E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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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 | 19.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10008910 |
E.1.2 | Term | Chronic hepatitis B |
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 |
The primary objective of the study is to evaluate HBsAg loss and seroconversion in subjects who stop tenofovir disoproxil fumarate (TDF) (Arm A) compared to subjects who continue TDF (Arm B)
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E.2.2 | Secondary objectives of the trial |
The secondary objectives of this study are:
• To characterize the restart of therapy in subjects who stop tenofovir disoproxil fumarate (TDF) (Arm A)
• To evaluate HBV DNA suppression (< 400 copies/mL) through Week 144
• To evaluate ALT flare (> ULN) through Week 144
• To evaluate subjects’ safety through laboratory tests, vital signs and adverse events reporting
We will also explore possible predictors of persistent virologic response.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Adult subjects greater than or equal to 18 years of age
HBeAg-negative at TDF therapy start
CHB, HBsAg positive, HBeAg-negative, anti-HBe positive
Received continuous TDF therapy treatment for at least 4 years prior to screening (i.e. TDF monotherapy or TDF + lamivudine or TDF + emtricitabine). If TDF has been used in combination with lamivudine or emtricitabine, lamivudine or emtricitabine must have been stopped at least 12 weeks prior to screening
Documented HBV DNA < 400 copies/mL for at least 3.5 years prior to screening
ALT within normal range
alpha-fetoprotein (AFP) less than or equal to 50 ng/mL
Calculated creatinine clearance greater than or equal to 70 mL/min
Less than than or equal to 10 kPa on Fibroscan assessment
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E.4 | Principal exclusion criteria |
• Known cirrhosis
• Evidence of fibrosis greater than or equal to Stage 3 (METAVIR) on liver biopsy or Fibroscan > 10 kPa within 6 months prior to screening
• History of decompensated liver disease (defined as direct [conjugated] bilirubin > 1.5 x ULN, PT > 1.5 x ULN, platelets < 75,000/mm³, serum albumin < 3.0 g/dL)
• history of clinical hepatic decompensation
• Evidence of hepatocellular carcinoma
• Serological evidence of coinfection with HIV, HCV, or hepatitis D infection (HDV)
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint is the proportion of subjects with HBsAg loss at Week 144 in both arms. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
HBsAg seroconversion is considered a secondary endpoint in supporting the primary objective, as seroconversion occurs following HBsAg loss.
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
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 | 14 |
E.8.5 | The trial involves multiple Member States | No |
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 | Information not present in EudraCT |
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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The last subject’s 30-day follow-up phone call or visit after Week 144 or after the early termination visit is defined as end of study |
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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 | 4 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 4 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |