A Study of JNJ-73763989, Pegylated Interferon Alpha-2a and Nucleos(t)Ide Analogs in Participants With Chronic Hepatitis B Virus Infection

Hepatitis B, Chronic Clinical Trial

— PENGUIN-2  

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT05005507
• Other study ID #: CR109070
• Secondary ID: 2021-002450-8173
• Status: Terminated
• Phase: Phase 2
• Start date: November 3, 2021
• Est. completion date: December 29, 2021

Study information

• Verified date: January 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 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).

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).

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 1
• Est. completion date: December 29, 2021
• Est. primary completion date: December 29, 2021
• 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, 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- a2a) as described in local prescribing information (example, refer to Pegasys SmPC or Pegasys USPI) per the investigator's discretion. Key exclusion criteria for PegIFN- a2a 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

Related Conditions & MeSH terms

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

Intervention

Drug:
• JNJ-73763989
JNJ-73763989 will be administered subcutaneously once every 4 weeks.
• PegIFN-alpha-2a
PegIFN-alpha-2a will be administered subcutaneously once weekly.
• Tenofovir disoproxil
Tenofovir disoproxil film-coated tablet will be administered orally once daily.
• TAF
TAF film-coated tablet will be administered orally once daily.
• ETV
ETV film-coated tablet will be administered orally once daily.

Locations

Country	Name	City	State
Canada	GI Research Institute (G.I.R.I.)	Vancouver	British Columbia
Canada	Vancouver ID Research and Care Centre Society	Vancouver	British Columbia
Japan	Kagawa Prefectural Central Hospital	Takamatsu
Poland	PUNKT ZDROWIA Hlebowicz Jakubowski Lekarze sp.p.	Gdansk
Poland	ID Clinic	Myslowice
Poland	EMC Instytut Medyczny SA	Wroclaw
Spain	Hosp. Univ. Vall D Hebron	Barcelona
Spain	Hosp. Univ. Infanta Leonor	Madrid
Spain	Hosp. Univ. Marques de Valdecilla	Santander
Spain	Hosp. Alvaro Cunqueiro	Vigo
Taiwan	National Cheng Kung University Hospital	Tainan
United States	I.D. Care, Inc.	Hillsborough	New Jersey

Sponsors (1)

Lead Sponsor	Collaborator
Janssen Research & Development, LLC

Countries where clinical trial is conducted

United States,  Canada,  Japan,  Poland,  Spain,  Taiwan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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])	Percentage of participants with a reduction of at least 2log10 IU/mL in HBsAg levels from baseline at Week 24 (EOSI) were planned to be reported.	Week 24
Secondary	Percentage of Participants With Adverse Events (AEs)	An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship.	Up to 1 month 26 days
Secondary	Percentage of Participants With Serious Adverse Events (SAEs)	An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. SAE is any untoward medical occurrence that at any dose may result in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, is a suspected transmission of any infectious agent via a medicinal product.	Up to 1 month 26 days
Secondary	Percentage of Participants With Abnormalities in Clinical Laboratory Tests	Percentage of participants with abnormalities in clinical laboratory tests including hematology, blood coagulation, blood biochemistry, urinalysis, urine chemistry, renal biomarkers, were reported.	Up to 1 month 26 days
Secondary	Percentage of Participants With Abnormalities in 12-Lead Electrocardiograms (ECGs)	Percentage of participants with abnormalities in 12-Lead ECGs were reported.	Up to 1 month 26 days
Secondary	Percentage of Participants With Abnormalities in Vital Signs	Percentage of participants with abnormalities in vital signs were reported.	Up to 1 month 26 days
Secondary	Percentage of Participants With Abnormalities in Ophthalmologic Examination	Percentage of participants with abnormalities in ophthalmologic examination were planned to be reported.	Weeks 8 and 20
Secondary	Percentage of Participants With Abnormalities in Physical Examination	Percentage of participants with abnormalities in physical examination were planned to be reported.	Week 24
Secondary	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	Percentage of participants meeting the protocol-defined NA treatment completion criteria based on the Week 24 (EOSI) or follow-up Week 2 visits was planned to be reported. NA treatment completion criteria were as follows: (a) participant had alanine transaminase (ALT) <3*upper limits of normal (ULN); (b) participant had Hepatitis B Virus (HBV) Deoxyribonucleic acid (DNA) <20 international units per milliliter (IU/mL); (c) participant was Hepatitis B e antigen (HBeAg)-negative; (d) participant had Hepatitis B surface antigen (HBsAg<10 IU/mL.	Week 24 (EOSI) and follow-up Week 2
Secondary	Percentage of Participants With HBsAg Seroclearance at Follow-up Weeks 24 and 48 Without Re-starting NA Treatment	Percentage of participants with HBsAg seroclearance at follow-up Weeks 24 and 48 without re-starting NA treatment were planned to be reported. Seroclearance of HBsAg is defined as a (quantitative) HBsAg level	Follow-up Weeks 24 and 48
Secondary	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	Percentage of participants with HBV DNA	Follow-up Weeks 24 and 48
Secondary	Percentage of Participants With Virologic Flares	Percentage of participants with virologic flares were reported. The start of a confirmed virologic flare is defined as the first date of two consecutive visits with HBV DNA >200 IU/mL. The end date of the same confirmed virologic flare is defined as the first date when HBV DNA value returns to less than or equal to (<=)200 IU/mL or the date of NA treatment restart, whichever comes first.	Up to 1 month 26 days
Secondary	Percentage of Participants With Biochemical Flares	Percentage of participants with biochemical flares were reported. The start date of a confirmed off-treatment biochemical flare: the first date of two consecutive visits with ALT and/or AST>=3x ULN and >=3x off-treatment/on-treatment nadir (that is, lowest value observed during off-treatment period up to the time point of meeting the biochemical flare criteria) while the participant does not receive any of the study interventions. The end date of the same off-treatment/on-treatment biochemical flare: the first date when there is a 50% reduction from the peak ALT and/or AST level & <3x ULN.	Up to 1 month 26 days
Secondary	Percentage of Participants Requiring Nucleos(t)Ide Analog (NA) Re-treatment	Percentage of participants requiring NA re-treatment were planned to be reported.	Up to 72 weeks
Secondary	Percentage of Participants With HBsAg, Hepatitis B e Antigen (HBeAg), HBV DNA, and Alanine Aminotransferase (ALT) Levels Below/Above Different Cut-offs	Percentage of participants with HBsAg, HBeAg, HBV DNA, and ALT levels below/above different cut-offs were planned to be reported.	Up to 72 weeks
Secondary	Percentage of Participants With HBsAg Seroconversion	Percentage of participants with HBsAg seroconversion were planned to be reported. Seroconversion of HBsAg is defined as having achieved HBsAg seroclearance (quantitative HBsAg level	Up to 72 weeks
Secondary	Change From Baseline in HBsAg Over Time	Change from baseline in HBsAg over time were planned to be reported.	Baseline up to Week 72
Secondary	Time to Achieve HBsAg Seroclearance	Time to achieve HBsAg seroclearance were planned to be reported. Time to achieve HBsAg seroclearance is defined as the number of days between the date of first study intervention intake and the date of the first occurrence of HBsAg seroclearance (that is, the date of the first HBsAg seroclearance - the date of first study intervention intake + 1). Seroclearance of HBsAg is defined as a (quantitative) HBsAg level	Up to 72 weeks
Secondary	Time to Achieve HBsAg Seroconversion	Time to achieve HBsAg seroconversion were planned to be reported. Time to achieve HBsAg seroconversion is defined as the number of days between the date of first study intervention intake and the date of the first occurrence of HBsAg seroclearance and appearance of anti-HBs antibodies (that is, the date of the first HBsAg seroclearance and anti-HBs antibodies - the date of first study intervention intake + 1). Seroconversion of HBsAg is defined as having achieved HBsAg seroclearance (quantitative HBsAg level	Up to 72 weeks
Secondary	Time to Achieve HBV DNA <Lower Limit of Quantitation (LLOQ)	Time to achieve HBV DNA	Up to 72 weeks
Secondary	Percentage of Participants With Virologic Breakthrough	Percentage of participants with virologic breakthrough were planned to be reported. HBV virological breakthrough is defined as having a confirmed on-treatment HBV DNA increase by >1 log10 from nadir level (lowest level reached during treatment) in participants who did not have on-treatment HBV DNA level below the LLOQ or a confirmed on-treatment HBV DNA level >200 IU/mL in participants who had on-treatment HBV DNA level below the LLOQ. LLOQ is 0.05 IU/mL.	Up to Week 24
Secondary	Serum Concentration of JNJ-73763989 (JNJ-73763924 and JNJ-73763976)	Serum concentration of JNJ-73763989 (JNJ-73763924 and JNJ-73763976) were planned to be reported.	Up to 72 weeks
Secondary	Serum Concentration of Nucleos(t)Ide Analog (NA) (Entecavir [ETV])	Serum concentration of NA (ETV) was planned to be reported.	Up to 72 weeks
Secondary	Serum Concentration of PegIFN-alpha-2a	Serum concentration of PegIFN-alpha-2a was planned to be reported.	Up to 72 weeks