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.1.2 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 evaluate the steady-state pharmacokinetics (PK) and confirm age-appropriate dose of SOF/VEL/VOX FDC in pediatric subjects with chronic HCV infection
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E.2.2 | Secondary objectives of the trial |
To evaluate the safety and tolerability of SOF/VEL/VOX FDC in pediatric subjects with chronic HCV infection
To evaluate the antiviral efficacy of SOF/VEL/VOX FDC treatment in pediatric subjects with chronic HCV infection, as assessed by the proportion of pediatric subjects with sustained virological response (SVR) 12 weeks after cessation of treatment (SVR12)
To evaluate the antiviral efficacy SOF/VEL/VOX FDC treatment in pediatric subjects with chronic HCV infection, as assessed by the proportion of pediatric subjects with SVR 4 and 24 weeks after cessation of treatment (SVR4 and SVR24)
To evaluate the proportion of pediatric subjects with virologic failure, including on-treatment virologic failure and relapse
To evaluate the kinetics of circulating HCV RNA during treatment and after cessation of treatment
Please refer to protocol for full list of secondary objectives of the trial. |
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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 |
Pharmacogenomics substudy
To identify or validate genetic markers that may be predictive of the natural history of disease, response to therapy and/or tolerability of medical therapies through genetic discovery research (eg, pharmacogenomics), in subjects who provide their separate and specific consent |
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E.3 | Principal inclusion criteria |
1) Subject or parent/ legal guardian able to provide written informed consent prior to any screening evaluations. Willing to comply with study requirements in accordance with IEC/local requirements and the Investigator’s discretion. Subject will provide assent, if possible.
2) 3 to < 18 years of age as determined at Day 1
3) Chronic HCV infection (≥ 6 months) as documented by prior medical history or liver biopsy
4) HCV RNA ≥ 1000 IU/mL at Screening
5) Subjects must have a determination of prior treatment status as defined in protocol.
6) A negative serum pregnancy test is required at Screening and a negative urine test is required at Day 1 for female subjects of childbearing potential
7) Male subjects and female subjects of childbearing potential who engage in heterosexual intercourse must agree to use protocol specified method(s) of contraception
8) Lactating females must agree to discontinue nursing before the study drug is administered
9) Subject must be able to comply with the dosing instructions for study drug administration and be able to complete the study schedule of assessments. |
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E.4 | Principal exclusion criteria |
1) Current or prior history of clinical hepatic decompensation (eg, clinical ascites, encephalopathy, and/or variceal hemorrhage)
2) Any of the following laboratory parameters at Screening:
a) INR >1.2 x ULN
b) Platelets < 50,000/mm3
c) Albumin < 3.5 g/dL
d) ALT> 10 x ULN
e) AST > 10 x ULN
f) Direct bilirubin > 1.5 x ULN
g) Estimated glomerular filtration rate < 90 mL/min/1.73m2, as calculated by the Schwartz formula
3) Chronic liver disease of a non-HCV etiology (eg, hemochromatosis, Wilson’s disease, alpha-1 antitrypsin deficiency)
4) Evidence of hepatocellular carcinoma or other malignancy (with exception of certain resolved skin cancers)
5) Co-infection with human immunodeficiency virus (HIV), acute hepatitis A virus (HAV) or hepatitis B virus (HBV) (hepatitis B surface antigen [HBsAg] positive at Screening)
6) Current or prior history of any of the following:
a) Clinically significant illness (other than HCV) or any other major medical disorder that may have interfered with subject treatment, assessment, or compliance with the protocol; subjects currently under evaluation for a potentially clinically significant illness (other than HCV) are also excluded
b) Significant cardiac disease
c) Gastrointestinal malabsorption syndrome that may interfere with absorption of orally administered medications
d) History of solid organ or bone marrow transplantation
e) Psychiatric hospitalization, suicide attempt, and/or a period of disability as a result of their psychiatric illness within the last 5 years. Subjects with psychiatric illness (without the prior mentioned conditions) that is well controlled on a stable treatment regimen for at least 6 months prior to enrollment or has not required medication in the last 12 months may be included
7) Clinically relevant alcohol or drug abuse within 12 months of Screening. A positive drug screen will exclude subjects unless it can be explained by a prescribed medication; the diagnosis and prescription must be approved by the investigator
8) Use of any prohibited concomitant medications
9) Investigational agents taken within the past 28 days (except with the approval of the sponsor)
10) Known hypersensitivity to the study drug, the metabolites, or formulation excipients |
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E.5 End points |
E.5.1 | Primary end point(s) |
The appropriateness of the SOF/VEL/VOX FDC dose will be assessed by evaluating its steadystate PK. The primary PK endpoint is AUCtau of SOF, its major metabolite (GS-331007), VEL and VOX. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
12 weeks post last treatment dose |
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E.5.2 | Secondary end point(s) |
The secondary endpoints are:
1) Any AE leading to permanent discontinuation of study drug
2) The proportion of subjects with sustained virological response (SVR) 12 weeks after cessation of treatment (SVR12) is the key efficacy endpoint
3) The proportion of subjects with HCV RNA < LLOQ at 4 or 24 weeks after cessation of treatment (SVR4 and SVR24)
4) The proportion of subjects with virologic failure, including on-treatment virologic failure and relapse
5) The proportion of subjects with HCV RNA < LLOQ on treatment
6) Emergence of viral resistance to SOF, VEL, and VOX during treatment and treatment is discontinued
7) HCV RNA change from Day 1
8) Growth and development measurements including height and weight percentiles, Tanner Stage, radiographic bone age and two bone turn-over biochemical markers (CTX and P1NP)
9) Acceptability, including palatability, and swallowability assessments
10) Neuropsychiatric assessments as measured by PedsQL™ Pediatric Quality of Life survey |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Secondary efficacy endpoints will be assessed on treatment or at 12 and 24 weeks following discontinuation of treatment |
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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 | No |
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 | No |
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 | No |
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 | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 1 |
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 | 19 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
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 | 3 |
E.8.9.1 | In the Member State concerned months | 9 |
E.8.9.1 | In the Member State concerned days | 30 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 9 |
E.8.9.2 | In all countries concerned by the trial days | 30 |