall Business Park, Vanwall Road, Maidenhead, Berkshire, United Kingdom, SL6-4UB
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Public contact |
Global Medical Services
, AbbVie, 001 800-633-9110,
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Scientific contact |
Neddie Zadeikis, AbbVie, neddie.zadeikis@abbvie.com
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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 |
05 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 |
05 Jun 2018
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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 |
This was a Phase 3b, open-label, non-randomized, multicenter study to evaluate the efficacy and safety of glecaprevir/pibrentasvir (GLE/PIB) in participants with chronic hepatitis C virus (HCV) genotype (GT) 1 – 6 infection without liver cirrhosis or with compensated liver cirrhosis and with chronic renal impairment in participants who were either HCV treatment-naïve (TN) or prior treatment-experienced (TE) with interferon (IFN) or pegylated interferon (PegIFN) with or without ribavirin (RBV), or sofosbuvir (SOF) plus RBV with or without pegIFN. The study included a 42-day screening period, a treatment period of either 8, 12, or 16 weeks, and a 24-week post-treatment period. The duration of treatment was determined by product labeling.
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Protection of trial subjects |
Prior to the initiation of any screening or study-specific procedures, the investigator or his or her representative explained the nature of the study to the subject or his or her representative and answered all questions regarding this study.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
28 Mar 2017
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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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 |
Canada: 4
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Country: Number of subjects enrolled |
Germany: 11
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Country: Number of subjects enrolled |
Greece: 6
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Country: Number of subjects enrolled |
Italy: 17
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Country: Number of subjects enrolled |
Korea, Republic of: 11
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Country: Number of subjects enrolled |
Poland: 8
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Country: Number of subjects enrolled |
Puerto Rico: 5
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Country: Number of subjects enrolled |
Spain: 7
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Country: Number of subjects enrolled |
Sweden: 4
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Country: Number of subjects enrolled |
United States: 28
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Worldwide total number of subjects |
101
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EEA total number of subjects |
53
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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) |
71
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From 65 to 84 years |
29
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85 years and over |
1
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Recruitment
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Recruitment details |
The study enrollment was monitored to meet the following non-mutually exclusive enrollment criteria: (1) up to approximately 40 subjects with Stage 3b chronic kidney disease (CKD), (2) up to approximately 75 hepatitis C virus genotype 1 (HCV GT1)-infected subjects, (3) up to approximately 30 subjects with compensated cirrhosis. | ||||||||||
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Pre-assignment
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Screening details |
Subjects were HCV treatment-naive (no prior dose of any approved or investigational regimen) or treatment-experienced HCV genotype 1 – 6-infected adult male and female subjects with or without compensated cirrhosis, who had CKD Stage 3b, 4, or 5. Subjects had up to 42 days after the Screening Visit to confirm eligibility and enroll into the study. | ||||||||||
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Period 1
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Period 1 title |
Overall trial (overall period)
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Is this the baseline period? |
Yes | ||||||||||
Allocation method |
Non-randomised - controlled
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Blinding used |
Not blinded | ||||||||||
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Arms
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Arm title
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GLE/PIB for 8, 12, or 16 weeks | ||||||||||
Arm description |
HCV genotype 1,2,4-6 non-cirrhotic, treatment-naive or treatment-experienced; genotype 3 non-cirrhotic, treatment-naïve participants treated with glecaprevir/pibrentasvir (GLE/PIB)- three 100 mg/40 mg co-formulated tablets once daily with food for 8 weeks; HCV genotype 1,2,4-6 compensated cirrhosis, treatment-naive or treatment-experienced; genotype 3 compensated cirrhosis, treatment-naïve participants treated with glecaprevir/pibrentasvir (GLE/PIB)- three 100 mg/40 mg co-formulated tablets once daily with food for 12 weeks; HCV genotype 3 non-cirrhotic or with compensated cirrhosis, treatment-experienced participants treated with glecaprevir/pibrentasvir (GLE/PIB)- three 100 mg/40 mg co-formulated tablets once daily with food for 16 weeks | ||||||||||
Arm type |
Experimental | ||||||||||
Investigational medicinal product name |
Glecaprevir/pibrentasvir
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Investigational medicinal product code |
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Other name |
ABT-493/ABT-530, MAVYRET
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Pharmaceutical forms |
Film-coated tablet
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Routes of administration |
Oral use
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Dosage and administration details |
Three 100 mg/40 mg co-formulated tablets once daily with food for 8, 12, or 16 weeks
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Baseline characteristics reporting groups
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Reporting group title |
GLE/PIB for 8, 12, or 16 weeks
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Reporting group description |
HCV genotype 1,2,4-6 non-cirrhotic, treatment-naive or treatment-experienced; genotype 3 non-cirrhotic, treatment-naïve participants treated with glecaprevir/pibrentasvir (GLE/PIB)- three 100 mg/40 mg co-formulated tablets once daily with food for 8 weeks; HCV genotype 1,2,4-6 compensated cirrhosis, treatment-naive or treatment-experienced; genotype 3 compensated cirrhosis, treatment-naïve participants treated with glecaprevir/pibrentasvir (GLE/PIB)- three 100 mg/40 mg co-formulated tablets once daily with food for 12 weeks; HCV genotype 3 non-cirrhotic or with compensated cirrhosis, treatment-experienced participants treated with glecaprevir/pibrentasvir (GLE/PIB)- three 100 mg/40 mg co-formulated tablets once daily with food for 16 weeks | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
GLE/PIB for 8, 12, or 16 weeks
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Reporting group description |
HCV genotype 1,2,4-6 non-cirrhotic, treatment-naive or treatment-experienced; genotype 3 non-cirrhotic, treatment-naïve participants treated with glecaprevir/pibrentasvir (GLE/PIB)- three 100 mg/40 mg co-formulated tablets once daily with food for 8 weeks; HCV genotype 1,2,4-6 compensated cirrhosis, treatment-naive or treatment-experienced; genotype 3 compensated cirrhosis, treatment-naïve participants treated with glecaprevir/pibrentasvir (GLE/PIB)- three 100 mg/40 mg co-formulated tablets once daily with food for 12 weeks; HCV genotype 3 non-cirrhotic or with compensated cirrhosis, treatment-experienced participants treated with glecaprevir/pibrentasvir (GLE/PIB)- three 100 mg/40 mg co-formulated tablets once daily with food for 16 weeks | ||
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End point title |
Percentage of Participants Achieving Sustained Virologic Response 12 Weeks Post Dosing (SVR12) [1] | ||||||||
End point description |
SVR12 was defined as hepatitis C virus ribonucleic acid (HCV RNA) level less than the lower limit of quantification (LLOQ) 12 weeks after the last actual dose of study drug. Participants with missing data after backwards imputation were counted as non-responders.
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End point type |
Primary
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End point timeframe |
12 weeks after the last actual dose of study drug
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| Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Statistical analyses were not performed for this endpoint. |
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| Notes [2] - Intent to treat population: all participants who received at least 1 dose of study drug |
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| No statistical analyses for this end point | |||||||||
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End point title |
Percentage of Participants With On-treatment Virologic Failure | ||||||||
End point description |
On-treatment virologic failure was defined as:
• Confirmed increase from nadir in hepatitis C virus ribonucleic acid (HCV RNA) defined as confirmed increase of >
1 log (subscript)10(subscript) IU/mL above nadir during treatment; or
• Confirmed HCV RNA greater than or equal to 100 IU/mL after HCV RNA less than the lower limit of quantification (LLOQ) during study drug treatment; or
• HCV RNA ≥ LLOQ at the end of treatment with at least 6 weeks of treatment
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End point type |
Secondary
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End point timeframe |
Up to 16 weeks
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| Notes [3] - Intent to treat population: all participants who received at least 1 dose of study drug |
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| No statistical analyses for this end point | |||||||||
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End point title |
Percentage of Participants With Post-treatment Relapse | ||||||||
End point description |
Post-treatment relapse was defined as confirmed hepatitis C virus ribonucleic acid (HCV RNA) ≥ the lower limit of quantification (LLOQ) between the end of treatment and 12 weeks after the last dose of study drug among participants who completed treatment as planned with HCV RNA < LLOQ at the end of treatment and had post-treatment HCV RNA data; participants who had been shown to be reinfected were not considered to have relapsed.
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End point type |
Secondary
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End point timeframe |
Up to 12 weeks after the last dose of study drug
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| Notes [4] - Subjects rcvd ≥ 1 dose of drug, completed Tx, HCV RNA < LLOQ at last Tx, ≥ 1 post-Tx HCV RNA value |
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| No statistical analyses for this end point | |||||||||
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Adverse events information
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Timeframe for reporting adverse events |
Treatment-emergent adverse events (TEAEs) and serious adverse events (TESAEs) were collected from the time of study drug administration until 30 days after the last dose of study drug (up to 20 weeks).
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Adverse event reporting additional description |
TEAEs and TESAEs are defined as any adverse event (AE) with an onset date that is after the first dose of study drug until 30 days after the last dose of study drug and were collected whether elicited or spontaneously reported by the participant.
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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 |
21.0
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Reporting groups
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Reporting group title |
GLE/PIB for 8, 12, or 16 Weeks
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Reporting group description |
Glecaprevir/pibrentasvir (GLE/PIB): three 100 mg/40 mg co-formulated tablets once daily with food | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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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? Yes | |||
Date |
Amendment |
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20 Jan 2017 |
Amendment 1
• Removed the lab test soluble erythropoietin receptor (sEpoR)
• Clarified the timing and process around distributing the dosing card to subjects
• Removed hepatitis B surface antigen (HbsAg) testing from Day 1
• Removed the word "separate" from the Subject Information and Consent section as the optional pharmacogenetic informed consent form (ICF) may have been included in the Main ICF
• Corrected an administrative error to show that Study Drug would not be dispensed at Screening, but instead at Day 1, and that study drug accountability and review of study drug adherence would not occur at Screening; clarified that Hepatitis C testing would occur at Screening as well as Hepatitis B and HIV testing; removed HBsAg testing on Day 1.
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27 Jul 2017 |
Amendment 2
• Updated the method for the calculation of the two-sided 95% CI for the primary efficacy endpoint to use the normal approximation to the binomial distribution, unless the number of SVR12 non-responders was less than 5, where the Wilson score method would be used
• Clarified that all prohibited medications had to be discontinued 14 days or 10 half-lives prior to initiating GLE/PIB and could be resumed 14 days after last dose of study drug
• Clarified that any historical presence of hepatocellular carcinoma (HCC) was exclusionary; also clarified that prior or current empiric use of lactulose/rifaximin for neurologic indications was exclusionary
• Clarified the Screening procedures for HCC in the Screening period, treatment period, and post-treatment period
• Clarified when protocol deviations were to be reported to regulatory authorities
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30 Jan 2018 |
Amendment 3
• Clarified that serum samples for tumor necrosis factor-alpha (TNF-α) would not be collected and analyzed. Instead, the Archive Plasma samples collected throughout the study would be analyzed for TNF-α
• Corrected analyses of the signature amino acid position of HCV GT3
• Clarified that Hematology/Chemistry/Coagulation would only be performed if the subject discontinued prior to post-treatment Week 4 unless the patient was cirrhotic, in which case labs were to be collected to test international normalized ratio (INR), total bilirubin, and albumin in the post-treatment period
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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. | |||
| None reported | |||
