E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Hepatitis B virus e-antigen (HBeAg)-negative subjects with chronic hepatitis B virus infection (CHB) |
Pacientes con infección crónica por el virus de la hepatitis B (HBC) HBeAg-negativo sin cirrosis |
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E.1.1.1 | Medical condition in easily understood language |
Subjects infected with hepatitis B virus |
Los sujetos infectados con el virus de la hepatitis B |
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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 | LLT |
E.1.2 | Classification code | 10054283 |
E.1.2 | Term | HBV DNA detectable |
E.1.2 | System Organ Class | 100000004848 |
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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 explore the anti-viral efficacy of combination therapy with ARB-001467 plus TDF and PEG-IFN α-2a in subjects with chronic hepatitis B (CHB) due to HBV genotype A or B, who are HBV-DNA positive |
Explorar la eficacia antiviral del tratamiento combinado con ARB-001467 más TDF y PEG-IFN α2a, en pacientes con hepatitis B crónica (HBC) por el virus del genotipo A o B que presentan ADN del VHB. |
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E.2.2 | Secondary objectives of the trial |
To evaluate the proportion of subjects who achieve HBsAg <lower limit of quantification (LLOQ) and who achieve HBV-DNA <LLOQ throughout the study
To evaluate on-treatment safety as measured by the frequency of adverse events (AEs), discontinuations due to AEs, and selected Grade 3-4 laboratory abnormalities (based on the Common Terminology Criteria for Adverse Events [CTCAE] criteria)
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Evaluar la proporción de pacientes que logran una concentración de HBsAg por debajo del límite inferior de cuantificación (LIC) y de ADN del VHB inferior al LIC a lo largo del estudio.
Evaluar la seguridad durante el tratamiento, determinada a través de la frecuencia de acontecimientos adversos (AA), las interrupciones del tratamiento debidas a AA y la incidencia de anomalías analíticas seleccionadas de grados 3-4 (sobre la base de los Criterios terminológicos comunes para acontecimientos adversos [Common Terminology Criteria for Adverse Events, CTCAE]). |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Chronic HBV infection as documented at screening by either:
a. Positive HBsAg, or hepatitis B virus e-antigen (HBeAg; negative or positive) or HBV-DNA at least 6 months prior to screening; OR
b. Historical liver biopsy consistent with chronic HBV infection with documentation available at screening
2. Subject must be HBV-DNA(+) with a HBV-DNA ≥1000 IU/mL and either treatment-naive or treatment-experienced, defined as follows:
a. Treatment naïve subjects: Subjects have never received nucleos(t)ide analogue (NA) therapies including, but not limited to, TDF, entecavir, telbivudine, or lamivudine and/or interferon-alpha; OR
b. Treatment experienced subjects: Subjects may have previously had NA therapies (including, but not limited to, TDF, entecavir, telbivudine, or lamivudine) and/or interferon-alpha therapy, but must have discontinued treatment at least 6 months prior to screening
3. Quantitative HBsAg ≥1000 IU/mL at the Screening Visit
4. HBV genotype A or B at the screening visit
5. Interleukin (IL)28B CC Genotype
6. HBeAg-negative at the screening visit
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1. Infección crónica por el VHB documentada en la selección de la siguiente manera:
a. HBsAg positivo, antígeno e del virus de la hepatitis B (HBeAg; negativo o positivo) o detección de ADN del VHB al menos 6 meses antes de la selección; b. biopsia hepática previa indicativa de infección crónica por el VHB con documentación disponible en la selección.
2. Presencia de ADN del VHB, con valores ≥1000 UI/ml y pacientes con o sin tratamiento previo, definidos de la siguiente manera:
a.Pacientes sin tratamiento previo: nunca han recibido tratamiento con análogos de nucleótidos o de nucleósidos (AN) como TDF, entecavir, telbivudina o lamivudina, ni con interferón α; O
b.Pacientes con tratamiento previo: pueden haber recibido anteriormente tratamiento con AN (entre otros, TDF, entecavir, telbivudina o lamivudina) o con interferón α, sin embargo, deben haber dejado de recibirlo al menos 6 meses antes de la selección.
3. HBsAg cuantitativo ≥1000 UI/ml en la visita de selección.
4. VHB de genotipo A o B en la visita de selección.
5. Interleucina (IL) 28B CC Genotipo
6. HBeAg negativo en la visita de selección.
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E.4 | Principal exclusion criteria |
1. Known co infection with any of the following: Human immunodeficiency virus (HIV), Hepatitis C virus (HCV), Hepatitis D virus (HDV), or Hepatitis E virus (HEV).
2. Any known pre existing medical or psychiatric condition that could interfere with the subject’s ability to provide informed consent or participate in study conduct, or that may confound study findings. |
1. Infección concomitante conocida con alguno de los siguientes: virus de la inmunodeficiencia humana (VIH), virus de la hepatitis C (VHC), virus de la hepatitis D (VHD), o virus de la hepatitis E (VHE).
2. Alguna enfermedad física o mental preexistente conocida que pudiera interferir en la capacidad del paciente para otorgar el consentimiento informado o participar en el estudio, o que pueda confundir los resultados de este. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Proportion of treated subjects with HBsAg decline ≥2 log10 |
Proporción de pacientes tratados que presenten una disminución del HBsAg ≥2 log10 |
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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) |
1) Proportion of subjects who achieve HBsAg <LLOQ and who achieve HBV-DNA <LLOQ
2)On-treatment safety as measured by frequency of AEs, discontinuations due to AEs, and selected Grade 3-4 laboratory abnormalities (including hematologic and liver function, based on CTCAE criteria) |
1) Proporción de pacientes con HBsAg < LIC y ADN del VHB < LIC
2) Seguridad durante el tratamiento, determinada a través de la frecuencia de AA, las interrupciones del tratamiento debidas a AA y la incidencia de anomalías analíticas seleccionadas de grados 3-4 (como las hematológicas y las funcionales hepáticas, sobre la base de los CTCAE). |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1) Weeks: 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28 and 30; and Post-treatment Weeks 4, 8, 12 and 24
2) Throughout course of study treatment up to 28 days after the last dose of study treatment. |
1) Semanas: 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28 y 30; Semanas 4, 8, 12 y 24 posteriores al tratamiento
2) Durante el curso del tratamiento del estudio hasta 28 días después de la última dosis del tratamiento del estudio. |
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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 | Yes |
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 | Yes |
E.6.13.1 | Other scope of the trial description |
Anti-viral activity |
Actividad anti-viral |
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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 | No |
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 | No |
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 | 6 |
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 |
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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 | 2 |
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 | 2 |