A Study of JNJ-73763989, Pegylated Interferon Alpha-2a, Nucleos(t)Ide Analog (NA) With or Without JNJ-56136379 in Treatment-naive Participants With Hepatitis B e Antigen (HBeAg) Positive Chronic Hepatitis B Virus (HBV) Infection

Hepatitis B, Chronic Clinical Trial

Official title:

A Phase 2, Randomized, Open-label, Multicenter Study to Evaluate Efficacy, Pharmacokinetics, Safety, and Tolerability of Treatment With JNJ-73763989, Pegylated Interferon Alpha-2a, Nucleos(t)Ide Analog With or Without JNJ-56136379 in Treatment-naive Patients With HBeAg Positive Chronic Hepatitis B Virus Infection

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04439539
• Other study ID #: CR108815
• Secondary ID: 73763989PAHPB200
• Status: Completed
• Phase: Phase 2
• Start date: September 14, 2020
• Est. completion date: February 13, 2024

Study information

• Verified date: March 2024
• Source: Janssen Research & Development, LLC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to evaluate the efficacy of a treatment regimen of JNJ-73763989 + pegylated interferon alpha-2a (PegIFN-alpha-2a) + nucleos(t)ide analog (NA).

Description:

Hepatitis B virus (HBV) is a small deoxyribonucleic acid virus that specifically infects the human liver. The acute phase of infection is either followed by an immune controlled state or progresses to chronic hepatitis B. The worldwide estimated prevalence of chronic HBV infection is about 292 million people affected. Hepatitis B surface antigen (HBsAg) seroclearance is currently considered to be associated with the most thorough suppression of HBV replication (termed functional cure). With current available NA treatment strategies, rate of HBsAg seroclearance remains very low (around 3 percent [%]) even under long-term treatment. Also, with the persistently high global prevalence of HBV-associated mortality, there is a medical need for more effective finite treatment options that lead to sustained HBsAg seroclearance. JNJ-73763989 is a liver-targeted antiviral therapeutic for subcutaneous injection designed to treat chronic HBV infection via a ribonucleic acid interference (RNAi) mechanism. JNJ-56136379 is an orally administered capsid assembly modulator (CAM) that is being developed for the treatment of chronic HBV infection. The aim of the study is to evaluate the efficacy of a treatment regimen of JNJ-73763989 + PegIFN-alpha-2a + NA with or without JNJ-56136379 in participants with hepatitis B e antigen (HBeAg) positive chronic infection. The study will be conducted in 4 phases: a screening phase, an induction phase with flexible duration, a consolidation phase with or without PegIFN-α2a and a follow-up phase. Safety assessments will include Adverse Events (AEs), serious AEs of the study interventions, clinical laboratory tests, Electrocardiograms (ECGs), vital signs, and physical examinations. The study title reflects the original study design and JNJ-56136379 (JNJ-6379) was initially part of the study intervention but was discontinued as per amendment 6 of the study.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 54
• Est. completion date: February 13, 2024
• Est. primary completion date: August 29, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 55 Years

Eligibility

Inclusion Criteria:

• Medically stable based on physical examination, medical history, vital signs, laboratory values, and 12-lead Electrocardiogram (ECG) at screening

• Currently not treated chronic hepatitis B virus (HBV) infection with alanine transaminase (ALT) less than (<) 2* upper limit of normal (ULN) at screening and HBV deoxyribonucleic acid (DNA) greater than or equal to (>=) 20,000 international units per milliliter (IU/mL)

• Body mass index (BMI) between 18.0 and 35.0 kilogram per meter square (kg/m^2), extremes included

• Liver fibrosis stage 0-2 (Metavir) or Fibroscan less than or equal to (<=) 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 or symptoms of hepatic decompensation, including but not limited to: portal hypertension, ascites, hepatic encephalopathy, esophageal varices

• Evidence of liver disease of non-HBV etiology

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

• Participants who had or planned major surgery, (example, requiring general anesthesia) or who have received an organ transplant

• Contraindications to the use of PegIFN-a2a

Related Conditions & MeSH terms

• Hepatitis
• Hepatitis A
• Hepatitis B
• Hepatitis B, Chronic

Intervention

Drug:
• JNJ-73763989
JNJ-73763989 injection will be administered subcutaneously.
• PegIFN-alpha-2a
PegIFN-alpha-2a injection will be administered subcutaneously.
• Tenofovir disoproxil
Tenofovir disoproxil film-coated tablet will be administered orally.
• Tenofovir alafenamide
Tenofovir alafenamide film-coated tablet will be administered orally.
• JNJ-56136379
JNJ-56136379 will be administered orally.

Locations

Country	Name	City	State
Canada	University of Calgary	Calgary	Alberta
Canada	Toronto General Hospital	Toronto	Ontario
Canada	GI Research Institute (G.I.R.I.)	Vancouver	British Columbia
Canada	Vancouver ID Research and Care Centre Society	Vancouver	British Columbia
France	Hopital Beaujon	Clichy
France	CHU de Grenoble Hopital Albert Michallon	Grenoble
France	Hopital de La Croix Rousse	Lyon
France	CHU Nantes - Hotel Dieu	Nantes
France	CHU Hopital Saint Antoine	Paris
France	Chu Rennes Hopital Pontchaillou	Rennes
France	CHU Nancy Brabois	Vandoeuvre les Nancy
Germany	Zentrum für Infektiologie Berlin Prenzlauer Berg GmbH	Berlin
Germany	Universitatsklinikum Essen	Essen
Germany	Universitätsklinikum Johann Wolfgang Goethe- Universität Frankfurt Medizinische Klinik 1	Frankfurt
Germany	Medizinische Hochschule Hannover	Hannover
Japan	Hiroshima University Hospital	Hiroshima-shi
Japan	Nara Medical University Hospital	Kashihara
Japan	Musashino Red Cross Hospital	Musashino
Japan	Nagoya City University Hospital	Nagoya
Japan	Yokohama City University Medical Center	Yokohama
Russian Federation	Irkutsk State Medical University	Irkutsk
Russian Federation	Republic Clinical Infectious Hospital n.a. AF Agafonov	Kazan
Russian Federation	St. Petersburg City Center for AIDS and Infectious Diseases Treatment and Prophylaxis	Saint Petersburg
Russian Federation	Clinical Infectious Diseases Hospital n. a. S.P. Botkin	Saint-Petersburg
Russian Federation	Medical Company Hepatolog Ltd	Samara
Russian Federation	Smolensk Regional Clinical Hospital	Smolensk
Russian Federation	Stavropol State Medical University	Stavropol
Spain	Hosp. Clinic de Barcelona	Barcelona
Spain	Hosp. Univ. Vall D Hebron	Barcelona
Spain	Hosp. Gral. Univ. Valencia	Valencia
Taiwan	Kaohsiung Medical University Chung-Ho Memorial Hospital	Kaohsiung
Taiwan	China Medical University Hospital	Taichung
Taiwan	National Cheng Kung University Hospital	Tainan
Taiwan	National Taiwan University Hospital	Taipei
Turkey	Hacettepe University Hospital	Ankara
Turkey	Istanbul University Cerrahpasa Medical Faculty	Istanbul
Turkey	Umraniye Training and Research Hospital	Istanbul
Turkey	Ege University Medical of Faculty, Department of Gastroenterology	Izmir
Turkey	Acibadem Mehmet Ali Aydinlar University	Kucukcekmece
Turkey	Karadeniz Teknik University Medical Faculty	Trabzon
United Kingdom	Glasgow Royal Infirmary	Glasgow
United Kingdom	NHS Greater Glasgow and Clyde - Gartnavel General Hospital	Glasgow
United Kingdom	Grahame Hayton Unit	London
United Kingdom	Kings College Hospital	London
United States	Ruane Clinical Research Group Inc	Los Angeles	California
United States	UPMC Center For Liver Diseases	Pittsburgh	Pennsylvania
United States	Liver Institute Northwest	Seattle	Washington

Sponsors (1)

Lead Sponsor	Collaborator
Janssen Research & Development, LLC

Countries where clinical trial is conducted

United States,  Canada,  France,  Germany,  Japan,  Russian Federation,  Spain,  Taiwan,  Turkey,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants with Hepatitis B Surface Antigen (HBsAg) Seroclearance 24 Weeks After Stopping all Study Interventions of Consolidation Phase and Without Restarting NA Treatment	Percentage of participants with HBsAg seroclearance 24 weeks after stopping all study interventions of consolidation phase and without restarting nucleos(t)ide analog (NA) treatment will be reported.	Up to Follow-up Week 24
Secondary	Number of Participants with Adverse Events (AEs) and Serious AEs	An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study. 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 Week 102
Secondary	Number of Participants with Clinically Significant Abnormalities in Laboratory Parameters	Number of participants with clinically significant abnormalities in laboratory parameters (hematology, blood biochemistry, blood coagulation, urinalysis, urine chemistry, and renal biomarkers) will be reported.	Up to Week 102
Secondary	Number of Participants with Clinically Significant Abnormalities in Electrocardiogram (ECGs)	Number of participants with clinically significant abnormalities in electrocardiogram (ECGs) will be reported.	Up to Week 102
Secondary	Number of Participants with Clinically Significant Abnormalities in Vital Signs	Number of participants with clinically significant abnormalities in vital signs (systolic and diastolic blood pressure, pulse rate, and body temperature) will be reported.	Up to Week 102
Secondary	Number of Participants with Clinically Significant Abnormalities in Physical Examination	Number of participants with clinically significant abnormalities in physical examination will be reported.	Up to Week 102
Secondary	Percentage of Participants Reaching HBsAg less than (<) 10 IU/mL at the End of Induction Phase (Week 36)	Percentage of participants reaching HBsAg <10 international units per milliliter (IU/mL) at the end of induction phase (Week 36) will be reported.	Up to Week 48
Secondary	Time to Reach Hepatitis B Surface Antigen (HBsAG) < 10 IU/mL	Time to Reach HBsAG < 10 IU/mL will be reported.	Up to Week 102
Secondary	Percentage of Participants Meeting NA Treatment Completion Criteria at the end of Consolidation Phase	Percentage of participants meeting NA treatment completion criteria at the end of consolidation phase will be reported.	Up to Week 60
Secondary	Percentage of Participants with Hepatitis B Surface Antigen (HBsAg) Seroclearance	Percentage of participants with HBsAg Seroclearance will be reported.	Up to Week 102
Secondary	Percentage of Participants with HBV DNA less than (<) Lower Limit of Quantification (LLOQ)	Percentage of participants with hepatitis B virus (HBV) deoxyribonucleic acid (DNA)	Up to Week 102
Secondary	Number of Participants with Flares	Number of participants with flares (virologic, biochemical and clinical flares) will be reported.	Up to Week 102
Secondary	Percentage of Participants Requiring NA Re-treatment	Percentage of participants requiring NA re-treatment based on failure in NA treatment completion criteria will be reported.	Up to Week 102
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 102
Secondary	Percentage of Participants with Hepatitis B Surface Antigen (HBsAg) and Hepatitis B e Antigen (HBeAg) Seroconversion	Percentage of participants with HBsAg and HBeAg seroconversion will be reported.	Up to Week 102
Secondary	Time to Achieve Hepatitis B Surface Antigen (HBsAg) Seroclearance	Time to achieve HBsAg seroclearance will be reported.	Up to Week 102
Secondary	Time to Achieve Hepatitis B e Antigen (HBeAg) Seroclearance	Time to achieve hepatitis B e antigen (HBeAg) seroclearance will be reported.	Up to Week 102
Secondary	Time to Achieve Hepatitis B Virus (HBV) Deoxyribonucleic Acid (DNA) <LLOQ	Time to achieve HBV DNA	Up to Week 102
Secondary	Percentage of participants with Hepatitis B e Antigen (HBeAg), Hepatitis B Surface Antigen (HBsAg), and Hepatitis B Virus (HBV) Deoxyribonucleic Acid (DNA) Levels	Percentage of participants with HBeAg, HBsAg, and HBV DNA Levels will be reported.	Up to Week 102
Secondary	Change from Baseline in Hepatitis B e Antigen (HBeAg)	Change from baseline in HBeAg will be reported.	Baseline and Week 102
Secondary	Change from Baseline in Hepatitis B Surface Antigen (HBsAg)	Change from baseline in HBsAg will be reported.	Baseline and Week 102
Secondary	Change from Baseline in Hepatitis B Virus (HBV) Deoxyribonucleic Acid (DNA) Levels	Change from baseline in HBV DNA levels will be reported.	Baseline and Week 102
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 102
Secondary	Percentage of Participants who Reach Hepatitis B Virus (HBV) Deoxyribonucleic Acid (DNA) Undetectability After Re-start of NA Treatment During Follow-up	Percentage of participants who reach HBV DNA undetectability after re-start of NA treatment during follow-up will be reported.	Up to Week 102
Secondary	Maximum Observed Plasma Concentration (Cmax)	Cmax is the maximum observed plasma concentration.	Up to Day 253 postdose
Secondary	Area Under the Plasma Concentration-time Curve From Time Zero to 24 Hours [AUC (0- 24 hours)]	AUC (0- 24 hours) is the area under the plasma concentration-time curve from time zero to 24 hours.	Up to 24 hours postdose