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 |
Chronic hepatitis C infection is infection with hepatitis C virus for more than 6 months |
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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 | 20.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10008912 |
E.1.2 | Term | Chronic 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 |
To compare the proportion of participants with undetectable hepatitis C virus load in their blood (HCV RNA less than the lower limit of quantification- LLOQ) at 12 weeks post-treatment (SVR12); following 8 weeks treatment with glecaprevir (300mg)/pibrentasvir (120mg); in people infected with hepatitis C without liver scarring (HCV treatment naïve non-cirrhosis chronic HCV patients), who have received a standard versus simplified schedule of safety and virological monitoring. |
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E.2.2 | Secondary objectives of the trial |
1. To compare the proportion of participants achieving SVR12 between those who received a standard versus simplified schedule of safety and virological monitoring based on modified intention to treat population. 2. To evaluate the proportion of participants who comply with treatment and study visits (both on-treatment compliance and early treatment discontinuation with be analysed). 3. To evaluate patient reported outcomes following treatment. 4. To evaluate safety and tolerability by monitoring adverse events during treatment. 5. To measure patient satisfaction on both arms. 6. To evaluate the prevalence and impact of baseline Resistance Associated Substitutions (RAS) on SVR12. 7. To evaluate cost-effectiveness of simplified monitoring. 8. To evaluate immunovirological factors associated with treatment clearance. 9. Exploratory Objective: - To measure the provider acceptability of the simplified monitoring strategy. |
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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 |
At selected sites peripheral blood mononuclear cells (PBMCs) will be collected at the time points specified in the protocol. These will be used for immunovirological research aims. Not all sites will participate in this sub-study as not all sites have the capacity and ability to process and store PBMCs. |
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E.3 | Principal inclusion criteria |
1) Have voluntarily signed the informed consent form. 2) 18 years of age or older. 3) Chronic HCV infection as defined by anti-HCV antibody or HCV RNA detection for greater than 6 months. 4) HCV RNA plasma ≥ 10,000 IU/ml at screening. 5) HCV genotype 1-6. 6) HCV treatment naïve (no prior treatment with an approved or investigation anti-HCV medication). 7) Stage F0-3, based on: hepatic elastography <12.5 kPa on Fibroscan® or APRI <1.0. 8) If co-infection with HIV is documented, the subject must meet the following criteria: - ART naïve with CD4 T cell count >500 cells/mm3; OR - On a stable ART regimen for >8 weeks prior to screening visit, with CD4 T cell count >200 cells/mm3 and a plasma HIV RNA level below the limit of detection. 9) Negative pregnancy test at screening and baseline (females of childbearing potential only). 10) All fertile females must be using effective contraception during treatment and during the 30 days after treatment end. |
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E.4 | Principal exclusion criteria |
1) History of any of the following: a. Clinically significant illness (other than HCV) or any other major medical disorder that may interfere with the participant treatment, assessment or compliance with the protocol; participants currently under evaluation for a potentially clinically significant illness (other than HCV) are also excluded. b. Clinical hepatic decompensation (i.e. ascites, encephalopathy or variceal haemorrhage). c. Solid organ transplant. d. History of severe, life-threatening or other significant sensitivity to any excipients of the study drugs. 2) Any of the following lab parameters at screening: a. ALT > 10 x ULN b. AST > 10 x ULN c. Direct bilirubin > ULN d. Platelets < 90,000/μL (cells/mm3) if Fibroscan® <12.5 kPa OR < 150,000/μL (cells/mm3) if Fibroscan® is unavailable and patient is included with APRI <1 e. Creatinine clearance (CLcr) < 50 mL/min f. Haemoglobin < 12g/dL for males; <11g/dL for females g. Albumin < LLN h. INR > 1.5 ULN unless subject has known haemophilia or is stable on an anticoagulant regimen affecting INR 3) Pregnant or breastfeeding female. 4) HBV infection (HBsAg positive). 5) Use of prohibited concomitant medications. 6) Chronic use of systemically administered immunosuppressive agents (e.g. prednisone equivalent > 10 mg/day for >2 weeks). 7) Therapy with any anti-neoplastic or immunomodulatory treatment (including supraphysiologic doses of steroids and radiation) ≤6 months prior to the first dose of study drug. 8) Any investigational drug ≤6 weeks prior to the first dose of study drug. 9) Ongoing severe psychiatric disease as judged by the treating physician. 10) Positive result of a urine drug screen at the Screening Visit for opiates, barbiturates, amphetamines, cocaine, benzodiazepines, phencyclidine, propoxyphene, or alcohol, with the exception of a positive result (including methadone) associated with documented short-term use or chronic stable use of a prescribed medication in that class. 11) Injecting drug use within the previous six months. 12) Inability or unwillingness to provide informed consent or abide by the requirements of the study. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Proportion of patients with undetectable HCV RNA based on ITT population. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
12 weeks post end of treatment (SVR12) |
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E.5.2 | Secondary end point(s) |
1) Proportion of patients with undetectable HCV RNA based on mITT population. 2) Proportion adherent to treatment and study visits (on-treatment adherence and early treatment discontinuation); 3) Change in health-related quality of life during treatment (measured by EG-5D-3L); 4) Resistance associated substitutions (RAS): SVR12 in participants with and without baseline RAS, and RAS distribution in participants with virological failures; 5) Patient treatment satisfaction measured by a questionnaire applied to all participants; EXPLORATORY ENDPOINT: 6) Provider acceptability of simplified monitoring strategy. SAFETY ENDPOINTS: 7) Proportion of patients with common adverse events (reported in greater than 5%). 8) Proportion of patients with at least one severe or potentially life threatening (grade 3 or 4) adverse event. 9) Proportion of patients with un-scheduled clinic visits. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1) SVR12 2) SVR12 3) SVR12 4) SVR12 5) SVR12 6) SVR12 7) SVR12 8) SVR12 9) SVR12 |
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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 | No |
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 | No |
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) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
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 |
Standard treatment monitoring schedule (standard of care) |
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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 | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 11 |
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 |
Australia |
Canada |
France |
Germany |
New Zealand |
Switzerland |
United Kingdom |
United States |
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E.8.7 | Trial has a data monitoring committee | Yes |
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 | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 1 |