A Study of JNJ-73763989, JNJ-64300535, and Nucleos(t)Ide Analogs in Virologically Suppressed, Hepatitis B e Antigen (HBeAg)- Negative Participants With Chronic Hepatitis B Virus Infection

Hepatitis B, Chronic Clinical Trial

— OSPREY  

Official title:

A Phase 1b, Open-label, Single-arm, Multicenter Study to Assess Efficacy, Safety, and Tolerability of Treatment With JNJ-73763989, JNJ-64300535, and Nucleos(t)Ide Analogs in Virologically Suppressed, HBeAg-negative Participants With Chronic Hepatitis B Virus Infection

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05123599
• Other study ID #: CR109042
• Secondary ID: 2020-005584-3073
• Status: Active, not recruiting
• Phase: Phase 1
• Start date: December 6, 2021
• Est. completion date: August 2, 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 the study intervention based on hepatitis B surface antigen (HBsAg) levels.

Description:

JNJ-73763989 is a liver-targeted antiviral therapeutic for subcutaneous injection designed to treat chronic hepatitis B virus (HBV) infection via a ribonucleic acid interference (RNAi) mechanism. JNJ-64300535 is a DNA vaccine encoding the core protein and the Polymerase (Pol) protein of HBV. The therapeutic vaccine aims at inducing T-cell-specific immunity against HBV antigens in participants with chronic hepatitis B (CHB). Selected nucleos(t)ide analogs (NAs) used in this study are approved treatments of chronic HBV infection. This study is designed to assess efficacy, safety, and tolerability of a 24-week (Day 1 to Week 24) combination treatment with JNJ-73763989 + NA + JNJ-64300535. The study consists of a Screening phase (4 weeks), Treatment period with JNJ-73763989, NA and JNJ-64300535 (187 days), and a follow-up period (FU Week 1 till FO Week 48). Safety will be assessed by adverse events (AEs), clinical safety laboratory assessments, electrocardiograms (ECGs), vital signs and physical examinations. The total duration of the study is up to 88 weeks (including 4 weeks of screening).

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 24
• Est. completion date: August 2, 2024
• Est. primary completion date: July 31, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 60 Years

Eligibility

Inclusion Criteria:

• Participants must be medically stable based on physical examination, medical history, vital signs, and 12-lead electrocardiogram (ECG) performed at screening. Any abnormalities, must be consistent with the underlying illness in the study population and this determination must be recorded in the participant's source documents and initialed by the investigator
• Participants must have a body mass index (BMI; weight in kilograms [kg] divided by the square of height in meters) between 19.0 and 32.0 kilograms per meter square (kg/m^2), extremes included
• A woman of childbearing potential must have a negative highly sensitive serum pregnancy test (beta-human chorionic gonadotropin) at screening and a negative urine pregnancy test on Day 1 before the first dose of study intervention
• Participants must have chronic hepatitis B virus (HBV) infection. HBV infection must be documented by serum hepatitis B surface antigen (HBsAg) positivity at screening. In addition, chronicity must be documented by any of the following, at least 6 months prior to screening: serum HBsAg positivity, hepatitis B e antigen (HBeAg) positivity or HBV deoxyribonucleic acid (DNA) positivity, alanine aminotransferase (ALT) elevation above upper limit of normal (ULN) without another cause than HBV infection, documented transmission event. If none of the above are available, the following ways of documenting chronicity are acceptable at the time of screening: liver biopsy with changes consistent with chronic HBV, or absence of marker for acute HBV infection such as positive immunoglobulin M (IgM) anti- hepatitis B surface protein (HBs) and anti- hepatitis B core protein (HBc) antibodies. Virologically suppressed participants should: a) be HBeAg-negative and anti- hepatitis B e (HBe) positive, b) be on stable HBV treatment, defined as currently receiving nucleos(t)ide analog (NA) treatment for at least 6 months prior to screening and having been on the same NA treatment regimen (at the same dose) as used in this study for at least 3 months at the time of screening, c) have serum HBV deoxyribonucleic acid (DNA) less than (<) 60 International units per milliliter (IU/mL) on 2 sequential measurements at least 6 months apart (one of which is at screening), and d) have documented ALT values <2.0* ULN on 2 sequential measurements at least 6 months apart (one of which is at screening)
• Participants must have: a) Fibroscan liver stiffness measurement less than or equal to (<=) 9.0 kPa within 6 months prior to screening or at the time of screening, or b) If a Fibroscan result is not available: a liver biopsy result classified as Metavir F0-F2 within 1 year prior to screening

Exclusion Criteria:

• History or evidence of clinical signs or symptoms of hepatic decompensation, including but not limited to: portal hypertension, ascites, hepatic encephalopathy, esophageal varices
• Participants with a history of malignancy within 5 years before screening (exceptions are squamous and basal cell carcinomas of the skin and carcinoma in situ of the cervix, or malignancy, which are considered cured with minimal risk of recurrence)
• Participants with any history of or current clinically significant skin disease requiring regular or periodic treatment
• Participants with clinically relevant alcohol or drug abuse within 12 months of screening
• Participants who had major surgery (example, requiring general anesthesia), excluding diagnostic surgery, within 12 weeks before screening; or will not have fully recovered from surgery; or have surgery planned during the time of expected participation in the study

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.

Biological:
• JNJ-64300535
JNJ-64300535 deoxyribonucleic acid (DNA) vaccine injection will be administered intramuscularly.

Drug:
• ETV monohydrate
ETV monohydrate film-coated tablets will be administered orally.
• Tenofovir disoproxil
Tenofovir disoproxil film-coated tablets will be administered orally.
• TAF
TAF film-coated tablets will be administered orally.

Locations

Country	Name	City	State
Belgium	UZ Antwerpen	Edegem
Belgium	UZA-SGS	Edegem
France	Hopital Beaujon	Clichy
France	Hopital de La Croix Rousse	Lyon
Italy	Irccs Ospedale Maggiore Di Milano	Milano
Italy	Azienda Ospedaliero Universitaria Pisana	Pisa
New Zealand	New Zealand Clinical Research	Auckland
Poland	ID Clinic	Myslowice
Spain	Hosp. Univ. Vall D Hebron	Barcelona
Spain	Hosp. Univ. Marques de Valdecilla	Santander
Taiwan	E-DA Hospital	Kaohsiung City
Taiwan	Chang Gung Memorial Hospital Linkou Branch	Tao-Yuan
United Kingdom	Kings College Hospital	London

Sponsors (1)

Lead Sponsor	Collaborator
Janssen Research & Development, LLC

Countries where clinical trial is conducted

Belgium,  France,  Italy,  New Zealand,  Poland,  Spain,  Taiwan,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants with a Reduction of at Least 2 log10 International Units per Milliliter (IU/mL) in Hepatitis B Surface Antigen (HBsAg) Levels from Baseline to Week 36	Percentage of participants with a reduction of at least 2 log10 IU/mL in HBsAg levels from baseline to Week 36 will be reported.	Baseline to Week 36 (end of study intervention)
Secondary	Percentage of Participants with at Least 3-fold Increase in Hepatitis B Virus (HBV)- Specific T-Cell Response Against Vaccine Antigen HBV Core and/or Pol	Percentage of participants with at least 3-fold increase in HBV-specific T-cell response against vaccine antigen HBV core and/or pol as assessed by enzyme-linked immunospot (ELISpot) will be reported.	From Day 103 up to Week 84
Secondary	Percentage of Responders Against Vaccine Antigen HBV Core and/or Pol	Percentage of responders against vaccine antigen HBV core and/or Pol as assessed by ELISpot will be reported. A responder is defined as a participant with at least a 3-fold increase in HBV-specific T-cell response from the start of vaccination against the vaccine antigen core and/or pol, at least at the last timepoint during the vaccination period.	Week 28
Secondary	Percentage of Participants with Adverse Events (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.	Up to Week 84
Secondary	Percentage of Participants with Serious AEs	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 84
Secondary	Percentage of Participants with Abnormalities in Clinical Laboratory Tests	Percentage of participants with abnormalities in clinical laboratory tests (hematology, blood biochemistry, blood coagulation, urinalysis, urine chemistry, and renal biomarkers) will be reported.	Up to Week 84
Secondary	Percentage of Participants with Abnormalities in 12- lead Electrocardiograms (ECGs)	Percentage of participants with abnormalities in 12- lead ECGs will be reported.	Up to Week 84
Secondary	Percentage of Participants with Abnormalities in Vital Signs	Percentage of participants with abnormalities in vital signs will be reported.	Up to Week 84
Secondary	Percentage of Participants with Abnormalities in Physical Examinations	Percentage of participants with abnormalities in physical examinations will be reported.	Up to Week 84
Secondary	Percentage of Participants with Solicited Local AEs for JNJ-64300535 up to 7 Days Post Each Vaccination	Solicited local AEs include (injection site pain/tenderness, erythema and swelling at the study vaccine injection site and the extent (largest diameter) of any erythema and swelling [using the ruler supplied]) will be reported after 7 days of each vaccination.	7 days post each vaccination (Up to Day 194)
Secondary	Percentage of Participants with Solicited Systematic AEs for JNJ-64300535 up to 7 Days Post Each Vaccination	Solicited systemic AEs (include body temperature, fatigue, headache, nausea, myalgia) will be reported after 7 days of each vaccination.	7 days post each vaccination (Up to Day 194)
Secondary	Change from Baseline Over Time in HBsAg Levels	Change from baseline over time in HBsAg levels will be reported.	Baseline up to Week 84
Secondary	Change from Start of Vaccination Over Time in HBsAg Levels	Change from start of vaccination over time in HBsAg levels will be reported.	From Day 103 up to Week 84
Secondary	Percentage of Participants with HBsAg, HBV Deoxyribonucleic Acid (DNA) and Alanine Aminotransferase (ALT) Levels Below/Above Different Cut-offs	Percentage of participants with HBsAg, HBV DNA and ALT levels below/above different cut-offs will be reported.	Up to Week 84
Secondary	Percentage of Participants with HBsAg Seroclearance	Percentage of participants with HBsAg seroclearance (HBsAg negativity) will be reported.	Up to Week 84
Secondary	Percentage of Participants with HBsAg Seroconversion	Percentage of participants with HBsAg seroconversion (HBsAg negativity and anti-HBs antibody positivity) will be reported.	Up to Week 84
Secondary	Time to Achieve HBsAg Seroclearance	Time to achieve HBsAg seroclearance will be reported.	Up to Week 84
Secondary	Time to Achieve HBsAg Seroconversion	Time to achieve HBsAg seroconversion will be reported.	Up to Week 84
Secondary	Percentage of Participants Meeting Nucleos(t)ide Analog (NA) Treatment Completion Criteria	Percentage of participants meeting NA treatment completion criteria will be reported.	Week 38 and Week 40
Secondary	Percentage of Participants with Virological Breakthrough	Percentage of participants with virological breakthrough (confirmed on-treatment HBV DNA increase by greater than [>] 1 log10 IU/mL from nadir or confirmed on-treatment HBV DNA level >200 IU/mL in participants who had HBV DNA level less than [<] lower limit of quantification [LLOQ] of the HBV DNA assay) will be reported.	Up to Week 36
Secondary	Percentage of Participants with HBsAg Seroclearance at Week 60 and Week 84	Percentage of participants with HBsAg seroclearance at Weeks 60 and 84 (during follow-up period) will be reported.	Weeks 60 and 84
Secondary	Percentage of Participants with HBV DNA <LLOQ at Week 60 and Week 84	Percentage of participants with HBV DNA	Weeks 60 and 84
Secondary	Percentage of Participants with Viral Flares	Percentage of participants with viral flares will be reported.	From Week 36 to Week 84
Secondary	Percentage of Participants with Biochemical Flares	Percentage of participants with biochemical flares will be reported.	From Week 36 to Week 84
Secondary	Number of TriGrid Delivery System (TDS)-Intramuscular (IM) version 2.0 Device Fault Conditions by Type	Number of TDS-IM v2.0 device fault conditions by type will be observed. User reported fault conditions will be documented to enable assessment of the device reliability. Device functions to be assessed include electrode/needle deployment, JNJ-64300535 administration, and electroporation application.	From Day 103 to Day 187