A Study to Assess Intrahepatic and Peripheral Changes of Immunologic and Virologic Markers in Chronic Hepatitis B Virus Infection

A Phase 2 Randomized, Open-label, Parallel-group, Multicenter Study to Assess Intrahepatic and Peripheral Changes of Immunologic and Virologic Markers in Response to Combination Regimens Containing JNJ-73763989 and Nucleos(t)Ide Analog With or Without JNJ-56136379 in Patients With Chronic Hepatitis B Virus Infection

Patrocinadores

Patrocinador principal: Janssen Research & Development, LLC

Fuente Janssen Research & Development, LLC
Resumen breve

The purpose of this study is to assess changes in intrahepatic hepatitis B surface antigen (HBsAg) between baseline and on-treatment liver biopsy in response to JNJ-3989-based combination treatment.

Estado general Not yet recruiting
Fecha de inicio January 4, 2021
Fecha de Terminación July 3, 2023
Fecha de finalización primaria November 18, 2022
Fase Phase 2
Tipo de estudio Interventional
Resultado primario
Medida Periodo de tiempo
Change from Baseline in the Percentage of HBsAg Positive Hepatocytes at Week 40 Baseline and Week 40
Resultado secundario
Medida Periodo de tiempo
Change from Baseline in Intrahepatic Immune Response Baseline and Week 40
Change from Baseline in Intrahepatic Viral Parameters: HBsAg and HBV DNA Baseline up to Week 48
Change from Baseline in Intrahepatic cccDNA and pgRNA levels Baseline up to Week 48
Percentage of Participants with HBsAg Seroclearance at Week 72 Without Restarting Nucleos(t)ide Analog (NA)Treatment Week 72
Percentage of Participants with (Sustained) Reduction, Suppression, and/or Seroclearance Up to Week 96
Percentage of Participants with HBsAg and HBeAg Seroconversion Up to Week 96
Percentage of Participants with Flares Up to Week 96
Time to Achieve First HBsAg Seroclearance Up to Week 96
Percentage of Participants with Virologic Breakthrough Up to Week 48
Change from Baseline in HBV-specific Peripheral Blood T-cell Responses During the Study Intervention and Follow-up Phases Baseline up to Week 48
Percentage of participants with Adverse Events (AEs) and Serious AEs Up to Week 102
Percentage of Participants with Abnormalities in Clinical Laboratory Tests, Electrocardiogram (ECG), Vital Signs And Physical Examination Up to Week 96
Plasma concentration of JNJ-73763989 (JNJ-73763976 and JNJ-73763924), JNJ-56136379 and/or Nucleos(t)ide Analog (NA) Days 1, 29, 85, 169, 337
Inscripción 24
Condición
Intervención

Tipo de intervención: Drug

Nombre de intervención: JNJ-73763989

Descripción: JNJ-73763989 will be administered subcutaneously once every 4 weeks up to Week 44.

Tipo de intervención: Drug

Nombre de intervención: JNJ-56136379

Descripción: JNJ-56136379 tablets will be administered orally once daily up to 48 weeks.

Tipo de intervención: Drug

Nombre de intervención: Entecavir (ETV)

Descripción: ETV tablet will be administered orally once daily up to 48 weeks as NA treatment.

Tipo de intervención: Drug

Nombre de intervención: Tenofovir disoproxil

Descripción: Tenofovir disoproxil will be administered orally once daily up to 48 weeks as NA treatment.

Tipo de intervención: Drug

Nombre de intervención: Tenofovir alafenamide (TAF)

Descripción: TAF will be administered orally once daily up to 48 weeks as NA treatment.

Elegibilidad

Criterios:

Inclusion Criteria: - Medically stable on the basis of physical examination, medical history, vital signs, and triplicate 12-lead electrocardiogram (ECG) performed at screening - Hepatitis B virus (HBV) infection with documentation at least 6 months prior to screening: participants be either currently not treated with HBeAg positive status or virologically (nucleos[t]ide analog [NA]) suppressed with HBeAg negative status - Hepatitis B surface antigen (HBsAg) greater than (>) 100 International Units per Milliliter (IU/mL) at screening - Body mass index (BMI) between 18.0 and 35.0 kilogram per meter square (kg/m^2), extremes included - Highly effective contraceptive measures in place for female participants of childbearing potential or male participants with female partners of childbearing potential - Fibroscan liver stiffness measurement less than and equal to (<=) 9 Kilopascal (kPa) within 6 months prior to screening or at the time of screening Exclusion Criteria: - Evidence of infection with hepatitis A, C, D or E virus infection or evidence of human immunodeficiency, virus type 1 (HIV-1) or HIV-2 infection at screening - History or evidence of clinical signs/symptoms of hepatic decompensation including but not limited to: portal hypertension, ascites, hepatic encephalopathy, esophageal varices - History or signs of cirrhosis or portal hypertension, signs of hepatocellular carcinoma (HCC) or clinically relevant renal abnormalities on an abdominal ultrasound performed within 6 months prior to screening or at the time of screening - Presence of coagulopathy or bleeding disorder as indicated by: (a) International normalized ratio (INR) greater than or equal to (>=) 1.1* upper limit of normal (ULN); (b) Partial thromboplastin time >1.1*ULN; (c) Any signs of prolonged bleeding (>10 minutes) - Presence of hemoglobinopathy (including sickle cell disease, thalassemia) - Liver biopsy performed prior to screening that led to complications and that in the opinion of the investigator would prohibit another liver biopsy

Género: All

Edad mínima: 18 Years

Edad máxima: 65 Years

Voluntarios Saludables: No

Oficial general
Apellido Papel Afiliación
Janssen Research & Development, LLC Clinical Trial Study Director Janssen Research & Development, LLC
Contacto general

Apellido: Study Contact

Teléfono: 844-434-4210

Email: [email protected]

Ubicación
Instalaciones:
Johns Hopkins University | Baltimore, Maryland, 21287, United States
UZ Antwerpen | Edegem, 2650, Belgium
Toronto General Hospital | Toronto, ON M5G 2C4, Canada
Hôpital Beaujon | Clichy, 92110, France
University Medical Center | Hamburg, D-20246, Germany
Irccs Ospedale Maggiore Di Milano | Milano, 20122, Italy
Auckland Clinical Studies | Auckland, 1010, New Zealand
ID Clinic | Myslowice, 41-400, Poland
Kings College Hospital | London, SE5 9RF, United Kingdom
Ubicacion Paises

Belgium

Canada

France

Germany

Italy

New Zealand

Poland

United Kingdom

United States

Fecha de verificación

October 2020

Fiesta responsable

Tipo: Sponsor

Tiene acceso ampliado No
Condición Examinar
Número de brazos 4
Grupo de brazo

Etiqueta: Panel 1 Arm 1: JNJ-73763989+ JNJ-56136379+ NA

Tipo: Experimental

Descripción: Participants will receive JNJ-73763989 subcutaneous (SC) injection once every 4 weeks (last injection at Week 44) along with JNJ-56136379 tablet once daily and nucleos(t)ide analog (NA) treatment (either entecavir [ETV], tenofovir disoproxil or tenofovir alafenamide [TAF] tablets) once daily up to 48 weeks.

Etiqueta: Panel 1: Arm 2: JNJ-73763989 + NA

Tipo: Experimental

Descripción: Participants will receive JNJ-73763989 SC injection once every 4 weeks (last injection at Week 44) along with NA treatment (either ETV, tenofovir disoproxil or TAF tablets) once daily up to 48 weeks.

Etiqueta: Panel 2: Arm 1: JNJ-73763989+ JNJ-56136379+ NA

Tipo: Experimental

Descripción: Participants will receive JNJ-73763989 SC injection once every 4 weeks (last injection at Week 44) along with JNJ-56136379 tablet once daily and nucleos(t)ide analog (NA) treatment (ETV, tenofovir disoproxil or TAF tablets) once daily up to 48 weeks.

Etiqueta: Panel 2: Arm 2: JNJ-73763989 + NA

Tipo: Experimental

Descripción: Participants will receive JNJ-73763989 SC injection once every 4 weeks (last injection at Week 44) along with NA treatment (either ETV, tenofovir disoproxil or TAF tablets) once daily up to 48 weeks.

Acrónimo INSIGHT
Datos del paciente Yes
Información de diseño del estudio

Asignación: Randomized

Modelo de intervención: Parallel Assignment

Propósito primario: Other

Enmascaramiento: None (Open Label)

Fuente: ClinicalTrials.gov