Clinical trial NCT04667104: A Study of JNJ-73763989, JNJ-56136379, Nucleos(t)Ide Analogs, and Pegylated Interferon Alpha-2a in Virologically Suppressed Participants With Chronic Hepatitis B Virus Infection
Official title: A Phase 2, Open-label, Single-arm, Multicenter Study to Assess Efficacy, Safety, Tolerability, and Pharmacokinetics of Treatment With JNJ-73763989, JNJ-56136379, Nucleos(t)Ide Analogs, and Pegylated Interferon Alpha-2a in Virologically Suppressed Patients With Chronic Hepatitis B Virus Infection
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Hepatitis B, Chronic
Lead sponsor: Janssen Research & Development, LLC
Sponsor class: INDUSTRY
First posted: 2020-12-14
Enrollment: 48
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to evaluate the efficacy in terms of hepatitis B surface antigen (HBsAg) levels of the study intervention (that is, JNJ-73763989 + JNJ-56136379 + nucleos\[t\]ide analog \[NA\] and pegylated interferon alpha-2a \[PegIFN-alpha2a\]).

Detailed description: This study is an intervention specific appendix to the Hepatitis B wings platform trial (PLATFORMPAHPB2001). The study title reflects the original study design and JNJ-56136379 (JNJ-6379) was initially part of the study intervention but has been removed as part of amendment 3 of the study.

Eligibility criteria: Inclusion Criteria:

* Chronic hepatitis B virus (HBV) infection, hepatitis B e Antigen (HBeAg) positive or negative with suppressed viral replication under nucleos(t)ide analogue treatment for at least 6 months prior to screening
* Medically stable based on physical examination, medical history, vital signs, and 12-lead electrocardiogram (ECG) performed at screening
* Body mass index (BMI) between 18.0 and 35.0 kilogram per meter square (kg/m\^2), extremes included
* Must have serum HBsAg greater than (\>) 100 international units per milliliter (IU/mL) at screening, as assessed by quantitative HBsAg assay
* Must have a fibroscan stiffness measurement less than or equal to (\<=) 9.0 Kilopascal (kPa) at screening

Exclusion Criteria:

* Evidence of hepatitis A, C, D or E virus infection or human immunodeficiency, virus type 1 (HIV) 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
* Contraindications to the use of pegylated interferon alpha-2a

Primary outcomes:
measure: Percentage of Participants With a Reduction of at Least 2 log10 International Unit/Millilitres (IU/mL) in Hepatitis B Surface Antigen (HBsAg) Levels From Baseline to Week 24
timeFrame: From Baseline (Day 1) to Week 24
Secondary outcomes:
measure: Percentage of Participants With Treatment Emergent Adverse Events (TEAEs) as a Measure of Safety and Tolerability
timeFrame: Treatment Period 1: From Baseline (Day 1) up to Week 12; Treatment Period 2: From Week 12 up to Week 24; Follow-Up Period: From Week 24 up to follow-up Week 48 (with window period of +/- 4 days, that is Week 72.4)
measure: Percentage of Participants With Serious Adverse Events (SAEs) as a Measure of Safety and Tolerability
timeFrame: Treatment Period 1: From Baseline (Day 1) up to Week 12; Treatment Period 2: From Week 12 up to Week 24; Follow-Up Period: From Week 24 up to follow-up Week 48 (with window period of +/- 4 days, that is Week 72.4)
measure: Number of Participants With Clinically Significant Abnormalities in Vital Signs as a Measure of Safety and Tolerability
timeFrame: Treatment Period 1: From Baseline (Day 1) up to Week 12; Treatment Period 2: From Week 12 up to Week 24; Follow-Up Period: From Week 24 up to follow-up Week 48 (with window period of +/- 4 days, that is Week 72.4)
measure: Number of Participants With Clinically Significant Abnormalities in Laboratory Findings as a Measure of Safety and Tolerability
timeFrame: Treatment Period 1: From Baseline (Day 1) up to Week 12; Treatment Period 2: From Week 12 up to Week 24; Follow-Up Period: From Week 24 up to follow-up Week 48 (with window period of +/- 4 days, that is Week 72.4)
measure: Number of Participants With Clinically Significant Abnormalities in 12-Lead Electrocardiogram (ECGs) as a Measure of Safety and Tolerability
timeFrame: Treatment Period 1: From Baseline (Day 1) up to Week 12; Treatment Period 2: From Week 12 up to Week 24; Follow-Up Period: From Week 24 up to Week 28
measure: Number of Participants With Clinically Significant Abnormalities in Physical Examination as a Measure of Safety and Tolerability
timeFrame: Treatment Period 1: From Baseline (Day 1) up to Week 12; Treatment Period 2: From Week 12 up to Week 24
measure: Number of Participants With Abnormalities in Ophthalmic Examination as a Measure of Safety and Tolerability
timeFrame: Treatment Period 1: From Baseline (Day 1) up to Week 12; Treatment Period 2: From Week 12 up to Week 24
measure: Percentage of Participants Meeting the Protocol-defined Nucleos(t)Ide Analog (NA) Treatment Completion Criteria at End of Study Intervention (EOSI)
timeFrame: At Week 24 (EOSI)
measure: Percentage of Participants With Hepatitis B e Antigen (HBeAg) Levels Below Different Cut-offs
timeFrame: Treatment Period 1: From Baseline (Day 1) up to Week 12; Treatment Period 2: From Week 12 up to Week 24; Follow-Up Period: From Week 24 up to follow-up Week 48 (with window period of +/- 4 days, that is Week 72.4)
measure: Percentage of Participants With HBsAg Levels Below Different Cut-offs
timeFrame: Treatment Period 1: From Baseline (Day 1) up to Week 12; Treatment Period 2: From Week 12 up to Week 24; Follow-Up Period: From Week 24 up to follow-up Week 48 (with window period of +/- 4 days, that is Week 72.4)
measure: Percentage of Participants With Hepatitis B Virus (HBV) Deoxyribonucleic Acid (DNA) Levels Below Different Cut-offs
timeFrame: Treatment Period 1: From Baseline (Day 1) up to Week 12; Treatment Period 2: From Week 12 up to Week 24; Follow-Up Period: From Week 24 up to follow-up Week 48 (with window period of +/- 4 days, that is Week 72.4)
measure: Percentage of Participants With ALT Levels Greater Than or Equal to (>=) 3*ULN
timeFrame: Treatment Period 1: From Baseline (Day 1) up to Week 12; Treatment Period 2: From Week 12 up to Week 24; Follow-Up Period: From Week 24 up to follow-up Week 48 (with window period of +/- 4 days, that is Week 72.4)
measure: Percentage of Participants With HBeAg Seroconversion
timeFrame: Treatment Period 1: From Baseline (Day 1) up to Week 12; Treatment Period 2: From Week 12 up to Week 24; Follow-Up Period: From Week 24 up to follow-up Week 48 (with window period of +/- 4 days, that is Week 72.4)
measure: Percentage of Participants With HBsAg Seroconversion
timeFrame: Treatment Period 1: From Baseline (Day 1) up to Week 12; Treatment Period 2: From Week 12 up to Week 24; Follow-Up Period: From Week 24 up to follow-up Week 48 (with window period of +/- 4 days, that is Week 72.4)
measure: Change From Baseline Over Time in HBsAg Levels
timeFrame: Treatment Period 1: From Baseline (Day 1) up to Week 12; Treatment Period 2: From Baseline (Day 1) up to Week 24; Follow-Up: From Baseline (Day 1) up to follow-up Week 48 (with window period of +/- 4 days, that is Week 72.4)
measure: Change From Baseline Over Time in HBeAg Levels
timeFrame: Treatment Period 1: From Baseline (Day 1) up to Week 12; Treatment Period 2: From Baseline (Day 1) up to Week 24; Follow-Up: From Baseline (Day 1) up to follow-up Week 48 (with window period of +/- 4 days, that is Week 72.4)
measure: Change From Baseline Over Time in HBV DNA Levels
timeFrame: Treatment Period 1: From Baseline (Day 1) up to Week 12; Treatment Period 2: From Baseline (Day 1) up to Week 24; Follow-Up: From Baseline (Day 1) up to follow-up Week 48 (with window period of +/- 4 days, that is Week 72.4)
measure: Time to First Occurrence of HBsAg Seroclearance
timeFrame: From Baseline (Day 1) up to follow-up Week 48 (with window period of +/- 4 days, that is Week 72.4)
measure: Time to First Occurrence of HBeAg Seroclearance
timeFrame: From Baseline (Day 1) up to follow-up Week 48 (with window period of +/- 4 days, that is Week 72.4)
measure: Time to First Occurrence of HBV DNA < LLOQ
timeFrame: From Baseline (Day 1) up to follow-up Week 48 (with window period of +/- 4 days, that is Week 72.4)
measure: Percentage of Participants With Virologic Breakthrough
timeFrame: Treatment Period 1: From Baseline (Day 1) up to Week 12; Treatment Period 2: From Week 12 up to Week 24; Follow-Up: From Week 24 up to follow-up Week 48 (with window period of +/- 4 days, that is Week 72.4)
measure: Percentage of Participants With HBsAg Seroclearance at Week 48 Without Re-starting NA Treatment
timeFrame: At Week 48 (24 weeks after completion of all study interventions at Week 24)
measure: Percentage of Participants With HBV DNA < LLOQ at Week 48 Without Re-starting NA Treatment
timeFrame: At Week 48 (24 weeks after completion of all study interventions at Week 24)
measure: Percentage of Participants With Biochemical Flares
timeFrame: Treatment Period 1: From Baseline (Day 1) up to Week 12; Treatment Period 2: From Week 12 up to Week 24; Follow-Up: From Week 24 up to follow-up Week 48 (with window period of +/- 4 days, that is Week 72.4)
measure: Percentage of Participants With Virologic Flares
timeFrame: Follow-Up Period: From Week 24 up to follow-up Week 48 (with window period of +/- 4 days, that is Week 72.4)
measure: Number of Participants Requiring NA Re-treatment
timeFrame: Follow-Up Period: From Week 24 up to follow-up Week 48 (with window period of +/- 4 days, that is Week 72.4)
measure: Maximum Observed Plasma Concentration (Cmax) of JNJ-73763989 (JNJ-73763976 and JNJ-73763924)
timeFrame: Treatment Period 1: Day 1 Week 1; Treatment Period 2: Day 1, Week 12
measure: Plasma Concentration 24 Hours After Administration (C24h) of JNJ-73763989 (JNJ-73763976 and JNJ-73763924)
timeFrame: Treatment Period 1: Day 1 Week 1; Treatment Period 2: Day 1, Week 12
measure: Time to Reach Maximum Observed Plasma Concentration (Tmax) of JNJ-73763989 (JNJ-73763976 and JNJ-73763924)
timeFrame: Treatment Period 1: Day 1, Week 1; Treatment Period 2: Day 1, Week 12
measure: Area Under the Plasma Concentration Versus Time Curve From Time 0 to 24 Hour (AUC[0-24]h) of JNJ-73763989 (JNJ-73763976 and JNJ-73763924)
timeFrame: Treatment Period 1: Day 1, Week 1; Treatment Period 2: Day 1, Week 12
Other outcomes:
Locations:
city: Bunkyo Ku
country: Japan
facility: Tokyo Medical and Dental University Hospital
city: Suita-shi
country: Japan
facility: Osaka University Hospital
city: Auckland
country: New Zealand
facility: New Zealand Clinical Research
city: Papatoetoe
country: New Zealand
facility: Middlemore Clinical Trials
city: Gdansk
country: Poland
facility: Neutrum Lekarze M.Hlebowicz i Partnerzy spolka partnerska
city: Myslowice
country: Poland
facility: ID Clinic
city: Warszawa
country: Poland
facility: Wojewodzki Szpital Zakazny w Warszawie
city: Wroclaw
country: Poland
facility: Przychodnia EuroMediCare Wroclaw Lowiecka
city: Kaohsiung
country: Taiwan
facility: Kaohsiung Medical University Hospital
city: Taichung
country: Taiwan
facility: China Medical University Hospital
city: Tainan
country: Taiwan
facility: National Cheng Kung University Hospital
Study officials:
affiliation: Janssen Research & Development, LLC
name: Janssen Research & Development, LLC Clinical Trial
role: STUDY_DIRECTOR
References: