E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10008910 |
E.1.2 | Term | Chronic hepatitis B |
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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 single-dose pharmacokinetics of LDT600 in pediatric and adolescent patients (2-18 years of age) with chronic hepatitis B (CHB) infection • To evaluate the safety and tolerability of LDT600 in pediatric and adolescent patients with CHB infection
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E.2.2 | Secondary objectives of the trial | |
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Subjects or legal guardian must have read and signed the written informed consent form (ICF) after the nature of the study has been fully explained and all questions answered. • Subjects must be between the ages of 2 to 18 years with body weight within 15% of normal relative to age, based on either the Centers for Disease Control and Prevention (CDC) growth chart or national health service norms. • The subject must have documented HBV infection with both: - Positive HBsAg assay at Screening; - Positive serum HBV DNA at Screening • Subjects must have a screening creatinine clearance (CLcr) ≥ 80 mL/min/1.73 m2 as estimated by the Schwartz formula (See Section 8.2.2.1). • All female subjects of reproductive potential must have negative serum pregnancy test at Screening and negative urine pregnancy test on Day –1. • All subjects of reproductive potential must agree to use appropriate barrier method of birth control or agree to abstain from intercourse from Day –1 through Day 30 after dosing. • Subjects must agree not to take any other medications during the course of the study, without the approval of the Investigator, who in consultation with the Sponsor, may permit its use, on a case-by-case basis, when it is judged not to jeopardize the subject’s safety or interfere with study endpoints. • Subjects must agree not to consume alcohol within two days of reporting to the clinic on Day –1. |
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E.4 | Principal exclusion criteria |
• Decompensated liver disease (Child-Turcotte-Pugh (CTP) Score≥7, Class B and C) • Subjects with a positive Screening result for hepatitis C virus (HCV), hepatitis D virus (HDV), or HIV type 1 or 2 • Other clinically significant disease, condition or abnormality, unrelated to their HBV infection, as assessed by the Investigator, based on medical history, physical examination, 12-lead electrocardiogram (ECG), or clinical laboratory testing, including: - Hemoglobin value <110 g/L (11.0 g/dL) for males and <100 g/L (10.0 g/dL) for females - Absolute neutrophil count (ANC) <1,500/mm3 - Platelet count < 120,000/mm3 - White blood cell count (WBC) <3 x 109/L (<3,000/mm3) - Prothrombin time prolonged by more than 3 seconds, (based on the Upper Limit Normal [ULN]; of the reference value) - Serum amylase or lipase ≥1.5 x ULN; - Serum albumin <3.5 g/dL; - Total bilirubin ≥2.0 mg/dL; - AFP >50 ng/mL. - Serum ALT level >10 x ULN. - Blood urea nitrogen (BUN) within normal limits. • Participation in a clinical drug study within 30 days of Screening. • Treatment with interferon within six months of Screening. • Treatment with nucleoside/nucleotide reverse transcriptase inhibitors within three months of Screening. • Treatment with any other anti-HBV drugs or other antiviral therapy (e.g., acyclovir ganciclovir) within 30 days of study drug dosing. • Treatment with antibiotics within 7 days of Screening. • Females who are pregnant or are breast-feeding. • Subjects who are currently abusing alcohol or illicit drugs, or have a history of such abuse within the preceding two years. For the purposes of the present study, alcohol abuse is arbitrarily defined as frequent consumption of alcoholic beverages with an average daily intake of more than 40 g of alcohol.
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E.5 End points |
E.5.1 | Primary end point(s) |
• LDT600 plasma concentration and pharmacokinetic (PK) parameters of exposure (Cmax and AUC) • Incidence of adverse events (AEs) and serious adverse events (SAEs).
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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 | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | Yes |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | Yes |
E.7.1.3.1 | Other trial type description |
First administration in the paediatric population |
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E.7.2 | Therapeutic exploratory (Phase II) | No |
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 | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | No |
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 | No |
E.8.2.3 | Other | No |
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 | 5 |
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 | Information not present in EudraCT |
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 |
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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 | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 1 |