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

Sponsoren

Hauptsponsor: Janssen Research & Development, LLC

Quelle Janssen Research & Development, LLC
Kurze Zusammenfassung

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.

Gesamtstatus Not yet recruiting
Anfangsdatum January 4, 2021
Fertigstellungstermin July 3, 2023
Primäres Abschlussdatum November 18, 2022
Phase Phase 2
Studientyp Interventional
Primärer Ausgang
Messen Zeitfenster
Change from Baseline in the Percentage of HBsAg Positive Hepatocytes at Week 40 Baseline and Week 40
Sekundäres Ergebnis
Messen Zeitfenster
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
Einschreibung 24
Bedingung
Intervention

Interventionsart: Drug

Interventionsname: JNJ-73763989

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

Interventionsart: Drug

Interventionsname: JNJ-56136379

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

Interventionsart: Drug

Interventionsname: Entecavir (ETV)

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

Interventionsart: Drug

Interventionsname: Tenofovir disoproxil

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

Interventionsart: Drug

Interventionsname: Tenofovir alafenamide (TAF)

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

Teilnahmeberechtigung

Kriterien:

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

Geschlecht: All

Mindestalter: 18 Years

Maximales Alter: 65 Years

Gesunde Freiwillige: No

Insgesamt offiziell
Nachname Rolle Zugehörigkeit
Janssen Research & Development, LLC Clinical Trial Study Director Janssen Research & Development, LLC
Gesamtkontakt

Nachname: Study Contact

Telefon: 844-434-4210

Email: [email protected]

Ort
Einrichtung:
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
Standort Länder

Belgium

Canada

France

Germany

Italy

New Zealand

Poland

United Kingdom

United States

Überprüfungsdatum

October 2020

Verantwortliche Partei

Art: Sponsor

Hat den Zugriff erweitert No
Bedingung Durchsuchen
Anzahl der Waffen 4
Armgruppe

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

Art: Experimental

Beschreibung: 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.

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

Art: Experimental

Beschreibung: 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.

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

Art: Experimental

Beschreibung: 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.

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

Art: Experimental

Beschreibung: 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.

Akronym INSIGHT
Patientendaten Yes
Studiendesign Info

Zuweisung: Randomized

Interventionsmodell: Parallel Assignment

Hauptzweck: Other

Maskierung: None (Open Label)

Quelle: ClinicalTrials.gov