Trial Outcomes & Findings for A Study of JNJ-73763989, Pegylated Interferon Alpha-2a and Nucleos(t)Ide Analogs in Participants With Chronic Hepatitis B Virus Infection (NCT NCT05005507)

Results Overview

Percentage of participants with a reduction of at least 2log10 IU/mL in HBsAg levels from baseline at Week 24 (EOSI) were planned to be reported.

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

1 participants

Primary outcome timeframe

Week 24

Results posted on

2024-03-06

Participant Flow

Only 1 participant was enrolled in the study in Arm 1: JNJ-73763989 + nucleos(t)ide analog (NA) + pegylated interferon alpha-2a (PegIFN-alpha-2a) but did not complete the study. Participants were also planned to be enrolled in Arms 2 and 3 but were not enrolled as the study terminated prematurely based on a strategic decision and not for safety reasons.

Participant milestones

Participant milestones
Measure	Arm 1: JNJ-73763989+Nucleos(t)Ide Analog (NA)+PegIFN-alpha-2a Participants received JNJ-73763989 200 milligrams (mg) subcutaneous (SC) injection on Day 1 plus NA treatment (entecavir \[ETV\] 0.5 mg tablet) orally once daily from Day 1 to Day 16 plus pegylated interferon alpha-2a (PegIFN-alpha-2a) 180 micrograms (mcg) SC injection on Days 1, 8, and 15.
Overall Study STARTED	1
Overall Study COMPLETED	0
Overall Study NOT COMPLETED	1

Reasons for withdrawal

Reasons for withdrawal
Measure	Arm 1: JNJ-73763989+Nucleos(t)Ide Analog (NA)+PegIFN-alpha-2a Participants received JNJ-73763989 200 milligrams (mg) subcutaneous (SC) injection on Day 1 plus NA treatment (entecavir \[ETV\] 0.5 mg tablet) orally once daily from Day 1 to Day 16 plus pegylated interferon alpha-2a (PegIFN-alpha-2a) 180 micrograms (mcg) SC injection on Days 1, 8, and 15.
Overall Study Premature termination of study	1

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Arm 1: JNJ-73763989+Nucleos(t)Ide Analog (NA)+PegIFN-alpha-2a n=1 Participants Participants received JNJ-73763989 200 milligrams (mg) subcutaneous (SC) injection on Day 1 plus NA treatment (entecavir \[ETV\] 0.5 mg tablet) orally once daily from Day 1 to Day 16 plus pegylated interferon alpha-2a (PegIFN-alpha-2a) 180 micrograms (mcg) SC injection on Days 1, 8, and 15.
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	1 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants
Age, Continuous	46 years STANDARD_DEVIATION NA • n=5 Participants
Sex: Female, Male Female	0 Participants n=5 Participants
Sex: Female, Male Male	1 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	1 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants
Race (NIH/OMB) White	1 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants

PRIMARY outcome

Timeframe: Week 24

Population: Full analysis set (FAS) included all participants who were randomly assigned to an intervention arm in the intervention-specific appendix (ISA) and received at least 1 dose of study intervention. The data was not collected and analyzed for this outcome measure due to premature termination of the study.

Percentage of participants with a reduction of at least 2log10 IU/mL in HBsAg levels from baseline at Week 24 (EOSI) were planned to be reported.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Up to 1 month 26 days

Population: Safety analysis set included all participants who received at least 1 dose of study intervention within the ISA.

An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship.

Outcome measures

Outcome measures
Measure	Arm 1: JNJ-73763989+Nucleos(t)Ide Analog (NA)+PegIFN-alpha-2a n=1 Participants Participants received JNJ-73763989 200 milligrams (mg) subcutaneous (SC) injection on Day 1 plus NA treatment (entecavir \[ETV\] 0.5 mg tablet) orally once daily from Day 1 to Day 16 plus pegylated interferon alpha-2a (PegIFN-alpha-2a) 180 micrograms (mcg) SC injection on Days 1, 8, and 15.
Percentage of Participants With Adverse Events (AEs)	0 Percentage of participants

SECONDARY outcome

Timeframe: Up to 1 month 26 days

Population: Safety analysis set included all participants who received at least 1 dose of study intervention within the ISA.

An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. SAE is any untoward medical occurrence that at any dose may result in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, is a suspected transmission of any infectious agent via a medicinal product.

Outcome measures

Outcome measures
Measure	Arm 1: JNJ-73763989+Nucleos(t)Ide Analog (NA)+PegIFN-alpha-2a n=1 Participants Participants received JNJ-73763989 200 milligrams (mg) subcutaneous (SC) injection on Day 1 plus NA treatment (entecavir \[ETV\] 0.5 mg tablet) orally once daily from Day 1 to Day 16 plus pegylated interferon alpha-2a (PegIFN-alpha-2a) 180 micrograms (mcg) SC injection on Days 1, 8, and 15.
Percentage of Participants With Serious Adverse Events (SAEs)	0 Percentage of participants

SECONDARY outcome

Timeframe: Up to 1 month 26 days

Population: Safety analysis set included all participants who received at least 1 dose of study intervention within the ISA.

Percentage of participants with abnormalities in clinical laboratory tests including hematology, blood coagulation, blood biochemistry, urinalysis, urine chemistry, renal biomarkers, were reported.

Outcome measures

Outcome measures
Measure	Arm 1: JNJ-73763989+Nucleos(t)Ide Analog (NA)+PegIFN-alpha-2a n=1 Participants Participants received JNJ-73763989 200 milligrams (mg) subcutaneous (SC) injection on Day 1 plus NA treatment (entecavir \[ETV\] 0.5 mg tablet) orally once daily from Day 1 to Day 16 plus pegylated interferon alpha-2a (PegIFN-alpha-2a) 180 micrograms (mcg) SC injection on Days 1, 8, and 15.
Percentage of Participants With Abnormalities in Clinical Laboratory Tests Hematology	0 Percentage of participants
Percentage of Participants With Abnormalities in Clinical Laboratory Tests Blood coagulation	0 Percentage of participants
Percentage of Participants With Abnormalities in Clinical Laboratory Tests Blood biochemistry	0 Percentage of participants
Percentage of Participants With Abnormalities in Clinical Laboratory Tests Urinalysis	0 Percentage of participants
Percentage of Participants With Abnormalities in Clinical Laboratory Tests Urine chemistry	0 Percentage of participants
Percentage of Participants With Abnormalities in Clinical Laboratory Tests Renal biomarker	0 Percentage of participants

SECONDARY outcome

Timeframe: Up to 1 month 26 days

Population: Safety analysis set included all participants who received at least 1 dose of study intervention within the ISA.

Percentage of participants with abnormalities in 12-Lead ECGs were reported.

Outcome measures

Outcome measures
Measure	Arm 1: JNJ-73763989+Nucleos(t)Ide Analog (NA)+PegIFN-alpha-2a n=1 Participants Participants received JNJ-73763989 200 milligrams (mg) subcutaneous (SC) injection on Day 1 plus NA treatment (entecavir \[ETV\] 0.5 mg tablet) orally once daily from Day 1 to Day 16 plus pegylated interferon alpha-2a (PegIFN-alpha-2a) 180 micrograms (mcg) SC injection on Days 1, 8, and 15.
Percentage of Participants With Abnormalities in 12-Lead Electrocardiograms (ECGs)	0 Percentage of participants

SECONDARY outcome

Timeframe: Up to 1 month 26 days

Population: Safety analysis set included all participants who received at least 1 dose of study intervention within the ISA.

Percentage of participants with abnormalities in vital signs were reported.

Outcome measures

Outcome measures
Measure	Arm 1: JNJ-73763989+Nucleos(t)Ide Analog (NA)+PegIFN-alpha-2a n=1 Participants Participants received JNJ-73763989 200 milligrams (mg) subcutaneous (SC) injection on Day 1 plus NA treatment (entecavir \[ETV\] 0.5 mg tablet) orally once daily from Day 1 to Day 16 plus pegylated interferon alpha-2a (PegIFN-alpha-2a) 180 micrograms (mcg) SC injection on Days 1, 8, and 15.
Percentage of Participants With Abnormalities in Vital Signs	0 Percentage of participants

SECONDARY outcome

Timeframe: Weeks 8 and 20

Population: Safety analysis set included all participants who received at least 1 dose of study intervention within the ISA. The data was not collected and analyzed for this outcome measure due to premature termination of the study.

Percentage of participants with abnormalities in ophthalmologic examination were planned to be reported.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Week 24

Population: Safety analysis set included all participants who received at least 1 dose of study intervention within the ISA. The data was not collected and analyzed for this outcome measure due to premature termination of the study.

Percentage of participants with abnormalities in physical examination were planned to be reported.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Week 24 (EOSI) and follow-up Week 2

Population: FAS included all participants who were randomly assigned to an intervention arm in the ISA and received at least 1 dose of study intervention. The data was not collected and analyzed for this outcome measure due to premature termination of the study.

Percentage of participants meeting the protocol-defined NA treatment completion criteria based on the Week 24 (EOSI) or follow-up Week 2 visits was planned to be reported. NA treatment completion criteria were as follows: (a) participant had alanine transaminase (ALT) \<3\*upper limits of normal (ULN); (b) participant had Hepatitis B Virus (HBV) Deoxyribonucleic acid (DNA) \<20 international units per milliliter (IU/mL); (c) participant was Hepatitis B e antigen (HBeAg)-negative; (d) participant had Hepatitis B surface antigen (HBsAg\<10 IU/mL.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Follow-up Weeks 24 and 48

Population: FAS included all participants who were randomly assigned to an intervention arm in the ISA and received at least 1 dose of study intervention. The data was not collected and analyzed for this outcome measure due to premature termination of the study.

Percentage of participants with HBsAg seroclearance at follow-up Weeks 24 and 48 without re-starting NA treatment were planned to be reported. Seroclearance of HBsAg is defined as a (quantitative) HBsAg level \<lower limit of quantitation (LLOQ). LLOQ is 0.05 International Units per milliliter (IU/mL).

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Follow-up Weeks 24 and 48

Population: FAS included all participants who were randomly assigned to an intervention arm in the ISA and received at least 1 dose of study intervention. The data was not collected and analyzed for this outcome measure due to premature termination of the study.

Percentage of participants with HBV DNA \<LLOQ at follow-up Weeks 24 and 48 without re-starting NA treatment were planned to be reported. LLOQ is 0.05 IU/mL.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Up to 1 month 26 days

Population: FAS included all participants who were randomly assigned to an intervention arm in the ISA and received at least 1 dose of study intervention.

Percentage of participants with virologic flares were reported. The start of a confirmed virologic flare is defined as the first date of two consecutive visits with HBV DNA \>200 IU/mL. The end date of the same confirmed virologic flare is defined as the first date when HBV DNA value returns to less than or equal to (\<=)200 IU/mL or the date of NA treatment restart, whichever comes first.

Outcome measures

Outcome measures
Measure	Arm 1: JNJ-73763989+Nucleos(t)Ide Analog (NA)+PegIFN-alpha-2a n=1 Participants Participants received JNJ-73763989 200 milligrams (mg) subcutaneous (SC) injection on Day 1 plus NA treatment (entecavir \[ETV\] 0.5 mg tablet) orally once daily from Day 1 to Day 16 plus pegylated interferon alpha-2a (PegIFN-alpha-2a) 180 micrograms (mcg) SC injection on Days 1, 8, and 15.
Percentage of Participants With Virologic Flares	0 Percentage of participants

SECONDARY outcome

Timeframe: Up to 1 month 26 days

Population: FAS included all participants who were randomly assigned to an intervention arm in the ISA and received at least 1 dose of study intervention.

Percentage of participants with biochemical flares were reported. The start date of a confirmed off-treatment biochemical flare: the first date of two consecutive visits with ALT and/or AST\>=3x ULN and \>=3x off-treatment/on-treatment nadir (that is, lowest value observed during off-treatment period up to the time point of meeting the biochemical flare criteria) while the participant does not receive any of the study interventions. The end date of the same off-treatment/on-treatment biochemical flare: the first date when there is a 50% reduction from the peak ALT and/or AST level \& \<3x ULN.

Outcome measures

Outcome measures
Measure	Arm 1: JNJ-73763989+Nucleos(t)Ide Analog (NA)+PegIFN-alpha-2a n=1 Participants Participants received JNJ-73763989 200 milligrams (mg) subcutaneous (SC) injection on Day 1 plus NA treatment (entecavir \[ETV\] 0.5 mg tablet) orally once daily from Day 1 to Day 16 plus pegylated interferon alpha-2a (PegIFN-alpha-2a) 180 micrograms (mcg) SC injection on Days 1, 8, and 15.
Percentage of Participants With Biochemical Flares	0 Percentage of participants

SECONDARY outcome

Timeframe: Up to 72 weeks

Population: FAS included all participants who were randomly assigned to an intervention arm in the ISA and received at least 1 dose of study intervention. The data was not collected and analyzed for this outcome measure due to premature termination of the study.

Percentage of participants requiring NA re-treatment were planned to be reported.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Up to 72 weeks

Population: FAS included all participants who were randomly assigned to an intervention arm in the ISA and received at least 1 dose of study intervention. The data was not collected and analyzed for this outcome measure due to premature termination of the study.

Percentage of participants with HBsAg, HBeAg, HBV DNA, and ALT levels below/above different cut-offs were planned to be reported.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Up to 72 weeks

Population: FAS included all participants who were randomly assigned to an intervention arm in the ISA and received at least 1 dose of study intervention. The data was not collected and analyzed for this outcome measure due to premature termination of the study.

Percentage of participants with HBsAg seroconversion were planned to be reported. Seroconversion of HBsAg is defined as having achieved HBsAg seroclearance (quantitative HBsAg level \<LLOQ) and appearance of anti-HBs antibodies. LLOQ is 0.05 IU/mL.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline up to Week 72

Population: FAS included all participants who were randomly assigned to an intervention arm in the ISA and received at least 1 dose of study intervention. The data was not collected and analyzed for this outcome measure due to premature termination of the study.

Change from baseline in HBsAg over time were planned to be reported.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Up to 72 weeks

Population: FAS included all participants who were randomly assigned to an intervention arm in the ISA and received at least 1 dose of study intervention. The data was not collected and analyzed for this outcome measure due to premature termination of the study.

Time to achieve HBsAg seroclearance were planned to be reported. Time to achieve HBsAg seroclearance is defined as the number of days between the date of first study intervention intake and the date of the first occurrence of HBsAg seroclearance (that is, the date of the first HBsAg seroclearance - the date of first study intervention intake + 1). Seroclearance of HBsAg is defined as a (quantitative) HBsAg level \<LLOQ. LLOQ is 0.05 IU/mL.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Up to 72 weeks

Population: FAS included all participants who were randomly assigned to an intervention arm in the ISA and received at least 1 dose of study intervention. The data was not collected and analyzed for this outcome measure due to premature termination of the study.

Time to achieve HBsAg seroconversion were planned to be reported. Time to achieve HBsAg seroconversion is defined as the number of days between the date of first study intervention intake and the date of the first occurrence of HBsAg seroclearance and appearance of anti-HBs antibodies (that is, the date of the first HBsAg seroclearance and anti-HBs antibodies - the date of first study intervention intake + 1). Seroconversion of HBsAg is defined as having achieved HBsAg seroclearance (quantitative HBsAg level \<LLOQ) and appearance of anti-HBs antibodies. LLOQ is 0.05 IU/mL.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Up to 72 weeks

Population: FAS included all participants who were randomly assigned to an intervention arm in the ISA and received at least 1 dose of study intervention. The data was not collected and analyzed for this outcome measure due to premature termination of the study.

Time to achieve HBV DNA \<LLOQ were planned to be reported. Time to achieve HBV DNA \<LLOQ is defined as the number of days between HBV DNA \>LLOQ for participants who re-treated with NA and the date of the first occurrence of HBV DNA \< LLOQ after NA re-treatment (that is, the date of the HBV DNA \< LLOQ after being re-treated with NA - the date of first occurrence of HBV DNA\>LLOQ + 1). LLOQ is 0.05 IU/mL.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Up to Week 24

Population: FAS included all participants who were randomly assigned to an intervention arm in the ISA and received at least 1 dose of study intervention. The data was not collected and analyzed for this outcome measure due to premature termination of the study.

Percentage of participants with virologic breakthrough were planned to be reported. HBV virological breakthrough is defined as having a confirmed on-treatment HBV DNA increase by \>1 log10 from nadir level (lowest level reached during treatment) in participants who did not have on-treatment HBV DNA level below the LLOQ or a confirmed on-treatment HBV DNA level \>200 IU/mL in participants who had on-treatment HBV DNA level below the LLOQ. LLOQ is 0.05 IU/mL.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Up to 72 weeks

Population: Pharmacokinetics (PK) analysis set included all participants who received at least 1 dose of study intervention and have at least 1 valid blood sample drawn for PK analysis. The data was not collected and analyzed for this outcome measure due to premature termination of the study.

Serum concentration of JNJ-73763989 (JNJ-73763924 and JNJ-73763976) were planned to be reported.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Up to 72 weeks

Population: PK analysis set included all participants who received at least 1 dose of study intervention and have at least 1 valid blood sample drawn for PK analysis. The data was not collected and analyzed for this outcome measure due to premature termination of the study.

Serum concentration of NA (ETV) was planned to be reported.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Up to 72 weeks

Population: PK analysis set included all participants who received at least 1 dose of study intervention and have at least 1 valid blood sample drawn for PK analysis. The data was not collected and analyzed for this outcome measure due to premature termination of the study.

Serum concentration of PegIFN-alpha-2a was planned to be reported.

Outcome measures

Outcome data not reported

Adverse Events

Arm 1: JNJ-73763989+Nucleos(t)Ide Analog (NA)+PegIFN-alpha-2a

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Study Director

Janssen Research & Development, LLC

Phone: 844-434-4210

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee If an investigator wishes to publish information from the study, a copy of the manuscript must be provided to the sponsor for review at least 60 days before submission for publication or presentation. If requested by the sponsor in writing, the investigator will withhold such publication for up to an additional 60 days to allow for filing of a patent application.
Publication restrictions are in place

Restriction type: OTHER