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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT04667104




Registration number
NCT04667104
Ethics application status
Date submitted
9/12/2020
Date registered
14/12/2020
Date last updated
3/07/2024

Titles & IDs
Public title
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
Scientific 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
Secondary ID [1] 0 0
2020-003956-34
Secondary ID [2] 0 0
CR108928
Universal Trial Number (UTN)
Trial acronym
PENGUIN
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Hepatitis B, Chronic 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 - Tenofovir disoproxil
Treatment: Drugs - Tenofovir alafenamide (TAF)
Treatment: Drugs - Entecavir (ETV) monohydrate
Treatment: Drugs - PegIFN-alpha2a

Experimental: Treatment Period (TP) 1 (JNJ-73763989 + Nucleos(t)ide Analog)+ TP 2 (TP 1+PegIFN-alpha2a) - Participants will receive combination treatment with JNJ-73763989+ nucleos(t)ide analog (NA) for 12 weeks during Treatment Period 1 and the participants who meet the eligibility criteria for PegIFN-alpha2a at Week 12 will receive combination treatment with JNJ-73763989 + NA plus PegIFN-a2a for 12 weeks during Treatment Period 2.


Treatment: Drugs: JNJ-73763989
JNJ-73763989 injection will be administered subcutaneously once every 4 weeks.

Treatment: Drugs: Tenofovir disoproxil
Tenofovir disoproxil film-coated tablet will be administered orally once daily.

Treatment: Drugs: Tenofovir alafenamide (TAF)
TAF film-coated tablet will be administered orally once daily.

Treatment: Drugs: Entecavir (ETV) monohydrate
ETV monohydrate film-coated tablet will be administered orally once daily.

Treatment: Drugs: PegIFN-alpha2a
PegIFN-alpha2a injection will be administered subcutaneously once weekly.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
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
Assessment method [1] 0 0
Percentage of participants with a reduction of at least 2 log10IU/mL in HBsAg levels from baseline to Week 24 were reported. A responder was defined as a participant with reduction of at least 2 log10 IU/mL in HBsAg levels from baseline at Week 24.
Timepoint [1] 0 0
From Baseline (Day 1) to Week 24
Secondary outcome [1] 0 0
Percentage of Participants With Treatment Emergent Adverse Events (TEAEs) as a Measure of Safety and Tolerability
Assessment method [1] 0 0
Percentage of participants with TEAEs were reported. An adverse event (AE) was any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study. TEAEs were AEs with onset during the intervention period or follow-up period or that were a consequence of a pre-existing condition that had worsened since baseline.
Timepoint [1] 0 0
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)
Secondary outcome [2] 0 0
Percentage of Participants With Serious Adverse Events (SAEs) as a Measure of Safety and Tolerability
Assessment method [2] 0 0
An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study. TEAEs were AEs with onset during the intervention period or follow-up period or that were a consequence of a pre-existing condition that had worsened since baseline. A SAE is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly.
Timepoint [2] 0 0
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)
Secondary outcome [3] 0 0
Number of Participants With Clinically Significant Abnormalities in Vital Signs as a Measure of Safety and Tolerability
Assessment method [3] 0 0
Number of participants with clinically significant abnormalities in vital signs (pulse rate, and blood pressure \[systolic and diastolic\]) were reported.
Timepoint [3] 0 0
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)
Secondary outcome [4] 0 0
Number of Participants With Clinically Significant Abnormalities in Laboratory Findings as a Measure of Safety and Tolerability
Assessment method [4] 0 0
Number of participants with clinically significant abnormalities in laboratory findings (including hematology, blood biochemistry, and urinalysis) were reported. Only parameters in which any participant had abnormality are reported below.
Timepoint [4] 0 0
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)
Secondary outcome [5] 0 0
Number of Participants With Clinically Significant Abnormalities in 12-Lead Electrocardiogram (ECGs) as a Measure of Safety and Tolerability
Assessment method [5] 0 0
Number of participants with clinically significant abnormalities in 12- lead ECGs (heart rate, PR, QRS and QT corrected \[QTc\]) were reported.
Timepoint [5] 0 0
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
Secondary outcome [6] 0 0
Number of Participants With Clinically Significant Abnormalities in Physical Examination as a Measure of Safety and Tolerability
Assessment method [6] 0 0
Number of participants with clinically significant abnormalities in physical examination were reported.
Timepoint [6] 0 0
Treatment Period 1: From Baseline (Day 1) up to Week 12; Treatment Period 2: From Week 12 up to Week 24
Secondary outcome [7] 0 0
Number of Participants With Abnormalities in Ophthalmic Examination as a Measure of Safety and Tolerability
Assessment method [7] 0 0
Number of participants with abnormalities in Ophthalmic examination were planned to be reported.
Timepoint [7] 0 0
Treatment Period 1: From Baseline (Day 1) up to Week 12; Treatment Period 2: From Week 12 up to Week 24
Secondary outcome [8] 0 0
Percentage of Participants Meeting the Protocol-defined Nucleos(t)Ide Analog (NA) Treatment Completion Criteria at End of Study Intervention (EOSI)
Assessment method [8] 0 0
Percentage of participants meeting the protocol-defined NA treatment completion criteria at EOSI were reported. NA treatment completion criteria are defined based on laboratory results at Week 24 were; HBsAg \<10 IU/mL; HBeAg-negative; HBV DNA \<20 IU/mL, that is, lower limit of quantification(LLOQ); alanine aminotransferase(ALT) \<3\*ULN.
Timepoint [8] 0 0
At Week 24 (EOSI)
Secondary outcome [9] 0 0
Percentage of Participants With Hepatitis B e Antigen (HBeAg) Levels Below Different Cut-offs
Assessment method [9] 0 0
Percentage of participants with HBeAg levels below different cut-offs were reported. The cut-offs for HBeAg levels were as followed:\< 100 IU/mL, \< 10 IU/mL, \< 1 IU/mL, \< LLOQ (0.11 IU/mL).
Timepoint [9] 0 0
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)
Secondary outcome [10] 0 0
Percentage of Participants With HBsAg Levels Below Different Cut-offs
Assessment method [10] 0 0
Percentage of participants with HBsAg levels below different cut-offs were reported. The cut-offs for HBsAg level were: \<1000 IU/mL, \<100 IU/mL, \<10 IU/mL, \<1 IU/mL, \
Timepoint [10] 0 0
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)
Secondary outcome [11] 0 0
Percentage of Participants With Hepatitis B Virus (HBV) Deoxyribonucleic Acid (DNA) Levels Below Different Cut-offs
Assessment method [11] 0 0
Percentage of participants with HBV DNA levels below cut-offs were reported. The cut-offs for HBV DNA were as follows: \
Timepoint [11] 0 0
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)
Secondary outcome [12] 0 0
Percentage of Participants With ALT Levels Greater Than or Equal to (>=) 3*ULN
Assessment method [12] 0 0
Percentage of participants with ALT levels below \>=3\*ULN cut-off were reported.
Timepoint [12] 0 0
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)
Secondary outcome [13] 0 0
Percentage of Participants With HBeAg Seroconversion
Assessment method [13] 0 0
Percentage of participants with HBeAg seroconversion were reported. Seroconversion of HBeAg is defined as having achieved HBeAg seroclearance (as HBeAg level \
Timepoint [13] 0 0
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)
Secondary outcome [14] 0 0
Percentage of Participants With HBsAg Seroconversion
Assessment method [14] 0 0
Percentage of participants with HBsAg seroconversion were reported. Seroconversion of HBsAg was defined as having achieved HBsAg seroclearance (defined as HBsAg \
Timepoint [14] 0 0
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)
Secondary outcome [15] 0 0
Change From Baseline Over Time in HBsAg Levels
Assessment method [15] 0 0
Change from baseline over time in HBsAg levels were reported. The baseline assessment was defined as the last observed non-missing measurement before the date and time of the first administration of any of study agent.
Timepoint [15] 0 0
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)
Secondary outcome [16] 0 0
Change From Baseline Over Time in HBeAg Levels
Assessment method [16] 0 0
Change from baseline over time in HBeAg levels were reported. The baseline assessment was defined as the last observed non-missing measurement before the date and time of the first administration of any of study agent.
Timepoint [16] 0 0
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)
Secondary outcome [17] 0 0
Change From Baseline Over Time in HBV DNA Levels
Assessment method [17] 0 0
Change from baseline over time in HBV DNA levels were reported. The baseline assessment was defined as the last observed non-missing measurement before the date and time of the first administration of any of study agent.
Timepoint [17] 0 0
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)
Secondary outcome [18] 0 0
Time to First Occurrence of HBsAg Seroclearance
Assessment method [18] 0 0
Time to first occurrence of HBsAg seroclearance were reported in median time. Time to first occurrence of the HBsAg seroclearance was defined as the number of days between the date of first study intervention intake and the date of first occurrence of the HBsAg seroclearance.
Timepoint [18] 0 0
From Baseline (Day 1) up to follow-up Week 48 (with window period of +/- 4 days, that is Week 72.4)
Secondary outcome [19] 0 0
Time to First Occurrence of HBeAg Seroclearance
Assessment method [19] 0 0
Time to first occurrence of HBeAg seroclearance were reported in median time. Time to first occurrence of the HBeAg seroclearance is defined as the number of days between the date of first study intervention intake and the date of the first occurrence of the HBeAg seroclearance.
Timepoint [19] 0 0
From Baseline (Day 1) up to follow-up Week 48 (with window period of +/- 4 days, that is Week 72.4)
Secondary outcome [20] 0 0
Time to First Occurrence of HBV DNA < LLOQ
Assessment method [20] 0 0
Time to first occurrence of HBV DNA \< LLOQ (20 IU/mL) were reported in median time. Time to first occurrence of the HBV DNA \< LLOQ is defined as the number of days between the date of first study intervention intake and the date of the first occurrence of the HBV DNA \< LLOQ.
Timepoint [20] 0 0
From Baseline (Day 1) up to follow-up Week 48 (with window period of +/- 4 days, that is Week 72.4)
Secondary outcome [21] 0 0
Percentage of Participants With Virologic Breakthrough
Assessment method [21] 0 0
Percentage of Participants with virologic breakthrough were reported. It was defined as confirmed on-treatment (the time period during which the participant received any of the study treatments) HBV DNA increase by \>1 log10 IU/mL from nadir or confirmed on-treatment HBV DNA level \>200 IU/mL in participants who had HBV DNA level \
Timepoint [21] 0 0
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)
Secondary outcome [22] 0 0
Percentage of Participants With HBsAg Seroclearance at Week 48 Without Re-starting NA Treatment
Assessment method [22] 0 0
Percentage of participants with HBsAg seroclearance at Week 48 (i.e., 24 weeks after completion of all study interventions at Week 24) without re-starting NA treatment were reported. HBsAg seroclearance was defined as \[quantitative\] HBsAg \
Timepoint [22] 0 0
At Week 48 (24 weeks after completion of all study interventions at Week 24)
Secondary outcome [23] 0 0
Percentage of Participants With HBV DNA < LLOQ at Week 48 Without Re-starting NA Treatment
Assessment method [23] 0 0
Percentage of participants with HBV DNA \
Timepoint [23] 0 0
At Week 48 (24 weeks after completion of all study interventions at Week 24)
Secondary outcome [24] 0 0
Percentage of Participants With Biochemical Flares
Assessment method [24] 0 0
Percentage of participants with biochemical flares were reported. On-treatment biochemical flare was defined as confirmed ALT and/or AST \>=3\*ULN and \>=3\*nadir, while the participant received any of the study interventions. Off-treatment biochemical flare was defined as confirmed ALT and/or AST =3\*ULN and =3\*nadir, while the participants did not receive any of the study interventions (Off treatment, including NA).
Timepoint [24] 0 0
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)
Secondary outcome [25] 0 0
Percentage of Participants With Virologic Flares
Assessment method [25] 0 0
Percentage of participants with virologic flares were reported. Virologic flare was defined as confirmed HBV DNA \>peak threshold (lowest peak to qualify as virologic flare was HBV DNA \>200 IU/mL) in participants who were off-treatment. Off-treatment was defined as the time period after stopping all study treatments (including NA) and had HBV DNA \
Timepoint [25] 0 0
Follow-Up Period: From Week 24 up to follow-up Week 48 (with window period of +/- 4 days, that is Week 72.4)
Secondary outcome [26] 0 0
Number of Participants Requiring NA Re-treatment
Assessment method [26] 0 0
Number of participants requiring NA re-treatment based on failure in NA treatment completion criteria (HBsAg \<10 IU/mL, and HBeAg-negative, and HBV DNA \< LLOQ (20 IU/mL), and ALT \<3\*ULN) were reported.
Timepoint [26] 0 0
Follow-Up Period: From Week 24 up to follow-up Week 48 (with window period of +/- 4 days, that is Week 72.4)
Secondary outcome [27] 0 0
Maximum Observed Plasma Concentration (Cmax) of JNJ-73763989 (JNJ-73763976 and JNJ-73763924)
Assessment method [27] 0 0
The maximum observed plasma concentrations (Cmax) of JNJ-73763989 (JNJ-73763976 and JNJ-73763924) were reported.
Timepoint [27] 0 0
Treatment Period 1: Day 1 Week 1; Treatment Period 2: Day 1, Week 12
Secondary outcome [28] 0 0
Plasma Concentration 24 Hours After Administration (C24h) of JNJ-73763989 (JNJ-73763976 and JNJ-73763924)
Assessment method [28] 0 0
Plasma concentration 24 hours (C24h) after administration of JNJ-73763989 (JNJ-73763976 and JNJ-73763924) were reported.
Timepoint [28] 0 0
Treatment Period 1: Day 1 Week 1; Treatment Period 2: Day 1, Week 12
Secondary outcome [29] 0 0
Time to Reach Maximum Observed Plasma Concentration (Tmax) of JNJ-73763989 (JNJ-73763976 and JNJ-73763924)
Assessment method [29] 0 0
Time to reach maximum observed plasma concentration (Cmax) (Tmax) of JNJ-73763989 (JNJ-73763976 and JNJ-73763924) were reported.
Timepoint [29] 0 0
Treatment Period 1: Day 1, Week 1; Treatment Period 2: Day 1, Week 12
Secondary outcome [30] 0 0
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)
Assessment method [30] 0 0
Area under the plasma concentration versus time curve from time 0 to 24 hours (AUC\[0-24\]h) of JNJ-73763989 (JNJ-73763976 and JNJ-73763924) were reported.
Timepoint [30] 0 0
Treatment Period 1: Day 1, Week 1; Treatment Period 2: Day 1, Week 12

Eligibility
Key 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
Minimum age
18 Years
Maximum age
65 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Not applicable
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
Single group
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
1/02/2021
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
17/04/2023
Sample size
Target
Accrual to date
Final
48
Recruitment in Australia
Recruitment state(s)
Recruitment outside Australia
Country [1] 0 0
Japan
State/province [1] 0 0
Bunkyo Ku
Country [2] 0 0
Japan
State/province [2] 0 0
Suita-shi
Country [3] 0 0
New Zealand
State/province [3] 0 0
Auckland
Country [4] 0 0
New Zealand
State/province [4] 0 0
Papatoetoe
Country [5] 0 0
Poland
State/province [5] 0 0
Gdansk
Country [6] 0 0
Poland
State/province [6] 0 0
Myslowice
Country [7] 0 0
Poland
State/province [7] 0 0
Warszawa
Country [8] 0 0
Poland
State/province [8] 0 0
Wroclaw
Country [9] 0 0
Taiwan
State/province [9] 0 0
Kaohsiung
Country [10] 0 0
Taiwan
State/province [10] 0 0
Taichung
Country [11] 0 0
Taiwan
State/province [11] 0 0
Tainan

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

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
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
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement


What supporting documents are/will be available?



Results publications and other study-related documents

No documents have been uploaded by study researchers.

Results are available at https://clinicaltrials.gov/study/NCT04667104