A Study of JNJ 73763989+JNJ 56136379+Nucleos(t)Ide Analog (NA) Regimen Compared to NA Alone in e Antigen Negative Virologically Suppressed Participants With Chronic Hepatitis B Virus Infection

Hepatitis B, Chronic Clinical Trial

Official title:

A Randomized, Double Blind, Placebo-controlled Phase 2b Study to Evaluate Efficacy, Pharmacokinetics, and Safety of 48-week Study Intervention With JNJ 73763989+JNJ 56136379+Nucleos(t)Ide Analog (NA) Regimen Compared to NA Alone in e Antigen Negative Virologically Suppressed Participants With Chronic Hepatitis B Virus Infection

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04288310
• Other study ID #: CR108679
• Secondary ID: 73763989PAHPB200
• Status: Recruiting
• Phase: Phase 2
• Start date: November 6, 2019
• Est. completion date: February 18, 2022

Study information

• Verified date: February 2020
• Source: Janssen Sciences Ireland UC
• Contact: Study Contact
• Phone: 844-434-4210
• Email: JNJ.CT[@]sylogent.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to evaluate the efficacy of 48-week study intervention with JNJ-73763989+JNJ-56136379+nucleos(t)ide analog (NA) regimen compared to NA alone assessed by HBsAg levels. This study is part of HepB Wings Platform Trial (PLATFORMPAHPB2001).

Description:

Hepatitis B virus (HBV) is a small deoxyribonucleic acid (DNA) virus that infects the liver and can cause either acute or chronic infection. It consists of a so-called nucleocapsid in which viral DNA is packed with hepatitis B core protein (HBc) and membranous envelope containing hepatitis B surface antigen (HBsAg). Chronic HBV infection may lead to serious illnesses like cirrhosis and hepatocellular carcinoma (HCC). Oral treatment with NAs is effective at suppressing viral DNA formation and lowering virus concentration in blood to levels below lower limit of quantification (LLOQ). JNJ-73763989 is a liver-targeted antiviral therapeutic for subcutaneous injection designed to treat chronic HBV infection via ribonucleic acid interference mechanism but rarely lead to functional cure defined as sustained loss of HBs Ag and HBV DNA in serum. JNJ-56136379 is an orally administered capsid assembly modulator that is being developed for treatment of chronic HBV infection. The aim of study is to evaluate efficacy of 48-week study intervention with JNJ-3989+JNJ-6379+NA regimen compared to NA alone, assessed by HBsAg seroclearance at Week 72 (i.e., 24 weeks after completion of all study interventions at Week 48) without restarting NA treatment in HBeAg negative virologically suppressed chronic hepatitis B (CHB) infected participants who received NA treatment for at least 2 years prior to screening. The study will be 2.3 years and will be conducted in 3 phases: a screening phase (4 weeks), a study intervention phase (48 weeks), and a follow-up phase (48 weeks). Safety will be evaluated by AEs including AEs of special interest to any of the study interventions, clinical laboratory tests, ECGs, vital signs, and physical examinations.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 120
• Est. completion date: February 18, 2022
• Est. primary completion date: January 31, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

• Medically stable based on physical examination, medical history, vital signs, electrocardiogram (ECG) at screening

• Chronic hepatitis B virus (HBV) infection with documentation at least 6 months prior to screening

• Hepatitis B e (antigen) (HBeAg)-negative on stable nucleotide analogue (NA) treatment for at least 24 months prior to screening

• 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 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

• Liver fibrosis stage 0-2 (Metavir) or Fibroscan less than (<) 9 Kilopascal (kPa) at 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 or any laboratory abnormalities indicating a reduced liver function as defined in the protocol

• Evidence of liver disease of non-HBV etiology

• History or signs of cirrhosis or portal hypertension (nodules, no smooth liver contour, no normal portal vein, spleen size =12 cm) or signs of hepatocellular carcinoma (HCC)

• Significant laboratory abnormalities as defined in the protocol at screening

• Participants with a history of malignancy within 5 years before screening

• Abnormal sinus rhythm or ECG parameters at screening as defined in the protocol

• History of or current cardiac arrhythmia or history or clinical evidence of significant or unstable cardiac disease

• Participants with any current or previous illness for which, in the opinion of the investigator and/or sponsor, participation would not be in the best interest of the participant

• History of or current clinically significant skin disease or drug rash

• Known allergies, hypersensitivity, or intolerance to JNJ-73763989 and JNJ-56136379 or their excipients or to placebo content

• Contraindications to the use of entecavir (ETV), tenofovir disoproxil fumarate (TDF), or tenofovir alafenamide (TAF) per local prescribing information

• Participants who have taken any therapies disallowed per protocol

Related Conditions & MeSH terms

• Hepatitis
• Hepatitis A
• Hepatitis B
• Hepatitis B, Chronic
• Herpesviridae Infections
• Virus Diseases

Intervention

Drug:
• JNJ-73763989
JNJ-73763989 injection will be administered subcutaneously once every 4 weeks up to 48 weeks.
• JNJ-56136379
JNJ-56136379 tablets will be administered orally once daily up to 48 weeks.
• Placebo for JNJ-73763989
Matching placebo for JNJ-73763989 will be administered as subcutaneous injection up to 48 weeks.
• Placebo for JNJ-56136379
Matching placebo for JNJ-56136379 tablets will be administered orally up to 48 weeks.
• Entecavir (ETV) monohydrate
ETV tablet will be administered orally once daily up to 48 weeks as NA treatment.
• Tenofovir disoproxil fumarate (TDF)
TDF will be administered orally once daily up to 48 weeks as NA treatment.
• Tenofovir alafenamide (TAF)
TAF will be administered orally once daily up to 48 weeks as NA treatment.

Locations

Country	Name	City	State
Belgium	SGS Clinical Pharmacology Unit (located in ZNA Stuivenberg)	Antwerpen
Belgium	Cliniques Universitaires Saint-Luc	Bruxelles
Belgium	UZ Antwerpen	Edegem
Belgium	Universitair Ziekenhuis Gent	Gent
Belgium	UZ Leuven	Leuven
France	Hôpital Beaujon	Clichy
France	Hopital de La Croix Rousse	Lyon
France	Hopital Saint Joseph	Marseille
France	Hopital Cochin	Paris
France	Chu Rennes - Hopital Pontchaillou	Rennes
France	CHU Nancy Brabois	Vandoeuvre les Nancy
France	Hopital Paul Brousse	Villejuif
Germany	EPIMED GmbH	Berlin
Germany	Universitatsklinikum Essen	Essen
Germany	Universitätsklinikum Johann Wolfgang Goethe- Universität Frankfurt Medizinische Klinik 1	Frankfurt
Germany	Universitatsklinikum Freiburg	Freiburg
Germany	ICH Study Center GmbH & Co. KG	Hamburg
Germany	University Medical Center	Hamburg
Germany	Medizinische Hochschule Hannover	Hannover
Germany	Universitatsklinikum Leipzig	Leipzig
Germany	Universitätsmedizin der Johannes Gutenberg-Universität Mainz	Mainz
Italy	Azienda Ospedaliera Universitaria Policlinico G. Martino	Messina
Italy	Irccs Ospedale Maggiore Di Milano	Milano
Italy	Azienda Ospedaliero-Universitaria di Modena, Ospedale di Baggiovara	Modena
Italy	Azienda Ospedaliero Universitaria Pisana	Pisa
Italy	Universita degli Studi di Roma 'La Sapienza' - Umberto I Policlinico di Roma	Rome
Poland	Wojewodzki Szpital Obserwacyjno-Zakazny im. Tadeusza Browicza w Bydgoszczy	Bydgoszcz
Poland	Neutrum Lekarze M.Hlebowicz i Partnerzy spolka partnerska	Gdansk
Poland	ID Clinic	Myslowice
Poland	SP ZOZ Wroclawskie Centrum Zdrowia	Wroclaw
Spain	Hosp. Clinic I Provincial de Barcelona	Barcelona
Spain	Hosp. Univ. Vall D'Hebron	Barcelona
Spain	Hosp. Univ. 12 de Octubre	Madrid
Spain	Hosp. Univ. Pta. de Hierro Majadahonda	Madrid
Spain	Hosp. Univ. Marques de Valdecilla	Santander
Spain	Hosp. Gral. Univ. Valencia	Valencia
United Kingdom	Queen Elizabeth Hospital	Birmingham
United Kingdom	North Manchester General Hospital	Crumpsall
United Kingdom	Glasgow Royal Infirmary	Glasgow
United Kingdom	Grahame Hayton Unit	London
United Kingdom	Kings College Hospital	London
United Kingdom	St George's, University of London and St George's University Hospitals NHS Foundation Trust	London

Sponsors (1)

Lead Sponsor	Collaborator
Janssen Sciences Ireland UC

Countries where clinical trial is conducted

Belgium,  France,  Germany,  Italy,  Poland,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants with Hepatitis B Surface Antigen (HBsAg) Seroclearance at Week 72 (24 weeks after completion of all study interventions at Week 48) Without Restarting NA Treatment	Percentage of participants with HBsAg seroclearance at week 72 (24 weeks after completion of all study interventions at Week 48) without restarting nucleos(t)ide analog (NA) treatment will be reported.	Week 72
Secondary	Number of Participants with Adverse Events (AEs) and Serious AEs	An AE is any untoward medical occurrence in a clinical study participant administered a medicinal (investigational or non investigational) product. An AE does not necessarily have a causal relationship with the intervention. A SAE is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly.	Up to 102 weeks
Secondary	Number of Participants with Abnormalities in Clinical Laboratory Tests	Number of participants with abnormalities in clinically significant laboratory findings (urine chemistry and renal biomarkers) will be reported.	Up to 102 weeks
Secondary	Percentage of Participants with HBsAg Seroclearance at Week 48	Percentage of participants with HBsAg seroclearance at week 48 will be reported.	Week 48
Secondary	Percentage of Participants with HBV DNA less than (<) Lower Limit of Quantification (LLOQ) at Week 48	Percentage of participants with hepatitis B virus (HBV) deoxyribonucleic acid (DNA)	Week 48
Secondary	Percentage of Participants with HBsAg Seroclearance at Week 96 (48 Weeks After Completion of all Study Intervention) Without Restarting NA Treatment	Percentage of participants with HBsAg seroclearance up to week 96 (48 weeks after completion of all study intervention) without restarting NA treatment will be reported.	Up to Week 96
Secondary	Percentage of Participants with (Sustained) Reduction, Suppression, and/or Seroclearance	Percentage of participants with (sustained) reduction, suppression, and/or seroclearance considering single and multiple markers (such as hepatitis B surface antigen [HBsAg], hepatitis B e antigen [HBeAg], HBV DNA and alanine aminotransferase [ALT]) will be reported.	Up to Week 96
Secondary	Time to Achieve First HBsAg Seroclearance	Time to achieve first HBsAg seroclearance will be reported.	Up to Week 96
Secondary	Percentage of participants with HBV DNA levels with <LLOQ	Percentage of participants with HBV DNA levels with lower limit of quantification (	Up to Week 96
Secondary	Percentage of Participants with Virologic Breakthrough	Percentage of participants with virologic breakthrough defined as confirmed on-treatment HBV DNA increase by greater than (>)1 log10 IU/mL from nadir level or confirmed on treatment level >200 IU/mL in participants who had HBV DNA level below	Up to Week 48
Secondary	Percentage of Participants with Flares	Percentage of participants with flares (virologic, biochemical and clinical flares) will be reported.	Up to week 96
Secondary	Percentage of Participants Requiring NA Re-Treatment During Follow-up	Percentage of participants requiring NA re-treatment during follow-up will be reported.	Up to week 96
Secondary	Association Between Baseline Characteristics and On-Treatment Viral Blood Markers with Selected Off-Treatment Responses	Identification of baseline characteristics and on treatment viral blood markers (e.g., HBV DNA, HBsAg, ALT) associated with sustained off-treatment responses will be reported.	Baseline to week 72
Secondary	Area Under the Plasma Concentration-time Curve over the Dosing Interval (tau) at Steady-state (AUCtau,ss) of JNJ-73763989	The AUC (tau,ss) is the area under the plasma concentration time curve observed during a dosing interval (tau) at steady state.	Days 1, 29, 85, 169 and 337
Secondary	Area Under the Plasma Concentration-time Curve over the Dosing Interval (tau) at Steady-state (AUCtau,ss) of JNJ-56136379	The AUC (tau,ss) is the area under the plasma concentration time curve observed during a dosing interval (tau) at steady state.	Days 1, 29, 85, 169 and 337
Secondary	Area Under the Plasma Concentration-time Curve over the Dosing Interval (tau) at Steady-state (AUCtau,ss) of NA	The AUC (tau,ss) is the area under the plasma concentration time curve observed during a dosing interval (tau) at steady state.	Days 1, 29, 85, 169 and 337

External Links

•   To learn how to participate in this trial please click here.