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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT04585789




Registration number
NCT04585789
Ethics application status
Date submitted
9/10/2020
Date registered
14/10/2020
Date last updated
5/03/2024

Titles & IDs
Public title
A Study to Assess Intrahepatic and Peripheral Changes of Immunologic and Virologic Markers in Chronic Hepatitis B Virus Infection
Scientific title
A Phase 2 Randomized, Open-label, Parallel-group, Multicenter Study to Assess Intrahepatic and Peripheral Changes of Immunologic and Virologic Markers in Response to Combination Regimens Containing JNJ-73763989 and Nucleos(t)Ide Analog With or Without JNJ-56136379 in Patients With Chronic Hepatitis B Virus Infection
Secondary ID [1] 0 0
2019-004475-39
Secondary ID [2] 0 0
CR108790
Universal Trial Number (UTN)
Trial acronym
INSIGHT
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Hepatitis B 0 0
Condition category
Condition code
Infection 0 0 0 0
Other infectious diseases
Oral and Gastrointestinal 0 0 0 0
Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - JNJ-73763989
Treatment: Drugs - JNJ-56136379
Treatment: Drugs - Entecavir (ETV)
Treatment: Drugs - Tenofovir disoproxil
Treatment: Drugs - Tenofovir alafenamide (TAF)
Treatment: Drugs - PegIFN-alpha-2a (Optional)

Experimental: Panel 1: JNJ-73763989+ NA - Ongoing and new participants will receive JNJ-73763989 subcutaneous (SC) injection once every 4 weeks (last injection at Week 44) and nucleos(t)ide analog (NA) treatment (either entecavir \[ETV\], tenofovir disoproxil or tenofovir alafenamide \[TAF\] tablets) once daily up to 48 weeks. Participants may receive optional treatment with pegylated interferon alpha-2a (PegIFN-alpha-2a) after the Week 40 for a duration of either 12 or 24 weeks at the investigator's discretion. As per amendment-5, JNJ-56136379 is no longer included as part of the study intervention and all participants are counted as single arm in each panel.

Experimental: Panel 2: JNJ-73763989+ NA - Ongoing and new participants will receive JNJ-73763989 SC injection once every 4 weeks (last injection at Week 44) and NA treatment (ETV, tenofovir disoproxil or TAF tablets) once daily up to 48 weeks. Participants may receive optional treatment with PegIFN-alpha-2a after the Week 40 for a duration of either 12 or 24 weeks at the investigator's discretion. As per amendment-5, JNJ-56136379 is no longer included as part of the study intervention and all participants are counted as single arm in each panel.


Treatment: Drugs: JNJ-73763989
JNJ-73763989 will be administered subcutaneously once every 4 weeks up to Week 44.

Treatment: Drugs: JNJ-56136379
JNJ-56136379 tablets will be administered orally once daily up to 48 weeks.

Treatment: Drugs: Entecavir (ETV)
ETV tablet will be administered orally once daily up to 48 weeks as NA treatment.

Treatment: Drugs: Tenofovir disoproxil
Tenofovir disoproxil will be administered orally once daily up to 48 weeks as NA treatment.

Treatment: Drugs: Tenofovir alafenamide (TAF)
TAF will be administered orally once daily up to 48 weeks as NA treatment.

Treatment: Drugs: PegIFN-alpha-2a (Optional)
PegIFN-alpha-2a injection will be administered subcutaneously once weekly after Week 40 for either 12 or 24 weeks.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Panel 1 and 2: Absolute Change From Baseline in the Percentage of Hepatitis B Surface Antigen (HBsAg) Hepatocytes at Week 40
Timepoint [1] 0 0
Baseline, Week 40
Secondary outcome [1] 0 0
Panel 1 and 2: Change From Baseline in Intrahepatic Immune Response
Timepoint [1] 0 0
Baseline, Week 40
Secondary outcome [2] 0 0
Panel 1 and 2: Change From Baseline in Intrahepatic Viral Parameters: HBsAg and Hepatitis B Virus (HBV) Deoxyribonucleic Acid (DNA)
Timepoint [2] 0 0
Baseline, Week 40
Secondary outcome [3] 0 0
Panel 1 and 2: Change From Baseline in Intrahepatic Covalently Closed Circular DeoxyriboNucleic Acid (cccDNA) and Pre-genomic RiboNucleic Acid (pgRNA) Levels
Timepoint [3] 0 0
Baseline, Week 40
Secondary outcome [4] 0 0
Panel 1 and 2: Percentage of Participants With HBsAg Seroclearance at Week 72 Without Restarting Nucleos(t)Ide Analog (NA)Treatment
Timepoint [4] 0 0
Week 72 (extended follow-up, ie, 24 weeks after completion of all study interventions at Week 48)
Secondary outcome [5] 0 0
Panel 1 and 2: Percentage of Participants With (Sustained) Reduction, Suppression, and/or Seroclearance
Timepoint [5] 0 0
Up to Week 120 (included participants who received optional PegIFN-alpha-2a)
Secondary outcome [6] 0 0
Panel 1 and 2: Percentage of Participants With HBsAg and Hepatitis B e Antigen (HBeAg) Seroconversion
Timepoint [6] 0 0
Up to Week 120 (included participants who received optional PegIFN-alpha-2a)
Secondary outcome [7] 0 0
Panel 1 and 2: Percentage of Participants With Flares
Timepoint [7] 0 0
Up to Week 120 (included participants who received optional PegIFN-alpha-2a)
Secondary outcome [8] 0 0
Panel 1 and 2: Time to Achieve First HBsAg Seroclearance
Timepoint [8] 0 0
Up to Week 120 (included participants who received optional PegIFN-alpha-2a)
Secondary outcome [9] 0 0
Panel 1 and 2: Percentage of Participants With Virologic Breakthrough
Timepoint [9] 0 0
Up to Week 48
Secondary outcome [10] 0 0
Panel 1 and 2: Change From Baseline in HBV-Specific Peripheral Blood T-cell Responses During the Study Intervention and Follow-up Phases
Timepoint [10] 0 0
Baseline up to Week 48
Secondary outcome [11] 0 0
Panel 1 and 2: Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
Timepoint [11] 0 0
From Day 1 (Week 0) up to Week 120 (included participants who received optional PegIFN-alpha-2a)
Secondary outcome [12] 0 0
Panel 1 and 2: Percentage of Participants With Abnormalities in Selected Clinical Laboratory Tests, Electrocardiogram (ECG), Vital Signs And Physical Examination
Timepoint [12] 0 0
From Day 1 (Week 0) up to Week 120 (included participants who received optional PegIFN-alpha-2a)
Secondary outcome [13] 0 0
Panel 1 and 2: Plasma Concentration of JNJ-73763989 (JNJ-73763976 and JNJ-73763924) and Optionally of JNJ-56136379, NA and/or Pegylated Interferon Alpha-2a (PegIFN-alpha-2a)
Timepoint [13] 0 0
Panel 1 and 2: post-dose on Days 1, 29, 85, 169, 337

Eligibility
Key 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
Minimum age
18 Years
Maximum age
65 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Evidence of infection with hepatitis A, C, D or E virus infection or evidence of human immunodeficiency, virus type 1 (HIV-1) or HIV-2 infection at screening
* History or evidence of clinical signs/symptoms of hepatic decompensation including but not limited to: portal hypertension, ascites, hepatic encephalopathy, esophageal varices
* History or signs of cirrhosis or portal hypertension, signs of hepatocellular carcinoma (HCC) or clinically relevant renal abnormalities on an abdominal ultrasound performed within 6 months prior to screening or at the time of screening
* Presence of coagulopathy or bleeding disorder as indicated by: (a) International normalized ratio (INR) greater than or equal to (>=) 1.1* upper limit of normal (ULN); (b) Partial thromboplastin time >1.1*ULN; (c) Any signs of prolonged bleeding (>10 minutes)
* Presence of hemoglobinopathy (including sickle cell disease, thalassemia)
* Liver biopsy performed prior to screening that led to complications and that in the opinion of the investigator would prohibit another liver biopsy

Study design
Purpose of the study
Other
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
11/03/2021
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
9/01/2024
Sample size
Target
Accrual to date
Final
24
Recruitment in Australia
Recruitment state(s)
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Maryland
Country [2] 0 0
Belgium
State/province [2] 0 0
Edegem
Country [3] 0 0
Canada
State/province [3] 0 0
Ontario
Country [4] 0 0
France
State/province [4] 0 0
Clichy
Country [5] 0 0
Germany
State/province [5] 0 0
Hamburg
Country [6] 0 0
Italy
State/province [6] 0 0
Milano
Country [7] 0 0
New Zealand
State/province [7] 0 0
Auckland
Country [8] 0 0
Poland
State/province [8] 0 0
Myslowice
Country [9] 0 0
United Kingdom
State/province [9] 0 0
London

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Janssen Research & Development, LLC
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
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.
Trial website
https://clinicaltrials.gov/study/NCT04585789
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Janssen Research & Development, LLC Clinical Trial
Address 0 0
Janssen Research & Development, LLC
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT04585789