Clinical trial NCT05005507: A Study of JNJ-73763989, Pegylated Interferon Alpha-2a and Nucleos(t)Ide Analogs in Participants With Chronic Hepatitis B Virus Infection
Official title: A Phase 2, Open-label, Multicenter Study to Assess Efficacy, Safety, Tolerability, and Pharmacokinetics of Treatment With JNJ-73763989, Nucleos(t)Ide Analogs, and Pegylated Interferon Alpha-2a in Patients With Chronic Hepatitis B Virus Infection
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Hepatitis B, Chronic
Lead sponsor: Janssen Research & Development, LLC
Sponsor class: INDUSTRY
First posted: 2021-08-13
Enrollment: 1
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to evaluate the efficacy in terms of hepatitis B surface antigen (HBsAg) changes from baseline for the treatment regimens of 24 weeks of JNJ-73763989 + 24 weeks of nucleos(t)ide analog (NA) + 12 or 24 weeks of pegylated interferon alpha-2a (PegIFN-alpha-2a) (with immediate or delayed start of PegIFN-alpha-2a treatment).

Detailed description: JNJ-73763989 (JNJ-3989) 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. Combination treatment with JNJ-73763989 and NA has the potential to specifically decrease HBV viral antigen levels and inhibit viral replication. Since HBsAg is immune suppressive, the direct reduction of HBsAg levels by JNJ-73763989 is anticipated to contribute to the restoration of the immune response that is impaired in chronic HBV infection. Pegylated interferon (PegIFN) is an approved drug for the treatment of chronic HBV infection and after a finite treatment duration of 48 weeks results in slightly increased HBsAg seroclearance rates. The primary hypothesis of this study is that at least one of the combination regimens of JNJ-73763989+NA+PegIFN-alpha-2a is more efficacious than NA treatment alone (standard of care), as measured by the primary efficacy endpoint. This study will be conducted in 3 periods: Screening Period (4 weeks), Treatment Period (24 weeks) and Follow-up (FU) Period (48 weeks), starting at Week 24. Safety assessments will include adverse events (AEs), serious AEs, clinical safety laboratory tests, electrocardiograms (ECGs), vital signs, ophthalmologic examinations and physical examinations. Total duration of individual participation will be up to 76 weeks (including screening period).

Eligibility criteria: Inclusion Criteria:

* Medically stable based on physical examination, medical history, vital signs, and 12-lead electrocardiogram (ECG) performed at screening
* Participants must have a body mass index between 18.0 and 35.0 kilograms per meter square (kg/m\^2) inclusive
* Participants with chronic hepatitis B who should: a) be chronic hepatitis B e antigen (HBeAg) -negative; b) be anti-HBe antibody-positive; c) be currently receiving nucleos(t)ide analog (NA) treatment for at least 2 years prior to screening; d) have serum hepatitis B virus (HBV) deoxyribonucleic acid (DNA) less than (\<) 60 international unit/milliliter (IU/mL) on 2 sequential measurements at least 6 months apart; e) have alanine aminotransferase (ALT) values \< 2.0x upper limit of normal (ULN) on 2 sequential measurements at least 6 months apart
* Hepatitis B surface antigen (HBsAg) greater than (\>) 5 IU/mL at screening
* Fibroscan liver stiffness measurement less than or equal to (\<=) 9.0 kilopascal (kPa) within 6 months prior to screening

Exclusion Criteria:

* History or signs of cirrhosis or portal hypertension
* Evidence of hepatitis A, C, D, E virus infection, or human immunodeficiency virus (HIV) infection
* Liver disease of non-HBV etiology
* Clinically relevant alcohol or drug abuse within 12 months of screening
* Participants who meet any of the additional exclusion criteria for pegylated interferon alpha-2a (PegIFN- α2a) as described in local prescribing information (example, refer to Pegasys SmPC or Pegasys USPI) per the investigator's discretion. Key exclusion criteria for PegIFN- α2a include: a) Participants with signs or symptoms compatible with autoimmune disorders. b) Participants with bone marrow suppression. c) Participants with hypoglycaemia, hyperglycaemia, and/or diabetes mellitus, who cannot be effectively controlled by medication. d) Participants with pre-existing ophthalmologic disorders. e) Participants with one or more of the following laboratory abnormalities: i) Absolute neutrophil count less than (\<)1,500 cells/mm3 (\<1,000 cells/mm³ for black or African American participants). ii) Serum creatinine \>1.5x ULN. iii) Inadequately controlled thyroid function (thyroid stimulating hormone \[TSH\] and thyroxine \[T4\]). f) Participants with a history of a severe psychiatric disorder including severe depression, suicidal ideation and attempted suicide, or a current depression or other psychiatric disorder that is not adequately controlled on a stable medication regimen

Primary outcomes:
measure: Percentage of Participants With a Reduction of at Least 2log10 International Units Per Milliliter (IU/mL) in Hepatitis B Surface Antigen (HBsAg) Levels From Baseline at Week 24 (End of Study Intervention [EOSI])
timeFrame: Week 24
Secondary outcomes:
measure: Percentage of Participants With Adverse Events (AEs)
timeFrame: Up to 1 month 26 days
measure: Percentage of Participants With Serious Adverse Events (SAEs)
timeFrame: Up to 1 month 26 days
measure: Percentage of Participants With Abnormalities in Clinical Laboratory Tests
timeFrame: Up to 1 month 26 days
measure: Percentage of Participants With Abnormalities in 12-Lead Electrocardiograms (ECGs)
timeFrame: Up to 1 month 26 days
measure: Percentage of Participants With Abnormalities in Vital Signs
timeFrame: Up to 1 month 26 days
measure: Percentage of Participants With Abnormalities in Ophthalmologic Examination
timeFrame: Weeks 8 and 20
measure: Percentage of Participants With Abnormalities in Physical Examination
timeFrame: Week 24
measure: Percentage of Participants Meeting the Protocol-defined Nucleos(t)Ide Analog (NA) Treatment Completion Criteria Based on the Week 24 (EOSI) or Follow-up Week 2 Visits
timeFrame: Week 24 (EOSI) and follow-up Week 2
measure: Percentage of Participants With HBsAg Seroclearance at Follow-up Weeks 24 and 48 Without Re-starting NA Treatment
timeFrame: Follow-up Weeks 24 and 48
measure: Percentage of Participants With Hepatitis B Virus (HBV) Deoxyribonucleic Acid (DNA) < (Less Than) LLOQ at Follow-up Weeks 24 and 48 Without Re-starting NA Treatment
timeFrame: Follow-up Weeks 24 and 48
measure: Percentage of Participants With Virologic Flares
timeFrame: Up to 1 month 26 days
measure: Percentage of Participants With Biochemical Flares
timeFrame: Up to 1 month 26 days
measure: Percentage of Participants Requiring Nucleos(t)Ide Analog (NA) Re-treatment
timeFrame: Up to 72 weeks
measure: Percentage of Participants With HBsAg, Hepatitis B e Antigen (HBeAg), HBV DNA, and Alanine Aminotransferase (ALT) Levels Below/Above Different Cut-offs
timeFrame: Up to 72 weeks
measure: Percentage of Participants With HBsAg Seroconversion
timeFrame: Up to 72 weeks
measure: Change From Baseline in HBsAg Over Time
timeFrame: Baseline up to Week 72
measure: Time to Achieve HBsAg Seroclearance
timeFrame: Up to 72 weeks
measure: Time to Achieve HBsAg Seroconversion
timeFrame: Up to 72 weeks
measure: Time to Achieve HBV DNA <Lower Limit of Quantitation (LLOQ)
timeFrame: Up to 72 weeks
measure: Percentage of Participants With Virologic Breakthrough
timeFrame: Up to Week 24
measure: Serum Concentration of JNJ-73763989 (JNJ-73763924 and JNJ-73763976)
timeFrame: Up to 72 weeks
measure: Serum Concentration of Nucleos(t)Ide Analog (NA) (Entecavir [ETV])
timeFrame: Up to 72 weeks
measure: Serum Concentration of PegIFN-alpha-2a
timeFrame: Up to 72 weeks
Other outcomes:
Locations:
city: Hillsborough
country: United States
facility: I.D. Care, Inc.
state: New Jersey
city: Vancouver
country: Canada
facility: Vancouver ID Research and Care Centre Society
state: British Columbia
city: Vancouver
country: Canada
facility: GI Research Institute (G.I.R.I.)
state: British Columbia
city: Takamatsu
country: Japan
facility: Kagawa Prefectural Central Hospital
city: Gdansk
country: Poland
facility: PUNKT ZDROWIA Hlebowicz Jakubowski Lekarze sp.p.
city: Mysłowice
country: Poland
facility: ID Clinic
city: Wroclaw
country: Poland
facility: EMC Instytut Medyczny SA
city: Barcelona
country: Spain
facility: Hosp. Univ. Vall D Hebron
city: Madrid
country: Spain
facility: Hosp. Univ. Infanta Leonor
city: Santander
country: Spain
facility: Hosp. Univ. Marques de Valdecilla
city: Vigo
country: Spain
facility: Hosp. Alvaro Cunqueiro
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: