E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Chronic Hepatitis C virus infection. |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Virus Diseases [C02] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10019744 |
E.1.2 | Term | Hepatitis C |
E.1.2 | System Organ Class | 10021881 - Infections and infestations |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
Evaluate efficacy, ie, sustained virologic response 12 weeks after the end of treatment (SVR12), of a combination treatment with AL-335, ODV, and SMV for 6 and 8 weeks in chronic HCV genotype 1, 2, 4, 5, or 6 infected subjects without cirrhosis
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E.2.2 | Secondary objectives of the trial |
• evaluate safety and tolerability, SVR4 and SVR24, on-treatment viral
kinetics, of a 6- and 8-week treatment regimen containing AL-335, ODV,
and SMV in subjects without cirrhosis
• evaluate incidence of on-treatment failure during treatment
• evaluate incidence of viral relapse after treatment
• assess changes from baseline in HCV NS3/4A, NS5A, and NS5B
sequence in subjects not achieving SVR,
• evaluate effect of the presence or absence of baseline HCV NS3/4A
polymorphisms (including Q80K), NS5A polymorphisms and/or NS5B
polymorphisms on treatment outcome
• evaluate concordance between SVR4, SVR12, and SVR24,
• evaluate PK of AL-335, ODV, SMV, and their metabolites in plasma,
• evaluate relationship between population-derived exposure
parameters of AL-335, ODV, and SMV with SVR12 and safety,
• explore impact of HCV and treatment with AL-335+ODV+SMV on the
Fatigue Severity Scale total score and 5-level EuroQol 5-Dimension
Visual Analog Scale score. |
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
• exploratory host DNA research related to SMV, ODV, AL-335 (and metabolites), or HCV infection.
• rich serial PK substudy, performed at selected study sites, rich serial PK blood sampling for the measurement of plasma concentrations of AL-335 (and its metabolites ALS-022227 and ALS-022399), SMV, and ODV will be performed in 20 subjects.
• sparse PK substudy, performed at selected sites, sparse PK sampling for AL-335 (and metabolites), SMV, and ODV will be performed for a subset of approximately 20 subjects who are not participating in the rich serial PK substudy.
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E.3 | Principal inclusion criteria |
• Documented chronic HCV infection: diagnosis of HCV infection >6
months before the first screening assessment, either by detectable HCV
RNA, an HCV positive antibody test or presence of histological changes
consistent with chronic hepatitis in a liver biopsy
• All subjects must have HCV genotype 1, 2, 4, 5 or 6 infection,
determined at screening
• HCV RNA plasma levels >10,000 IU/mL
• HCV treatment-naïve |
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E.4 | Principal exclusion criteria |
• Co-infection with multiple HCV genotypes
• Co-infection with HIV
• Presence of cirrhosis
• Prior exposure to an HCV DAA, either in combination with PegIFN or
IFN-free
• Any evidence of liver disease of non-HCV etiology
• Evidence of hepatic decompensation (history or current clinical
evidence of ascites, bleeding varices or hepatic encephalopathy)
• Subjects with HCV genotype 3 infection. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Percentage of Chronic HCV Infected Subjects who Achieve Sustained Virologic Response 12 weeks After the end of Treatment (EOT) (SVR12) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
12 weeks after the EOT (Week 6 or 8) |
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E.5.2 | Secondary end point(s) |
• Percentage of Subjects with Sustained Virologic Response at 4 (SVR4)
and 24 (SVR24) Weeks After EOT
• Percentage of Subjects With Viral Relapse During Follow-up up to 24
Weeks After EOT
• Percentage of Subjects With On-treatment Failure
• Percentage of Subjects With Virologic Response
• Time to Achieve Undetectable HCV RNA <LLOQ HCV RNA
• Effect of Presence or Absence of Baseline NS5A, NS5B or NS3/4A
Genes Polymorphisms on Treatment Outcome
• Changes from Baseline in Amino Acid Sequence in the HCV NS3/4A,
NS5A and NS5B Genes in Subjects, who did not Achieve SVR
• Change from Baseline Over Time in 5-level EuroQol 5 Dimension
(EQ5D5L) Visual Analog Scale (VAS) Score
• Change from Baseline Over Time in Fatigue Severity Scale (FSS) Total
Score
• Percentage of Subjects with Clinically Significant Positive or Negative
Change from Baseline in FSS Total and EQ5D5L VAS at Week 4, EOT
(Week 6 or 8), Follow up Week 4, 12 and 24
• Duration of Clinically Significant Positive or Negative Response from
Baseline in FSS Total and EQ5D5L VAS at Week 4, EOT (Week 6 or 8),
Follow up Week 4, 12 and 24
• Predose (trough) Plasma Concentration (C0h)
• Area Under the Curve From Time Zero to 24 Hours Postdose (AUC 24)
• Number of Subjects with Adverse Events (AEs) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Each secondary end point respectively:
• 4 and 24 weeks after EOT
• Up to Week 24 of follow-up
• Up to 6 or 8 weeks depending upon the Treatment received
• Up to 6 or 8 weeks (on-treatment)
• Up to 24 weeks of follow-up
• Baseline
• Baseline up to 24 weeks of follow-up
• Baseline up to 24 weeks of follow-up
• Baseline up to 24 weeks of follow-up
• Week 4, EOT, follow up Week 4, 12 and 24
• Week 4, EOT, follow up Week 4, 12 and 24
• Baseline (Day 1) up to EOT
• Baseline (Day 1) up to EOT
• Screening (Day 1) up to Week 38 (= Week 24 of Follow-up) |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | Yes |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
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E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 8 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 36 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Belgium |
Canada |
Germany |
Italy |
Poland |
Singapore |
Spain |
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E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 2 |
E.8.9.1 | In the Member State concerned days | 19 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 2 |
E.8.9.2 | In all countries concerned by the trial days | 19 |