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
complete
ID: NCT04439539
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.
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
Timeline
September 14, 2020
Start Date
February 13, 2024
End Date
Trial Details
Start date:
September 14, 2020
End date:
February 23, 2024
complete
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
ID: NCT04439539
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).
A Phase 1, Single-Dose, Open-Label, Parallel-Group Study to Evaluate the Effect of Hepatic Impairment on the Pharmacokinetics of JNJ-73763989
Hepatitis B
complete
ID: NCT04208386
The purpose of the study is to evaluate the single-dose pharmacokinetic (PK) of JNJ-73763976 and JNJ-73763924 following a subcutaneous (SC) injection of JNJ-73763989 (JNJ-3989) in participants with liver cirrhosis and various degrees of impaired hepatic function when compared with healthy participants with normal hepatic function and no liver cirrhosis.
Inclusion Criteria
For all participants: Body mass index (BMI) between 18.0 and 38 kilogram per meter square (kg/m^2), (extremes included), and a body weight not less than 50 kilograms (kg) at screening; Woman of childbearing potential must not be pregnant; Highly effective contraceptive measures in place for female participants of childbearing potential or male participants with female partners of childbearing potential; Non-smoker or light smoker as defined per protocol
For Healthy Participants with Normal Hepatic Function and No Liver Cirrhosis: Demographically comparable to the study groups with hepatic impairment with respect to sex, age (+/-10 years), and body weight (+/-10 kg); Participants must be in good health clinically and biologically as defined per protocol
For Participants with Liver Cirrhosis and Moderate or Mild or Severe Hepatic Impairment: Must have a total Child-Pugh score of 5 or 6, inclusive (mild); or 7 to 9, inclusive (moderate); or 10 to 15, inclusive (severe) as determined by the investigator; Must have liver cirrhosis with fibro scan readout greater than (>) 12.5 Kilopascal (kPa) as cut-off at screening
Participants with controlled hypertension, with problems directly associated with the primary diagnosis of hepatic impairment may be included. Participants may have concurrent stable medical conditions and may be included in the study if the investigator and the sponsor consider that the condition(s) will not introduce an additional risk factor and will not interfere with the study objectives and the procedures (that is, participants with mild degenerative joint disease, controlled diabetes, controlled thyroid conditions, other conditions addressed on a case by case basis)
Concomitant medications to treat underlying disease states or medical conditions related to hepatic impairment are allowed
Timeline
N/A
Start Date
July 20, 2020
End Date
complete
A Phase 1, Single-Dose, Open-Label, Parallel-Group Study to Evaluate the Effect of Hepatic Impairment on the Pharmacokinetics of JNJ-73763989
Hepatitis B
ID: NCT04208386
The purpose of the study is to evaluate the single-dose pharmacokinetic (PK) of JNJ-73763976 and JNJ-73763924 following a subcutaneous (SC) injection of JNJ-73763989 (JNJ-3989) in participants with liver cirrhosis and various degrees of impaired hepatic function when compared with healthy participants with normal hepatic function and no liver cirrhosis.
A Study of JNJ 73763989+JNJ 56136379+Nucleos(t)Ide Analog (NA) Regimen Compared to NA Alone in e Antigen Negative Virologically Suppressed Participants With Chronic Hepatitis B Virus Infection
Hepatitis B
complete
ID: NCT04129554
Hepatitis B virus (HBV) is a small deoxyribonucleic acid (DNA) virus that infects the liver and can cause either acute or chronic infection. It consists of a so-called nucleocapsid in which viral DNA is packed with hepatitis B core protein (HBc) and membranous envelope containing hepatitis B surface antigen (HBsAg). Chronic HBV infection may lead to serious illnesses like cirrhosis and hepatocellular carcinoma (HCC). Oral treatment with NAs is effective at suppressing viral DNA formation and lowering virus concentration in blood to levels below lower limit of quantification (LLOQ). JNJ-73763989 is a liver-targeted antiviral therapeutic for subcutaneous injection designed to treat chronic HBV infection via ribonucleic acid interference mechanism but rarely lead to functional cure defined as sustained loss of HBs Ag and HBV DNA in serum. JNJ-56136379 is an orally administered capsid assembly modulator that is being developed for treatment of chronic HBV infection. The aim of study is to evaluate efficacy of 48-week study intervention with JNJ-3989+JNJ-6379+NA regimen compared to NA alone, assessed by HBsAg seroclearance at Week 72 (i.e., 24 weeks after completion of all study interventions at Week 48) without restarting NA treatment in HBeAg negative virologically suppressed chronic hepatitis B (CHB) infected participants who received NA treatment for at least 2 years prior to screening. The study will be 2.3 years and will be conducted in 3 phases: a screening phase (4 weeks), a study intervention phase (48 weeks), and a follow-up phase (48 weeks). Safety will be evaluated by AEs including AEs of special interest to any of the study interventions, clinical laboratory tests, ECGs, vital signs, and physical examinations.
Inclusion Criteria
Medically stable based on physical examination, medical history, vital signs, electrocardiogram (ECG) at screening
Chronic hepatitis B virus (HBV) infection with documentation at least 6 months prior to screening
Hepatitis B e (antigen) (HBeAg)-negative on stable nucleotide analogue (NA) treatment for at least 24 months prior to screening
Hepatitis B surface antigen (HBsAg) greater than (>) 100 International Units per Milliliter (IU/mL) at screening
Body mass index (BMI) between 18.0 and 35 kilogram per meter square (kg/m^2), extremes included
Highly effective contraceptive measures in place for female participants of childbearing potential or male participants with female partners of childbearing potential
Liver fibrosis stage 0-2 (Metavir) or Fibroscan less than (<) 9 Kilopascal (kPa) at screening
Timeline
N/A
Start Date
June 9, 2022
End Date
complete
A Study of JNJ 73763989+JNJ 56136379+Nucleos(t)Ide Analog (NA) Regimen Compared to NA Alone in e Antigen Negative Virologically Suppressed Participants With Chronic Hepatitis B Virus Infection
Hepatitis B
ID: NCT04129554
The purpose of this study is to evaluate the efficacy of 48-week study intervention with JNJ-73763989+JNJ-56136379+nucleos(t)ide analog (NA) regimen compared to NA alone assessed by HBsAg levels. This study is part of HepB Wings Platform Trial (PLATFORMPAHPB2001).
A Double-blind, Placebo-controlled, Randomized, Parallel, Single Dose Study to Investigate Pharmacokinetics, Safety, and Tolerability of JNJ-73763989 in Healthy Japanese Adult Participants
Hepatitis B
complete
ID: NCT04002752
The purpose of this study is to investigate the pharmacokinetics, safety, and tolerability of JNJ-73763989 in healthy Japanese adult participants following single-dose subcutaneous administration of 3 different doses of JNJ-73763989, Dose Level 1 (Panel A), Dose Level 2 (Panel B) or Dose Level 3 (Panel C).
Inclusion Criteria
Participant must be a Japanese participant who has resided outside Japan for no more than 10 years and whose parents and grandparents are Japanese, as determined by participant's verbal report
Participant must have a body mass index (BMI; weight in kilogram [kg] divided by the square of height in meters) of 18.0 to 30.0 kilogram per square meter (kg/m^2) extremes included, and body weight not less than 45.0 kg
Participant must be healthy on the basis of physical examination, clinical laboratory tests, medical history, and vital signs performed at screening. In case of abnormalities (except for those listed in the exclusion criteria) a participant may be included after all if the investigator judges the abnormalities not clinically significant or appropriate and reasonable for the population under study. This determination must be recorded in the participant's source documents and initialed by the investigator
A female participant of childbearing potential must have a negative highly sensitive serum (beta-human chorionic gonadotropin [beta-hCG]) at screening and a negative urine pregnancy test on Day -1
A male participant must agree not to donate sperm after enrollment (Day 1) in the study until at least 90 days after receiving the study drug
Timeline
July 4, 2019
Start Date
August 23, 2019
End Date
Trial Details
End date:
August 23, 2019
complete
A Double-blind, Placebo-controlled, Randomized, Parallel, Single Dose Study to Investigate Pharmacokinetics, Safety, and Tolerability of JNJ-73763989 in Healthy Japanese Adult Participants
Hepatitis B
ID: NCT04002752
The purpose of this study is to investigate the pharmacokinetics, safety, and tolerability of JNJ-73763989 in healthy Japanese adult participants following single-dose subcutaneous administration of 3 different doses of JNJ-73763989, Dose Level 1 (Panel A), Dose Level 2 (Panel B) or Dose Level 3 (Panel C).
A Study to Assess Intrahepatic and Peripheral Changes of Immunologic and Virologic Markers in Chronic Hepatitis B Virus Infection (INSIGHT)
Hepatitis B
complete
ID: NCT04585789
The title of protocol reflects the original study design. The study design section is reflecting that the design as of protocol amendment 5 is non-randomized.
Inclusion Criteria
Medically stable on the basis of physical examination, medical history, vital signs, and triplicate 12-lead electrocardiogram (ECG) performed at screening
Hepatitis B virus (HBV) infection with documentation at least 6 months prior to screening: participants be either currently not treated with HBeAg positive status or virologically (nucleos[t]ide analog [NA]) suppressed with HBeAg negative status
Hepatitis B surface antigen (HBsAg) greater than (>) 100 International Units per Milliliter (IU/mL) at screening
Body mass index (BMI) between 18.0 and 35.0 kilogram per meter square (kg/m^2), extremes included
Highly effective contraceptive measures in place for female participants of childbearing potential or male participants with female partners of childbearing potential
Fibroscan liver stiffness measurement less than and equal to (<=) 9 Kilopascal (kPa) within 6 months prior to screening or at the time of screening
Timeline
March 11, 2021
Start Date
January 9, 2024
End Date
Trial Details
Start date:
March 11, 2021
End date:
January 9, 2024
Eligibility criteria:
18 Years to 65 Years (Adult, Older Adult)
complete
A Study to Assess Intrahepatic and Peripheral Changes of Immunologic and Virologic Markers in Chronic Hepatitis B Virus Infection (INSIGHT)
Hepatitis B
ID: NCT04585789
The purpose of this study is to assess changes in intrahepatic hepatitis B surface antigen (HBsAg) between baseline and on-treatment liver biopsy in response to JNJ-3989-based combination treatment.
A Study of JNJ-73763989 + Nucleos(t)Ide Analog in Participants Co-Infected With Hepatitis B and Hepatitis D Virus (REEF-D)
Hepatitis B
active
ID: NCT04535544
JNJ-73763989 is a liver-targeted antiviral therapeutic for subcutaneous injection designed to treat chronic hepatitis B virus (HBV) infection via ribonucleic acid interference mechanism. This phase 2 study is designed to evaluate safety and efficacy of JNJ-73763989 in HBV infected patients who are co-infected with HDV. The study consists of 2 parts: Part 1 will evaluate safety, tolerability and antiviral activity of JNJ-73763989 + NA while Part 2 will evaluate the safety and efficacy of the JNJ-73763989 + NA regimen in the treatment of HBV/HDV co-infection. Each part includes 3 phases: Screening phase (from 4 Week up to maximum of 8 weeks), Intervention phase (144 Week for Arm A and 148 Week for Arm B) and Follow-up phase (48 Week). The duration of individual study participation will be between 196 and 204 weeks. Safety and tolerability (including adverse events [AEs] and Serious AEs, laboratory assessments, electrocardiogram [ECG], vital signs, physical examination), efficacy (including HDV ribonucleic acid [RNA], HBV deoxyribonucleic acid [DNA] and antigens) , and pharmacokinetics will be assessed throughout the study.
Inclusion Criteria
Medically stable based on physical examination, medical history, vital signs, electrocardiogram (ECG) at screening
Chronic hepatitis B virus (HBV) and hepatitis D virus (HDV) co-infection with documentation at least 6 months prior to screening
For Part 1: hepatitis D RNA (HDV RNA) greater than or equal to (>=) 1000 international units per milliliter (IU/mL) at screening. For Part 2: must have HDV RNA values >= 500 IU/mL, and must have hepatitis B surface antigen (HBsAg) values less than or equal to (<=) 10000 IU/mL at screening or HDV RNA values at screening are <= 100000 IU/mL
Alanine aminotransferase (ALT) greater than upper limit normal (ULN) but less than 10 times (ULN)
Body mass index (BMI) between 18.0 and 35.0 kilogram per meter square (kg/m^2), extremes included
Highly effective contraceptive measures in place for female participants of childbearing potential or male participants with female partners of childbearing potential
Non-cirrhotic participants and participants with compensated cirrhosis (Child Pugh class A) at screening (Part 1) and participants must have absence of cirrhosis and platelet count of >= 140000 per deciliter (dL) for enrollment into Part-2
Timeline
September 17, 2020
Study start date
October 16, 2023
Study completion date
Trial Details
Start date:
September 17, 2020
End date:
October 16, 2023
Eligibility criteria:
18 Years to 65 Years (Adult, Older Adult)
active
A Study of JNJ-73763989 + Nucleos(t)Ide Analog in Participants Co-Infected With Hepatitis B and Hepatitis D Virus (REEF-D)
Hepatitis B
ID: NCT04535544
The purpose of the study is to evaluate on-treatment efficacy against hepatitis D virus (HDV) of JNJ-73763989 + nucleos(t)ide analog (NA) regimen compared to NA alone.
A Study of JNJ-73763989 in Healthy Chinese Adult Participants
Hepatitis B
complete
ID: NCT04586439
The purpose of the study is to evaluate the single-dose Pharmacokinetics of JNJ-73763976 and JNJ-73763924 following a subcutaneous (SC) injection of JNJ-73763989 (JNJ-3989) in healthy Chinese adult participants at 2 different doses, Dose 1 (Panel A) or Dose 2 (Panel B).
Inclusion Criteria
Participant must be healthy based on physical examination, laboratory assessment, vital signs and electrocardiogram (ECG) at screening
A female participant of childbearing potential must have a negative highly sensitive serum (beta-human chorionic gonadotropin [hCG]) pregnancy test at screening and a negative urine pregnancy test on Day -1
A male participant must agree not to donate sperm after enrollment (Day 1) in the study and a female participant must agree not to donate eggs (ova, oocytes) during the study until at least 90 days after receiving the study drug
Participant must not use nicotine-containing substances including tobacco products for at least 3 months prior to screening until completion of the study
Participant must have suitable veins for cannulation and/or repeated venipuncture
Timeline
N/A
Study start date
February 18, 2021
Study Completion date
Trial Details
End date:
February 18, 2021
Eligibility criteria:
18 Years to 55 Years (Adult)
complete
A Study of JNJ-73763989 in Healthy Chinese Adult Participants
Hepatitis B
ID: NCT04586439
The purpose of the study is to evaluate the single-dose Pharmacokinetics of JNJ-73763976 and JNJ-73763924 following a subcutaneous (SC) injection of JNJ-73763989 (JNJ-3989) in healthy Chinese adult participants at 2 different doses, Dose 1 (Panel A) or Dose 2 (Panel B).
A Study of Different Combination Regimens Including JNJ-73763989 and/or JNJ-56136379 for the Treatment of Chronic Hepatitis B Virus Infection (REEF-1)
Hepatitis B
complete
ID: NCT03982186
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 ribonucleic acid interference mechanism. JNJ-56136379 is an orally administered capsid assembly modulator that is being developed for the treatment of chronic HBV infection. The aim of the study is to evaluate efficacy as measured by proportion of participants who completed 48-week study intervention and qualified for stopping NA treatment at Week 48. The study includes: Screening phase (4 weeks), Double-blind study intervention phase (from Day 1 up to Week 48), and Follow-up phase (48 weeks after end of investigational intervention with a maximum duration of 96 weeks). The duration of individual study participation will be between 100 and 150 weeks. Safety and tolerability (including adverse events [AEs] and Serious AEs, laboratory assessments, electrocardiogram [ECG], vital signs, physical examination), efficacy (including HBsAg seroclearance), and pharmacokinetics will be assessed throughout the study.
Inclusion Criteria
Medically stable based on physical examination, medical history, vital signs, electrocardiogram (ECG) at screening
Chronic hepatitis B virus (HBV) infection with documentation at least 6 months prior to screening
Hepatitis B surface antigen (HBsAg) greater than (>) 100 International Units per Milliliter (IU/mL) at screening
Body mass index (BMI) between 18.0 and 35.0 kilogram per meter square (kg/m^2), extremes included
Highly effective contraceptive measures in place for female participants of childbearing potential or male participants with female partners of childbearing potential
Liver fibrosis stage 0-2 (Metavir) or Fibroscan less than (<) 9 Kilopascal (kPa) at screening
Timeline
March 29, 2021
Study start date
April 26, 2022
Study completion date
Trial Details
Start date:
March 29, 2021
Eligibility criteria:
18 Years to 65 Years (Adult, Older Adult)
complete
A Study of Different Combination Regimens Including JNJ-73763989 and/or JNJ-56136379 for the Treatment of Chronic Hepatitis B Virus Infection (REEF-1)
Hepatitis B
ID: NCT03982186
The purpose of this study is to establish the dose-response relationship for antiviral activity of 3 dose levels of JNJ-73763989+nucleos(t)ide analog (NA) and to evaluate the efficacy of combination regimens of JNJ-73763989+NA (with and without JNJ-56136379) and of JNJ-56136379+NA.
A Phase 1 Clinical Study to Investigate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics Effects of a Single Dose of VSA001 Injection in Chinese Healthy Adult Volunteers
planned
ID: NCT05757596
This is a phase 1, randomized, double-blind, placebo-controlled, parallel-group study to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics effects of a single dose of VSA001 injection in Chinese healthy adult volunteers. Eligible enrolled participants will initially receive VSA001 injection at the assigned dose level.
Inclusion Criteria
The subjects voluntarily participate in this study who are able to read, understand, and sign the ICF before participation; and have a full understanding of the content, process and possible adverse reactions of the study and are able to complete the study in accordance with the requirements of the protocol.
Healthy male and female subjects aged between 18 and 55 years (both inclusive) at the time of informed consent.
Body mass index (BMI) = weight (kg)/height (m)2, within the range of 19.0-30.0 kg/m2 (both inclusive), and body weight no less than 50 kg.
In good general health and without clinically significant abnormalities as judged by the investigator, based on medical history, physical examination, vital signs, 12-lead ECG, and laboratory results.
Negative serum pregnancy test within 72 h prior to initiation of study treatment in all premenopausal females and females who have been amenorrheic for less than 12 months. (Serum pregnancy test is not required for females who have undergone surgical sterilization, such as hysterectomy and/or bilateral oophorectomy, or those who have not experienced menses for 12 consecutive months and are judged to be postmenopausal based on factors such as age and castration therapy).
Subjects and their partners must agree to use adequate contraceptive methods prior to initiation of study treatment, during the study, and for at least 3 months after discontinuation of study treatment.
Fasting serum TGs >80 mg/dL (>0.903 mmol/L) at screening.
Trial Details
Eligibility criteria:
18 Years to 55 Years (Adult), All Sexes, Accepts Healthy Volunteers
planned
A Phase 1 Clinical Study to Investigate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics Effects of a Single Dose of VSA001 Injection in Chinese Healthy Adult Volunteers
ID: NCT05757596
This is a phase 1, randomized, double-blind, placebo-controlled, parallel-group study to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics effects of a single dose of VSA001 injection in Chinese healthy adult volunteers. Eligible enrolled participants will initially receive VSA001 injection at the assigned dose level.
A Phase I, Randomized, Double-Blind, Placebo-Controlled, Dose-Escalating Study to Evaluate the Safety, Tolerability and Pharmacokinetics of ARC-520 in Normal Adult Volunteers
complete
ID: NCT01872065
The purpose of this study is to evaluate the safety, tolerability and pharmacokinetics of ARC-520 in normal, adult volunteers.
Inclusion Criteria
Healthy male or female subjects, 18-55 years of age
Be a non-smoker
Trial Details
Eligibility criteria:
18 Years to 55 Years (Adult), All Sexes, Accepts Healthy Volunteers
complete
A Phase I, Randomized, Double-Blind, Placebo-Controlled, Dose-Escalating Study to Evaluate the Safety, Tolerability and Pharmacokinetics of ARC-520 in Normal Adult Volunteers
ID: NCT01872065
The purpose of this study is to evaluate the safety, tolerability and pharmacokinetics of ARC-520 in normal, adult volunteers.