Hepatitis D, Chronic
Conditions
Brief summary
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.
Interventions
DRUGJNJ-73763989
JNJ-73763989 will be administered as a SC injection.
DRUGPlacebo
Matching placebo to JNJ-73763989 will be administered as a SC injection.
ETV monohydrate film coated tablet will be administered orally.
DRUGTenofovir disoproxil
Tenofovir disoproxil film-coated tablet will be administered orally.
TAF film coated tablet will be administered orally.
Sponsors
Janssen Research & Development, LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
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
Exclusion criteria
* Evidence of infection with hepatitis A, C, 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 or any laboratory abnormalities indicating a reduced liver function as defined in the protocol * Evidence of liver disease of non-HBV/HDV etiology * Signs of hepatocellular carcinoma (HCC) * Significant laboratory abnormalities as defined in the protocol at screening * Participants with a history of malignancy within 5 years before screening * Abnormal sinus rhythm or ECG parameters at screening as defined in the protocol * History of or current cardiac arrhythmia or history or clinical evidence of significant or unstable cardiac disease * Participants with any current or previous illness for which, in the opinion of the investigator and/or sponsor, participation would not be in the best interest of the participant * History of or current clinically significant skin disease or drug rash * Participants with known allergies, hypersensitivity, or intolerance to JNJ-3989 or its excipients or excipients of the placebo content * Contraindications to the use of entecavir (ETV), tenofovir disoproxil, or tenofovir alafenamide (TAF) per local prescribing information * Participants who have taken any therapies disallowed per protocol * Female participants who are pregnant, or breast-feeding, or planning to become pregnant while enrolled in this study or within 90 days after the last dose of study intervention * Male participants who plan to father a child while enrolled * Participants who had or planned major surgery, (example, requiring general anesthesia) or who have received an organ transplant * Vulnerable participants (example, incarcerated individuals, individuals under a legal protection measure)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Double-blind:Part 1: Percentage of Participants With HDV Ribonucleic Acid (RNA) >=2 log10 IU/mL Decline From Baseline or HDV RNA Target Not Detected (TND) in Combination With Normal Alanine Aminotransferase (ALT) at Week 48 (Multiple Imputation Approach) | Week 48 | Percentage of participants with hepatitis D virus (HDV) RNA greater than or equal to (\>=) 2 log10 international units per milliliter (IU/mL) decline from baseline or HDV RNA TND in combination with normal ALT at Week 48 using multiple imputation approach was reported. TND was defined as no traces of HBV RNA were detected/found. Normal ALT was defined as ALT less than (\<) upper limit of normal (ULN) with ULN = 34 units per liter (U/L) for female and 43 U/L for male. 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 intervention on Day 1. The multiple imputation approach was derived using a longitudinal multiple regression model to impute missing data. |
| Double-blind: Part 2: Percentage of Participants With HDV RNA >=2 log10 IU/mL Decline From Baseline or HDV RNA TND in Combination With Normal ALT at Week 48 (Multiple Imputation Approach) | Week 48 | Percentage of participants with HDV RNA \>=2 log10 IU/mL decline from baseline or HDV RNA TND in combination with normal ALT at Week 48 using multiple imputation approach was reported. TND was defined as no traces of HBV RNA were detected/found. Normal ALT was defined as ALT \<ULN with ULN = 34 U/L for female and 43 U/L for male. 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 intervention on Day 1. The multiple imputation approach was derived using a longitudinal multiple regression model to impute missing data. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Parts 1 and 2: Percentage of Participants With HDV RNA >=2 log10 IU/mL Decline From Baseline or HDV RNA < Lower Limits of Quantification (LLOQ) at Week 48 | Week 48 | Percentage of participants with HDV RNA \>=2 log10 IU/mL decline from baseline or HDV RNA \< LLOQ at Week 48 was 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 intervention on Day 1. The multiple imputation approach was derived using a longitudinal multiple regression model to impute missing data. |
| Parts 1 and 2: Percentage of Participants With Normal ALT at Week 48 | Week 48 | Percentage of participants with normal ALT at Week 48 was reported. Normal ALT is defined as ALT \<ULN with ULN = 34 U/L for female and 43 U/L for male. The multiple imputation approach was derived using a longitudinal multiple regression model to impute missing data. |
| Parts 1 and 2: Percentage of Participants With Hepatitis B Surface Antigen (HBsAg) Seroclearance at Week 48 | Week 48 | Percentage of participants with HBsAg seroclearance at Week 48 was reported. HBsAg seroclearance was defined as HBsAg negativity (quantitative HBsAg level \<LLOQ) based on the assay used. |
| Parts 1 and 2: Percentage of Participants With >=2 Kilopascal (kPa) Reduction From Baseline in Liver Stiffness Measurement (LSM) Assessed by Vibration-controlled Transient Elastography (VCTE) (FibroScan) at Week 48 | Week 48 | Percentage of participants with \>=2 kPa reduction from baseline in LSM assessed by VCTE (fibroscan) at Week 48 was 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 intervention on Day 1. |
| Part 1: Percentage of Participants With HDV RNA >=2 log10 IU/mL Decline From Baseline or HDV RNA TND in Combination With Normal ALT | Week 48, FU Week 24 | Percentage of participants with HDV RNA \>=2 log10 IU/mL decline from baseline or HDV RNA TND in combination with normal ALT was reported. TND was defined as no traces of HBV RNA were detected/found. Normal ALT is defined as ALT \<ULN with ULN = 34 U/L for female and 43 U/L for male. 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 intervention on Day 1. The multiple imputation approach was derived using a longitudinal multiple regression model to impute missing data. |
| Part 2: Percentage of Participants With HDV RNA >=2 log10 IU/mL Decline From Baseline or HDV RNA TND in Combination With Normal ALT | Week 48, FU Week 24 | Percentage of participants with HDV RNA \>=2 log10 IU/mL decline from baseline or HDV RNA TND in combination with normal ALT was reported. TND was defined as no traces of HBV RNA were detected/found. Normal ALT is defined as ALT \<ULN with ULN = 34 U/L for female and 43 U/L for male. 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 intervention on Day 1. The multiple imputation approach was derived using a longitudinal multiple regression model to impute missing data. |
| Part 1: Percentage of Participants With HDV RNA >=2 log10 IU/mL Decline From Baseline in Combination With Normal ALT | Week 48 and FU Week 24 | Percentage of participants with HDV RNA \>=2 log10 IU/mL decline from baseline in combination with normal ALT was reported. Normal ALT is defined as ALT \<ULN with ULN = 34 U/L for female and 43 U/L for male. 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 intervention on Day 1. |
| Part 2: Percentage of Participants With HDV RNA >=2 log10 IU/mL Decline From Baseline in Combination With Normal ALT | Week 48 and FU Week 24 | Percentage of participants with HDV RNA \>=2 log10 IU/mL decline from baseline in combination with normal ALT was reported. Normal ALT is defined as ALT \<ULN with ULN = 34 U/L for female and 43 U/L for male. 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 intervention on Day 1. |
| Part 1: Percentage of Participants With HDV RNA TND in Combination With Normal ALT | Week 48 and FU Week 24 | Percentage of participants with HDV RNA TND in combination with normal ALT was reported. Normal ALT is defined as ALT \<ULN with ULN = 34 U/L for female and 43 U/L for male. TND was defined as no traces of HBV RNA were detected/found. The multiple imputation approach was derived using a longitudinal multiple regression model to impute missing data. |
| Part 2: Percentage of Participants With HDV RNA TND in Combination With Normal ALT | Week 48 and FU Week 24 | Percentage of participants with HDV RNA TND in combination with normal ALT was reported. TND was defined as no traces of HBV RNA were detected/found. Normal ALT was defined as ALT \<ULN with ULN = 34 U/L for female and 43 U/L for male. The multiple imputation approach was derived using a longitudinal multiple regression model to impute missing data. |
| Part 1: Percentage of Participants With HDV RNA >=2 log10 IU/mL Decline From Baseline or HDV RNA TND | Week 48 and FU Week 24 | Percentage of participants with HDV RNA \>=2 log10 IU/mL decline from baseline or HDV RNA TND was reported. TND was defined as no traces of HBV RNA were detected/found. 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 intervention on Day 1. |
| Part 2: Percentage of Participants With HDV RNA >=2 log10 IU/mL Decline From Baseline or HDV RNA TND | Week 48 and FU Week 24 | Percentage of participants with HDV RNA \>=2 log10 IU/mL decline from baseline or HDV RNA TND was reported. TND was defined as no traces of HBV RNA were detected/found. 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 intervention on Day 1. |
| Part 1: Percentage of Participants With HDV RNA >=2 log10 IU/mL Decline From Baseline | Week 48 and FU Week 24 | Percentage of participants with HDV RNA \>=2 log10 IU/mL decline from baseline was 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 intervention on Day 1. |
| Part 2: Percentage of Participants With HDV RNA >=2 log10 IU/mL Decline From Baseline | Week 48 and FU Week 24 | Percentage of participants with HDV RNA \>=2 log10 IU/mL decline from baseline was 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 intervention on Day 1. |
| Part 1: Percentage of Participants With HDV RNA TND | Week 48, FU Week 24 | Percentage of participants with HDV RNA TND was reported. TND was defined as no traces of HBV RNA were detected/found. |
| Part 2: Percentage of Participants With HDV RNA TND | Week 48, FU Week 24 | Percentage of participants with HDV RNA TND was reported. TND was defined as no traces of HBV RNA were detected/found. |
| Part 1: Percentage of Participants With Normal ALT | FU Week 24 | Percentage of participants with Normal ALT was reported. Normal ALT was defined as ALT \<ULN with ULN = 34 U/L for female and 43 U/L for male. |
| Part 2: Percentage of Participants With Normal ALT | FU Week 24 | Percentage of participants with Normal ALT was reported. Normal ALT was defined as ALT \<ULN with ULN = 34 U/L for female and 43 U/L for male. |
| Parts 1 and 2: Time to Reach HDV RNA >=2 log10 IU/mL Decline From Baseline or HDV RNA TND | Placebo + NA: From Day 1 up to Week 196; JNJ-3989 + NA: From Day 1 up to Week 192 | Time to reach HDV RNA \>=2 log10 IU/mL decline from baseline or HDV RNA TND was planned to be reported. It is defined as the number of days between the date of first study intervention intake and the date of the first occurrence of HDV RNA \>= 2 log10 IU/mL decline or HDV RNA TND, whichever event is first (that is, minute \[the date of the first HDV RNA \>= 2 log10 IU/mL decline, date of the first time HDV RNA is TND\] - the date of first study intervention intake + 1). TND was defined as no traces of HBV RNA were detected/found. The multiple imputation approach was derived using a longitudinal multiple regression model to impute missing data. |
| Part 1: Change From Baseline in HDV RNA | Baseline (Day 1), Week 48 | Change from baseline in HDV RNA was 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 intervention on Day 1. |
| Part 2: Change From Baseline in HDV RNA | Baseline (Day 1), Week 48 | Change from baseline in HDV RNA was 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 intervention on Day 1. |
| Part 1: Change From Baseline in ALT | Baseline (Day 1), Week 48, FU Week 24 | Change from baseline in ALT was 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 intervention on Day 1. |
| Part 2: Change From Baseline in ALT | Baseline (Day 1), Week 48, FU Week 44 | Change from baseline in ALT was 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 intervention on Day 1. |
| Parts 1 and 2: Percentage of Participants With Treatment-emergent Adverse Events (TEAEs) | Placebo + NA: DB Phase: Week 0 up to Week 52, OL Phase: Week 52 up to Week 148, FUP Phase: Week 148 up to Week 196; JNJ-3989 + NA: DB Phase: Week 0 up to Week 52, OL Phase: Week 52 up to Week 144; FUP Phase: Week 144 up to Week 192 | Percentage of participants with TEAEs was 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 study intervention. TEAE were all AEs with a start date on or after the first administration of study treatment or any ongoing event that worsens in severity, intensity or frequency after the first administration of study treatment. |
| Parts 1 and 2: Percentage of Participants With Treatment-emergent Serious Adverse Events (TESAEs) | Placebo + NA: DB Phase: Week 0 up to Week 52, OL Phase: Week 52 up to Week 148, FUP Phase: Week 148 up to Week 196; JNJ-3989 + NA: DB Phase: Week 0 up to Week 52, OL Phase: Week 52 up to Week 144; FUP Phase: Week 144 up to Week 192 | Percentage of participants with TESAEs was reported. 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. TESAE were all SAEs with a start date on or after the first administration of study treatment or any ongoing event that worsens in severity, intensity or frequency after the first administration of study treatment. |
| Parts 1 and 2: Percentage of Participants With Worst Treatment-emergent Abnormalities in Clinical Laboratory Tests: Chemistry | Placebo + NA: DB Phase: Week 0 up to Week 52, OL Phase: Week 52 up to Week 148, FUP Phase: Week 148 up to Week 196; JNJ-3989 + NA: DB Phase: Week 0 up to Week 52, OL Phase: Week 52 up to Week 144; FUP Phase: Week 144 up to Week 192 | Percentage of participants with worst treatment-emergent abnormalities in clinical laboratory tests: chemistry was reported. Laboratory abnormalities were graded according to the Division of Acquired Immunodeficiency Syndrome (DAIDS) criteria as follows: Grade 1 - Mild, Grade 2 - Moderate, Grade 3 - Severe, and Grade 4 - Potentially life threatening. Only Grade 3 and Grade 4 abnormalities were considered worst and are reported. Only those laboratory parameters for which at least one participant had an abnormality are reported in this outcome measure. ALT: Alanine Aminotransferase; AST: Aspartate Aminotransferase; SGPT: serum glutamic pyruvic transaminase; SGOT: serum glutamic-oxaloacetic transaminase. |
| Parts 1 and 2: Percentage of Participants With Worst Treatment-emergent Abnormalities in Clinical Laboratory Tests: Hematology | Placebo + NA: DB Phase: Week 0 up to Week 52; JNJ-3989 + NA: DB Phase: Week 0 up to Week 52 | Percentage of participants with worst treatment-emergent abnormalities in clinical laboratory tests: hematology was reported. Laboratory abnormalities were graded according to the DAIDS criteria as follows: Grade 1 - Mild, Grade 2 - Moderate, Grade 3 - Severe, and Grade 4 - Potentially life threatening. Only Grade 3 and Grade 4 abnormalities were considered worst and are reported. Only those laboratory parameters for which at least one participant had an abnormality are reported in this outcome measure. |
| Parts 1 and 2: Percentage of Participants With Worst Treatment-emergent Abnormalities in Clinical Laboratory Tests: Urinalysis | Placebo + NA: DB Phase: Week 0 up to Week 52, OL Phase: Week 52 up to Week 148, FUP Phase: Week 148 up to Week 196; JNJ-3989 + NA: DB Phase: Week 0 up to Week 52, OL Phase: Week 52 up to Week 144; FUP Phase: Week 144 up to Week 192 | Percentage of participants with worst treatment-emergent abnormalities in clinical laboratory tests: urinalysis was reported. Urinalysis included parameters: Glycosuria, Hematuria, and Proteinuria. Laboratory abnormalities were graded according to the DAIDS criteria as follows: Grade 1 - Mild, Grade 2 - Moderate, Grade 3 - Severe, and Grade 4 - Potentially life threatening. Only Grade 3 and Grade 4 abnormalities were considered worst and are reported. |
| Parts 1 and 2: Percentage of Participants With Worst Treatment-emergent Abnormalities in Clinical Laboratory Tests: Urine Chemistry | Placebo + NA: DB Phase: Week 0 up to Week 52, OL Phase: Week 52 up to Week 148, FUP Phase: Week 148 up to Week 196; JNJ-3989 + NA: DB Phase: Week 0 up to Week 52, OL Phase: Week 52 up to Week 144; FUP Phase: Week 144 up to Week 192 | Percentage of participants with worst treatment-emergent abnormalities in clinical laboratory tests: urine chemistry was reported. Laboratory abnormalities were graded according to the DAIDS criteria as follows: Grade 1 - Mild, Grade 2 - Moderate, Grade 3 - Severe, and Grade 4 - Potentially life threatening. Only Grade 3 and Grade 4 abnormalities were considered worst and are reported. |
| Parts 1 and 2: Percentage of Participants With Worst Treatment-emergent Abnormalities in Clinical Laboratory Tests: Renal Biomarkers | Placebo + NA: DB Phase: Week 0 up to Week 52, OL Phase: Week 52 up to Week 148, FUP Phase: Week 148 up to Week 196; JNJ-3989 + NA: DB Phase: Week 0 up to Week 52, OL Phase: Week 52 up to Week 144; FUP Phase: Week 144 up to Week 192 | Percentage of participants with worst treatment-emergent abnormalities in clinical laboratory tests: renal biomarkers was reported. Laboratory abnormalities were graded according to the DAIDS criteria as follows: Grade 1 - Mild, Grade 2 - Moderate, Grade 3 - Severe, and Grade 4 - Potentially life threatening. Only Grade 3 and Grade 4 abnormalities were considered worst and are reported. |
| Parts 1 and 2: Percentage of Participants With Worst Treatment-emergent Abnormalities in 12-Lead Electrocardiogram | Placebo + NA: DB Phase: Week 0 up to Week 52, OL Phase: Week 52 up to Week 148, FUP Phase: Week 148 up to Week 196; JNJ-3989 + NA: DB Phase: Week 0 up to Week 52, OL Phase: Week 52 up to Week 144; FUP Phase: Week 144 up to Week 192 | Percentage of participants with worst treatment-emergent abnormalities in 12-Lead Electrocardiogram was reported. Only those parameters were reported where at least one participant had abnormality. Worst ECG abnormalities were determined based on investigator's discretion. bpm: beats per minute; ms: milliseconds; QTcF: QT interval corrected for heart rate according to Fridericia; QTc: Corrected QT Interval. |
| Parts 1 and 2: Percentage of Participants With Worst Treatment-emergent Abnormalities in Vital Signs | Placebo + NA: DB Phase: Week 0 up to Week 52, OL Phase: Week 52 up to Week 148; JNJ-3989 + NA: DB Phase: Week 0 up to Week 52, OL Phase: Week 52 up to Week 144 | Percentage of participants with worst treatment-emergent abnormalities in vital signs (pulse rate, supine systolic blood pressure). Vital signs abnormalities were graded according to the DAIDS criteria as follows: Grade 1 - Mild, Grade 2 - Moderate, Grade 3 - Severe, and Grade 4 - Potentially life threatening. Only Grade 3 and Grade 4 abnormalities were considered worst and are reported. Only those laboratory parameters for which at least one participant had an abnormality are reported in this outcome measure. Only those parameters were reported where at least one participant had abnormality. Abn: abnormal |
| Parts 1 and 2: Percentage of Participants With Clinically Significant Abnormalities in Physical Examination | Placebo + NA: DB Phase: Week 0 up to Week 52, OL Phase: Week 52 up to Week 148, FUP Phase: Week 148 up to Week 196; JNJ-3989 + NA: DB Phase: Week 0 up to Week 52, OL Phase: Week 52 up to Week 144; FUP Phase: Week 144 up to Week 192 | Percentage of participants with clinically significant abnormalities in physical examination was reported. Vital signs abnormalities were graded according to the DAIDS criteria as follows: Grade 1 - Mild, Grade 2 - Moderate, Grade 3 - Severe, and Grade 4 - Potentially life threatening. |
| Parts 1 and 2: Percentage of Participants With Hepatitis B Surface Antigen (HBsAg) Seroclearance | Week 48, FU Week 24 | Percentage of participants with HBsAg seroclearance was reported. HBsAg seroclearance is defined as the quantitative HBsAg \< LLOQ. |
| Part 1: Change From Baseline Over Time in HBsAg | Baseline (Day 1), Week 48, FU Week 24 | Change from baseline over time in HBsAg was 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 intervention on Day 1. |
| Part 2: Change From Baseline Over Time in HBsAg | Baseline (Day 1), Week 48, FU Week 24 | Change from baseline over time in HBsAg was 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 intervention on Day 1. |
| Part 1: Change From Baseline Over Time in Hepatitis B Virus e Antigen (HBeAg) | Baseline (Day 1), Week 48, FU Week 24 | Change from baseline over time in HBeAg was 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 intervention on Day 1. |
| Part 2: Change From Baseline Over Time in HBeAg | Baseline (Day 1), Week 48, FU Week 24 | Change from baseline over time in HBeAg was 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 intervention on Day 1. |
| Part 1: Change From Baseline Over Time in Hepatitis B Virus (HBV) Deoxyribonucleic Acid (DNA) | Baseline (Day 1), Weeks 48 , 136, EOS (FU Week 48) | Change from baseline over time in HBV DNA was 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 intervention on Day 1. |
| Part 2: Change From Baseline Over Time in HBV DNA | Baseline (Day 1), Weeks 48, 112, EOS (FU Week 48) | Change from baseline over time in HBV DNA was 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 intervention on Day 1. |
| Part 1: Percentage of Participants With HBsAg Levels Below/Above Different Cut-offs | Week 48, FU Week 24 | Percentage of participants with HBsAg levels below/above different cut-offs was reported. HBsAg values (IU/mL) were \<1,000, \<100, \<10, \<1, and \<0.05 IU/mL (i.e, \<LLOQ). LLOQ value is 0.05 IU/mL. |
| Part 2: Percentage of Participants With HBsAg Levels Below/Above Different Cut-offs | Week 48, FU Week 24 | Percentage of participants with HBsAg levels below/above different cut-offs was reported. HBsAg values (IU/mL) were \<1,000, \<100, \<10, \<1, and \<0.05 IU/mL (i.e, \<LLOQ). LLOQ value is 0.05 IU/mL. |
| Part 1: Percentage of Participants With HBeAg Levels Below/Above Different Cut-offs | Week 48, FU Week 24 | Percentage of participants with HBeAg levels below/above different cut-offs was reported. Cut-offs were \>= 0.5 log10 IU/mL, \>= 1.0 log10 IU/mL, \>= 2.0 log10 IU/mL, and \>= 3.0 log10 IU/mL. |
| Part 2: Percentage of Participants With HBeAg Levels Below/Above Different Cut-offs | Week 48, FU Week 24 | Percentage of participants with HBeAg levels below/above different cut-offs was reported. Cut-offs were \>= 0.5 log10 IU/mL, \>= 1.0 log10 IU/mL, \>= 2.0 log10 IU/mL, and \>= 3.0 log10 IU/mL. |
| Part 1: Percentage of Participants With HBV DNA Levels Below/Above Different Cut-offs | Week 48, FU Week 24 | Percentage of participants with HBV DNA levels below/above different cut-offs (\<LLOQ and \<2000 IU/mL) was reported. For HBV DNA, LLOQ is 20 IU/mL. |
| Part 2: Percentage of Participants With HBV DNA Levels Below/Above Different Cut-offs | Week 48, FU Week 24 | Percentage of participants with HBV DNA levels below/above different cut-offs (\<LLOQ and \<2000 IU/mL). For HBV DNA, LLOQ is 20 IU/mL |
| Part 1: Time to Reach HBsAg <1 IU/mL Based on Kaplan-Meier Estimate | Placebo + NA: From baseline up to Week 196; JNJ-3989 + NA: From baseline up to Week 192 | Time to reach HBsAg \<1 IU/mL based on Kaplan-Meier estimate was reported. Time to first occurrence of the HBsAg \<1 IU/mL is defined as the number of days between the date of first study intervention intake and the date of the first occurrence of the HBsAg \<1 IU/mL. 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 intervention on Day 1. |
| Part 2: Time to Reach HBsAg <1 IU/mL Based on Kaplan-Meier Estimate | Placebo + NA: From baseline up to Week 196; JNJ-3989 + NA: From baseline up to Week 192 | Time to reach HBsAg \<1 IU/mL based on Kaplan-Meier estimate was reported. Time to first occurrence of the HBsAg \<1 IU/mL is defined as the number of days between the date of first study intervention intake and the date of the first occurrence of the HBsAg \<1 IU/mL. 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 intervention on Day 1. |
| Part 1: Percentage of Participants With HBV DNA Virologic Breakthrough | Week 48, FU Week 24 | Percentage of participants with HBV DNA virologic breakthrough was reported. Virologic Breakthrough was defined as confirmed on-treatment 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 \<LLOQ of the HBV DNA assay. |
| Part 2: Percentage of Participants With HBV DNA Virologic Breakthrough | Week 48, FU Week 24 | Percentage of participants with HBV DNA virologic breakthrough was reported. Virologic Breakthrough was defined as confirmed on-treatment 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 \<LLOQ of the HBV DNA assay. |
| Parts 1 and 2: Maximum Plasma Concentration (Cmax) of JNJ-3976 | Weeks 4, 8, and 16 | Maximum plasma concentration (Cmax) of JNJ-3976 were reported. Participant wise data is reported as n\<3. |
| Parts 1 and 2: Maximum Plasma Concentration (Cmax) of JNJ-3924 | Weeks 4, 8, and 16 | Maximum plasma concentration (Cmax) of JNJ-3924 was reported. Participant wise data is reported as n\<3. |
| Parts 1 and 2: Area Under the Plasma Concentration-time Curve From Time 0 to 24 Hours (AUC[0-24h]) of JNJ-3976 | Predose up to 24 hours post dose on Weeks 4, 8, and 16 | Area under the plasma concentration-time curve from time 0 to 24 hours (AUC\[0-24h\]) of JNJ-3976 were reported. Participant wise data is reported as n\<3. |
| Parts 1 and 2: Area Under the Plasma Concentration-time Curve From Time 0 to 24 Hours (AUC[0-24h]) of JNJ-3924 | Predose up to 24 hours post dose on Weeks 4, 8, and 16 | Area under the plasma concentration-time curve from time 0 to 24 hours (AUC\[0-24h\]) of JNJ-3924 were reported. Participant wise data is reported as n\<3. |
| Parts 1 and 2: Area Under the Plasma Concentration-time Curve From Time 0 to Last Quantifiable Time (AUC[0-last]) of JNJ-3976 | Weeks 4, 8, and 16 | Area under the plasma concentration-time curve from time 0 to Last Quantifiable Time (AUC\[0-last\]) of JNJ-3976 were reported. Participant wise data is reported as n\<3. |
| Parts 1 and 2: Area Under the Plasma Concentration-time Curve From Time 0 to Last Quantifiable Time (AUC[0-last]) of JNJ-3924 | Weeks 4, 8, and 16 | Area under the plasma concentration-time curve from time 0 to Last Quantifiable Time (AUC\[0-last\]) of JNJ-3924 were reported. Participant wise data is reported as n\<3. |
| Part 1: Percentage of Participants With >=2 Kilopascals (kPa) Reduction From Baseline in Liver Stiffness Measurement (LSM) Assessed by Vibration-controlled Transient Elastography (VCTE; FibroScan) | Baseline, EOS (FU Week 48) | Percentage of participants with \>=2 kPa reduction from baseline \>=2 kPa in liver stiffness measurement (LSM) assessed by VCTE (fibroScan) was 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 intervention on Day 1. |
| Part 2: Percentage of Participants With >=2 kPa Reduction From Baseline in Liver Stiffness Measurement (LSM) Assessed by VCTE (FibroScan) | Baseline, EOS (FU Week 48) | Percentage of participants with \>=2 kPa reduction from baseline in liver stiffness measurement (LSM) assessed by VCTE (FibroScan) was 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 intervention on Day 1. |
| Part 1: Change From Baseline in LSM Over Time Assessed by VCTE (FibroScan) | Baseline, Week 48, FU Week 24 | Change from baseline in LSM over time assessed by VCTE (FibroScan) was 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 intervention on Day 1. |
| Part 2: Change From Baseline in LSM Over Time Assessed by VCTE (FibroScan) | Baseline, Week 48, FU Week 24 | Change from baseline in LSM over time assessed by VCTE (FibroScan) was 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 intervention on Day 1. |
| Part 1: Percentage of Participants With Sustained HDV Response Off-treatment Post End of JNJ-3989 Treatment | JNJ-73763989 (JNJ-3989) + Nucleos(t)Ide Analog (NA): Post end of treatment (Week 144) up to FU Week 48; Placebo + NA: Post end of treatment (Week 148) up to FU Week 48 | Percentage of participants with sustained HDV response Off-treatment post end of JNJ-3989 treatment was reported. A JNJ-3989 off-treatment sustained HDV response is defined by having HDV RNA TND during the FU phase after stopping JNJ-3989 regardless of continuing NA treatment. |
| Part 2: Percentage of Participants With Sustained HDV Response Off-treatment Post End of JNJ-3989 Treatment | JNJ-73763989 (JNJ-3989) + Nucleos(t)Ide Analog (NA): Post end of treatment (Week 144) up to FU Week 48; Placebo + NA: Post end of treatment (Week 148) up to FU Week 48 | Percentage of participants with sustained HDV response Off-treatment post end of JNJ-3989 treatment was reported. A JNJ-3989 off-treatment sustained HDV response is defined by having HDV RNA TND during the FU phase after stopping JNJ-3989 regardless of continuing NA treatment. |
| Part 1: Percentage of Participants With HDV Relapse Post End of JNJ-3989 Treatment | JNJ-73763989 (JNJ-3989) + Nucleos(t)Ide Analog (NA): Post end of treatment (Week 144) up to FU Week 48; Placebo + NA: Post end of treatment (Week 148) up to FU Week 48 | Percentage of participants with HDV relapse post end of JNJ-3989 treatment was reported. Off-treatment HDV relapse is defined as: 1. In participants with HDV RNA \<LLOQ (i.e., 630 IU/ml) at EOT: Confirmed increase in HDV RNA of \> 1 log10 IU/mL above the LLOQ JNJ-3989 off-treatment. 2. In participants with HDV RNA \>LLOQ at EOT: Confirmed increase in HDV RNA of \> 1 log10 IU/mL from EOT HDV RNA value JNJ-3989 off-treatment. |
| Part 2: Percentage of Participants With HDV Relapse Post End of JNJ-3989 Treatment | JNJ-73763989 (JNJ-3989) + Nucleos(t)Ide Analog (NA): Post end of treatment (Week 144) up to FU Week 48; Placebo + NA: Post end of treatment (Week 148) up to FU Week 48 | Percentage of participants with HDV relapse post end of JNJ-3989 treatment was reported. Off-treatment HDV relapse is defined as: 1. In participants with HDV RNA \<LLOQ (i.e., 630 IU/ml) at EOT: Confirmed increase in HDV RNA of \> 1 log10 IU/mL above the LLOQ JNJ-3989 off-treatment. 2. In participants with HDV RNA \>LLOQ at EOT: Confirmed increase in HDV RNA of \> 1 log10 IU/mL from EOT HDV RNA value JNJ-3989 off-treatment. |
| Parts 1 and 2: Percentage of Participants With Sustained HBV Response Off-treatment Post End of JNJ-3989 Treatment | JNJ-73763989 (JNJ-3989) + Nucleos(t)Ide Analog (NA): Post end of treatment (Week 144) up to FU Week 48; Placebo + NA: Post end of treatment (Week 148) up to FU Week 48 | Percentage of participants with sustained HBV response off-treatment post end of JNJ-3989 treatment was reported. |
| Part 1: Percentage of Participants With HBV Flare (Virologic, Biochemical, and Clinical) Post End of Treatment | JNJ-73763989 (JNJ-3989) + Nucleos(t)Ide Analog (NA): Post end of treatment (Week 144) up to FU Week 48; Placebo + NA: Post end of treatment (Week 148) up to FU Week 48 | Percentage of participants with HBV flare (Virologic, biochemical, and clinical) post end of treatment was reported. Off-treatment is defined as the time period as the periods when the participants do not receive any of the study interventions (JNJ-3989/placebo and NA). Virologic flare is for participants who are off-treatment and had HBV DNA \< LLOQ at the last observed point on all study treatments, and categorized based on the confirmed (i.e., two consecutive values) peak HBV DNA above any of the three thresholds: 20000 IU/mL, 2000 IU/mL and 200 IU/mL. Biochemical HBV flare is defined as a confirmed ALT and/or AST\>=3\*ULN and \>=3\* nadir (i.e. lowest value observed up to the time point of meeting the biochemical flare criteria). An HBV clinical flare occurs either when an HBV virologic flare and off-treatment HBV biochemical flare overlap in time or when a HBV biochemical flare starts within 4 weeks following the end of an HBV virologic flare. |
| Part 2: Percentage of Participants With HBV Flare (Virologic, Biochemical, and Clinical) Post End of Treatment | JNJ-73763989 (JNJ-3989) + Nucleos(t)Ide Analog (NA): Post end of treatment (Week 144) up to FU Week 48; Placebo + NA: Post end of treatment (Week 148) up to FU Week 48 | Percentage of participants with HBV flare (Virologic, biochemical, and clinical) post end of treatment was reported was reported. Off-treatment is defined as the time period as the periods when the participants do not receive any of the study interventions (JNJ-3989/placebo and NA). Virologic flare (Derivation 1) is for participants who are off-treatment and had HBV DNA \< LLOQ at the last observed point on all study treatments, and categorized based on the confirmed (i.e., two consecutive values) peak HBV DNA above any of the three thresholds: 20000 IU/mL, 2000 IU/mL and 200 IU/mL. Biochemical HBV flare is defined as a confirmed ALT and/or AST\>=3\*ULN and \>=3\* nadir (i.e. lowest value observed up to the time point of meeting the biochemical flare criteria). An HBV clinical flare occurs either when an HBV virologic flare and off-treatment HBV biochemical flare overlap in time or when a HBV biochemical flare starts within 4 weeks following the end of an HBV virologic flare. |
Countries
Australia, Brazil, China, France, Germany, Italy, Japan, New Zealand, Russia, Spain, Sweden, Taiwan, Turkey (Türkiye), United Kingdom, United States
Contacts
STUDY_DIRECTORJanssen Research & Development, LLC Clinical Trial
Janssen Research & Development, LLC
Participant flow
Recruitment details
Adult participants co-infected with hepatitis B virus (HBV) and hepatitis D virus (HDV) were considered eligible for participation. Participants with compensated cirrhosis were allowed to be enrolled in Part 1 but excluded from Part 2 of the study.
Pre-assignment details
The study consisted of 2 parts: 1 and 2. Part 2 was initiated when the protocol specified antiviral activity criteria was met in Part 1 and when all participants of Part 1 had completed at least Week 16 or discontinued earlier. Unique participants were randomized (4:1) to JNJ-73763989 + NA and Placebo + NA in Part 1 and 2.
Participants by arm
| Arm | Count |
|---|---|
| Part 1: JNJ-73763989 + Nucleos(t)Ide Analog (NA) In the double-blind phase, participants received JNJ-73763989 100 milligrams (mg) subcutaneous (SC) injection every 4 weeks (Q4W) along with NA (entecavir \[ETV\] monohydrate 0.5 mg, tenofovir disoproxil 245 mg, or tenofovir alafenamide \[TAF\] 25 mg) tablet orally once daily for 52 weeks. After completion of double-blind phase, participants entered open-label phase and continued to receive JNJ-73763989 100 mg SC injection Q4W along with NA (ETV 0.5 mg, tenofovir disoproxil 245 mg, or TAF 25 mg) tablet orally once daily for 92 weeks (up to Week 144). After completion of open-label phase, participants entered 48-week follow-up phase during which JNJ-73633989 treatment was stopped and NA treatment alone was continued. | 17 |
| Part 1: Placebo + NA In the double-blind phase, participants received placebo matching to JNJ-73763989 SC injection Q4W along with NA (ETV 0.5 mg, tenofovir disoproxil 245 mg, or TAF 25 mg) tablet orally once daily for 52 weeks. After completion of double-blind phase, participants entered open-label phase and received JNJ-73763989 100 mg SC injection Q4W along with NA (ETV 0.5 mg, tenofovir disoproxil 245 mg, or TAF 25 mg) tablet orally once daily for 96 weeks (up to Week 148). After completion of open-label phase, participants entered 48-week follow-up phase during which JNJ-73633989 treatment was stopped and NA treatment alone was continued. | 5 |
| Part 2: JNJ-73763989 + NA In the double-blind phase, participants received JNJ-73763989 100 mg SC injection Q4W along with NA (ETV 0.5 mg, tenofovir disoproxil 245 mg, or TAF 25 mg) tablet orally once daily for 52 weeks. After completion of double-blind phase, participants entered open-label phase and continued to receive JNJ-73763989 100 mg SC injection Q4W along with NA (ETV 0.5 mg, tenofovir disoproxil 245 mg, or TAF 25 mg) tablet orally once daily for 92 weeks (up to Week 144). After completion of open-label phase, participants entered 48-week follow-up phase and stopped JNJ-73633989 treatment and continued NA treatment alone. | 24 |
| Part 2: Placebo + NA In the double-blind phase, participants received placebo matching to JNJ-73763989 SC injection Q4W along with NA (ETV 0.5 mg, tenofovir disoproxil 245 mg, or TAF 25 mg) tablet orally once daily for 52 weeks. After completion of double-blind phase, participants entered open-label phase and received JNJ-73763989 100 mg SC injection Q4W along with NA (ETV 0.5 mg, tenofovir disoproxil 245 mg, or TAF 25 mg) tablet orally once daily for 96 weeks (up to Week 148). After completion of open-label phase, participants entered 48-week follow-up phase and stopped JNJ-73633989 treatment and continued NA treatment alone. | 6 |
| Total | 52 |
Baseline characteristics
| Characteristic | Part 1: JNJ-73763989 + Nucleos(t)Ide Analog (NA) | Total | Part 2: Placebo + NA | Part 2: JNJ-73763989 + NA | Part 1: Placebo + NA |
|---|---|---|---|---|---|
| Age, Continuous | 40.9 years STANDARD_DEVIATION 10.44 | 43 years STANDARD_DEVIATION 10.11 | 44.8 years STANDARD_DEVIATION 11.96 | 43.8 years STANDARD_DEVIATION 9.49 | 44.2 years STANDARD_DEVIATION 11.88 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 15 Participants | 50 Participants | 6 Participants | 24 Participants | 5 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 3 Participants | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 4 Participants | 1 Participants | 2 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 2 Participants | 4 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 13 Participants | 41 Participants | 4 Participants | 20 Participants | 4 Participants |
| Region of Enrollment France | 0 Participants | 2 Participants | 0 Participants | 2 Participants | 0 Participants |
| Region of Enrollment Germany | 0 Participants | 2 Participants | 1 Participants | 1 Participants | 0 Participants |
| Region of Enrollment Italy | 0 Participants | 10 Participants | 2 Participants | 8 Participants | 0 Participants |
| Region of Enrollment New Zealand | 4 Participants | 6 Participants | 0 Participants | 1 Participants | 1 Participants |
| Region of Enrollment Russian Federation | 3 Participants | 3 Participants | 0 Participants | 0 Participants | 0 Participants |
| Region of Enrollment Spain | 3 Participants | 4 Participants | 0 Participants | 1 Participants | 0 Participants |
| Region of Enrollment Sweden | 1 Participants | 2 Participants | 0 Participants | 1 Participants | 0 Participants |
| Region of Enrollment Taiwan | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants |
| Region of Enrollment Turkey | 2 Participants | 15 Participants | 1 Participants | 8 Participants | 4 Participants |
| Region of Enrollment United Kingdom | 3 Participants | 5 Participants | 1 Participants | 1 Participants | 0 Participants |
| Region of Enrollment United States | 1 Participants | 2 Participants | 0 Participants | 1 Participants | 0 Participants |
| Sex: Female, Male Female | 8 Participants | 23 Participants | 3 Participants | 9 Participants | 3 Participants |
| Sex: Female, Male Male | 9 Participants | 29 Participants | 3 Participants | 15 Participants | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk | EG010 affected / at risk | EG011 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 17 | 0 / 5 | 0 / 24 | 0 / 6 | 0 / 5 | 0 / 4 | 0 / 14 | 0 / 5 | 0 / 14 | 0 / 4 | 0 / 19 | 0 / 5 |
| other Total, other adverse events | 17 / 17 | 3 / 5 | 17 / 24 | 5 / 6 | 4 / 5 | 4 / 4 | 8 / 14 | 3 / 5 | 11 / 14 | 3 / 4 | 7 / 19 | 2 / 5 |
| serious Total, serious adverse events | 2 / 17 | 0 / 5 | 3 / 24 | 0 / 6 | 0 / 5 | 1 / 4 | 0 / 14 | 0 / 5 | 1 / 14 | 0 / 4 | 0 / 19 | 0 / 5 |
Outcome results
Primary
Double-blind: Part 1: Percentage of Participants With HDV Ribonucleic Acid (RNA) >=2 log10 IU/mL Decline From Baseline or HDV RNA Target Not Detected (TND) in Combination With Normal Alanine Aminotransferase (ALT) at Week 48 (Multiple Imputation Approach)
Percentage of participants with HDV RNA greater than or equal to (\>=) 2 log10 International Units Per Milliliter (IU/mL) decline from baseline or HDV RNA TND in combination with normal ALT at Week 48 using multiple imputation approach was reported. Target not detected (TND) was defined as no traces of HBV RNA were detected/found. Normal ALT was defined as ALT less than (\<) upper limit of normal (ULN) with ULN = 34 units per liter (U/L) for female and 43 U/L for male. 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 intervention on Day 1. The multiple imputation approach was derived using a longitudinal multiple regression model to impute missing data.
Time frame: At Week 48
Population: Intent-to-Treat analysis set (ITT) included all participants who were randomly assigned to an intervention arm and who received at least 1 dose of study intervention. Participants were analyzed according to the study intervention they were randomly assigned to.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part 1: JNJ-73763989 + Nucleos(t)Ide Analog (NA) | Double-blind: Part 1: Percentage of Participants With HDV Ribonucleic Acid (RNA) >=2 log10 IU/mL Decline From Baseline or HDV RNA Target Not Detected (TND) in Combination With Normal Alanine Aminotransferase (ALT) at Week 48 (Multiple Imputation Approach) | 23.5 Percentage of Participants |
| Part 1: Placebo + NA | Double-blind: Part 1: Percentage of Participants With HDV Ribonucleic Acid (RNA) >=2 log10 IU/mL Decline From Baseline or HDV RNA Target Not Detected (TND) in Combination With Normal Alanine Aminotransferase (ALT) at Week 48 (Multiple Imputation Approach) | 0.0 Percentage of Participants |
Comparison: Stratum-adjusted Mantel-Haenszel (MH) test was used to assess the difference of percentage based on stratification factor: HBeAg status at screening (positive vs negative).p-value: 0.01195% CI: [3.52, 43.96]Mantel-Haenszel
Primary
Double-blind: Part 2: Percentage of Participants With HDV RNA >=2 log10 IU/mL Decline From Baseline or HDV RNA TND in Combination With ALT at Week 48 (Multiple Imputation Approach)
Percentage of participants with HDV RNA \>=2 log10 IU/mL decline from baseline or HDV RNA TND in combination with normal ALT at Week 48 using multiple imputation approach was reported. TND was defined as no traces of HBV RNA were detected/found. Normal ALT was defined as ALT \<ULN with ULN = 34 U/L for female and 43 U/L for male. 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 intervention on Day 1. The multiple imputation approach was derived using a longitudinal multiple regression model to impute missing data.
Time frame: At Week 48
Population: ITT analysis set included all participants who were randomly assigned to an intervention arm and who received at least 1 dose of study intervention. Participants were analyzed according to the study intervention they were randomly assigned to.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part 1: JNJ-73763989 + Nucleos(t)Ide Analog (NA) | Double-blind: Part 2: Percentage of Participants With HDV RNA >=2 log10 IU/mL Decline From Baseline or HDV RNA TND in Combination With ALT at Week 48 (Multiple Imputation Approach) | 27.1 Percentage of Participants |
| Part 1: Placebo + NA | Double-blind: Part 2: Percentage of Participants With HDV RNA >=2 log10 IU/mL Decline From Baseline or HDV RNA TND in Combination With ALT at Week 48 (Multiple Imputation Approach) | 0.0 Percentage of Participants |
Comparison: Stratum-adjusted MH test was used to assess the difference of percentage based on stratification factor: HBeAg status at screening (positive vs negative).p-value: 0.00395% CI: [7.38, 46.21]Mantel-Haenszel