OCTOPUS-1: An Efficacy and Safety Study of a Combination of JNJ-73763989, Nucleos(t)Ide Analogs (NA), and a Programmed Cell Death Protein Receptor-1 (PD-1) Inhibitor in Chronic Hepatitis B Participants

Sponsor

Janssen Research & Development, LLC (Industry)

Overall Status

Recruiting

CT.gov ID

NCT05275023

Collaborator

(none)

Enrollment

Locations

Arms

Anticipated Duration (Months)

1.4

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate efficacy of the study intervention, based on hepatitis B surface antigen (HBsAg) levels at follow-up (FU) Week 24.

Condition or Disease	Intervention/Treatment	Phase
Hepatitis B, Chronic	Drug: JNJ-73763989 Drug: PD-1 inhibitor Drug: Tenofovir Disoproxil Drug: Tenofovir Alafenamide Drug: Entecavir	Phase 2

Detailed Description

JNJ-73763989 (JNJ-3989) is a small interfering ribonucleic acid (siRNA) targeting all hepatitis B virus (HBV) messenger ribonucleic acid (mRNAs). The programmed cell death protein receptor-1 (PD-1) inhibitor aims at preventing the interaction of PD-1 with its ligands. The purpose of this study to determine whether at least one of the combination regimens of JNJ-3989 + PD-1 inhibitor + Nucleos(t)ide analog (NA) is more efficacious than JNJ-3989 + NA treatment. This study will be conducted in 3 periods: screening period, treatment period and follow-up (FU) period. Safety assessments will include adverse events (AEs), serious AEs, clinical safety laboratory tests, electrocardiograms (ECGs), vital signs, and physical examinations. Total duration of individual participation will be up to 78 weeks (including screening period).

Study Design

Study Type:

Interventional

Anticipated Enrollment :

44 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase 2 Open-label Trial to Evaluate Safety, Efficacy, Tolerability, and Pharmacodynamics of a Combination of JNJ-73763989, Nucleos(t)Ide Analogs, and a PD-1 Inhibitor in Chronic Hepatitis B Patients

Actual Study Start Date :

Jun 30, 2022

Anticipated Primary Completion Date :

Sep 12, 2023

Anticipated Study Completion Date :

May 29, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Arm 1: JNJ-73763989 + PD-1 Inhibitor + Nucleos(t)ide analog (NA) Participants will receive JNJ-73763989 subcutaneous (SC) injections and single dose of programmed cell death protein receptor-1 (PD-1) inhibitor as intravenous (IV) infusion. Participants will also receive background treatment with NA (either tenofovir disoproxil, tenofovir alafenamide [TAF] or entecavir [ETV]).	Drug: JNJ-73763989 JNJ-73763989 will be administered subcutaneously. Other Names: JNJ-3989 Drug: PD-1 inhibitor PD-1 inhibitor will be administered as IV infusion. Drug: Tenofovir Disoproxil Tenofovir disoproxil film-coated tablets will be administered orally. Drug: Tenofovir Alafenamide TAF film-coated tablets will be administered orally. Drug: Entecavir ETV film-coated tablets will be administered orally.
Experimental: Arm 2: JNJ-73763989 + PD-1 Inhibitor + NA Participants will receive JNJ-73763989 SC injections and multiple doses of PD-1 inhibitor as IV infusion. Participants will also receive background treatment with NA (either tenofovir disoproxil, TAF or ETV).	Drug: JNJ-73763989 JNJ-73763989 will be administered subcutaneously. Other Names: JNJ-3989 Drug: PD-1 inhibitor PD-1 inhibitor will be administered as IV infusion. Drug: Tenofovir Disoproxil Tenofovir disoproxil film-coated tablets will be administered orally. Drug: Tenofovir Alafenamide TAF film-coated tablets will be administered orally. Drug: Entecavir ETV film-coated tablets will be administered orally.

Arm

Intervention/Treatment

Experimental: Arm 1: JNJ-73763989 + PD-1 Inhibitor + Nucleos(t)ide analog (NA)

Participants will receive JNJ-73763989 subcutaneous (SC) injections and single dose of programmed cell death protein receptor-1 (PD-1) inhibitor as intravenous (IV) infusion. Participants will also receive background treatment with NA (either tenofovir disoproxil, tenofovir alafenamide [TAF] or entecavir [ETV]).

Drug: JNJ-73763989

JNJ-73763989 will be administered subcutaneously.

Other Names:

JNJ-3989

Drug: PD-1 inhibitor

PD-1 inhibitor will be administered as IV infusion.

Drug: Tenofovir Disoproxil

Tenofovir disoproxil film-coated tablets will be administered orally.

Drug: Tenofovir Alafenamide

TAF film-coated tablets will be administered orally.

Drug: Entecavir

ETV film-coated tablets will be administered orally.

Experimental: Arm 2: JNJ-73763989 + PD-1 Inhibitor + NA

Participants will receive JNJ-73763989 SC injections and multiple doses of PD-1 inhibitor as IV infusion. Participants will also receive background treatment with NA (either tenofovir disoproxil, TAF or ETV).

Drug: JNJ-73763989

JNJ-73763989 will be administered subcutaneously.

Other Names:

JNJ-3989

Drug: PD-1 inhibitor

PD-1 inhibitor will be administered as IV infusion.

Drug: Tenofovir Disoproxil

Tenofovir disoproxil film-coated tablets will be administered orally.

Drug: Tenofovir Alafenamide

TAF film-coated tablets will be administered orally.

Drug: Entecavir

ETV film-coated tablets will be administered orally.

Outcome Measures

Primary Outcome Measures

Percentage of Participants who Achieve Hepatitis B Surface Antigen (HBsAg) Seroclearance [Follow up Week 24]

Secondary Outcome Measures

Percentage of Participants who Experience Adverse Events (AEs) of Interest [Up to Week 72]
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. AEs of interest are significant AEs that are judged to be of special interest because of clinical importance, known class effects or based on nonclinical signals.
Number of Participants with Adverse Events (AEs) by Severity [Up to Week 72]
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. Severity of adverse event will be graded by using Division of AIDS (DAIDS) grading scale ranges from Grade 1 to Grade 5. Grade 1 indicates a mild event, Grade 2 indicates a moderate event, Grade 3 indicates a severe event, Grade 4 indicates a potentially life-threatening event, Grade 5 indicates death.
Number of Participants with Immune Related Adverse Events (AEs) by Severity [Up to Week 72]
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. Severity of immune related AEs will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0. Severity scale ranges from Grade 1 (Mild) to Grade 5 (Death). Grade 1= Mild, Grade 2= Moderate, Grade 3= Severe, Grade 4= Life-threatening and Grade 5= Death related to adverse event.
Number of Participants with Abnormalities in Vital Signs, Physical Examinations, Clinical Laboratory Tests, 12-lead Electrocardiograms (ECGs) [Up to Week 72]
Number of participants with abnormalities in vital sign measurements (including pulse rate and blood pressure, both systolic and diastolic); physical examinations (including height at screening, body weight, skin examination, general appearance, eyes, ears, nose, throat, cardiovascular system, respiratory system, gastro-intestinal system and mucous; clinical laboratory tests (including hematology, clinical chemistry and urinalysis); 12-lead ECGs (heart rate, PR, QRS, QT) will be reported.
Change From Baseline in Hepatitis B Surface Antigen (HBsAg) Levels [Baseline up to Week 72]
Percentage of Participants with Change in HBsAg Levels Below/Above Different Cut-offs Over Time [Up to Week 72]
Percentage of Participants with HBsAg Seroclearance/Seroconversion [Up to Week 72]
Time to Achieve HBsAg Seroclearance/ Seroconversion [Up to Week 72]
Time to achieve HBsAg seroclearance/ seroconversion will be reported.
Change from Baseline in Hepatitis B Virus (HBV) Deoxyribonucleic Acid (DNA) Levels [Baseline up to Week 72]
Percentage of Participants with HBV DNA and Hepatitis B e Antigen (HBeAg) Levels Below/above Different Cut-offs [Up to Week 72]
Percentage of participants with HBV DNA and HBeAg Levels below/above different cut-offs will be reported.
Percentage of Participants with Virologic Breakthrough [Up to Week 72]
Percentage of participants with virologic breakthrough (confirmed on-treatment HBV DNA increase by greater than [>]1 log10 international unit per milliliter [IU/mL] from nadir or confirmed on-treatment HBV DNA level >200 IU/mL in participants who had HBV DNA level less than [<] lower limit of quantification [LLOQ] of the HBV DNA assay) will be reported.
Plasma Concentrations of JNJ-3989 and its Metabolites (JNJ-3924 and JNJ-3976) [Up to Week 24]
Plasma concentrations of JNJ-3989 and its metabolites (JNJ-3924 and JNJ-3976) will be reported.
Plasma Concentrations of NA (Tenofovir disoproxil, Tenofovir Alafenamide [TAF] or Entecavir [ETV]) (Optional) [Up to Week 24]
Plasma concentrations of NA (tenofovir disoproxil, TAF or ETV) will be reported.
Serum Concentrations of PD-1 Inhibitor (Optional) [Up to Week 24]
Serum concentrations of PD-1 inhibitor will be reported.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 55 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Participants must have chronic hepatitis B virus (HBV) infection
Participants must have fibroscan liver stiffness measurement less than or equal to (<=) 9.0 kilopascal (kPa) or a liver biopsy result classified as metavir F0-F2

Exclusion Criteria:

Participants with evidence of hepatitis A virus infection (hepatitis A antibody immunoglobulin IgM), hepatitis C virus (HCV) infection (HCV antibody), hepatitis D virus (HDV) infection (HDV antibody), hepatitis E virus (HEV) infection (hepatitis E antibody IgM), or human immunodeficiency virus type 1 (HIV-1) or human immunodeficiency virus type 2 (HIV-2) infection (laboratory confirmed) 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
Participants with history or signs of cirrhosis or portal hypertension or signs of hepatocellular carcinoma (HCC) or clinically relevant renal abnormalities
Participants with personal/familial history/indicative of immune-mediated disease risk

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Vancouver ID Research and Care Centre Society	Vancouver	British Columbia	Canada	V6Z 2C7
2	Toronto General Hospital	Toronto	Ontario	Canada	M5G 2C4
3	Toronto General Hospital	Toronto	Ontario	Canada	M5G 2C4
4	Fakultni nemocnice Hradec Kralove	Hradec Kralove		Czechia	500 05
5	IKEM	Prague 4		Czechia	140 21
6	Hôpital Beaujon	Clichy		France	92110
7	Hopital Saint Joseph	Marseille		France	13008
8	Chu Rennes - Hopital Pontchaillou	Rennes		France	35000
9	CHRU Nancy-Brabois	Vandoeuvre-les-nancy		France	54500
10	Fondazione IRCCS Cà Granda, Ospedale Policlinico di Milano	Milano		Italy	20122
11	Azienda Ospedaliero Universitaria Pisana	Pisa		Italy	56124
12	Universita degli Studi di Roma 'La Sapienza' - Umberto I Policlinico di Roma	Rome		Italy	00161
13	St. Petersburg City Center for AIDS and Infectious Diseases Treatment and Prophylaxis	Saint Petersburg		Russian Federation	190103
14	Medical Company Hepatolog Ltd	Samara		Russian Federation	443045
15	Clinical Infectious Diseases Hospital n. a. S.P. Botkin	St. Petersburg		Russian Federation	195067
16	Research Institute of Influenza	St. Petersburg		Russian Federation	197376
17	Hosp. Univ. Vall D Hebron	Barcelona		Spain	8035
18	Hosp. Univ. Pta. de Hierro Majadahonda	Madrid		Spain	28222
19	Hosp. Montecelo	Pontevedra		Spain	36071
20	Hosp. Gral. Univ. Valencia	Valencia		Spain	46014
21	Kaohsiung Medical University Chung-Ho Memorial Hospital	Kaohsiung		Taiwan	80756
22	E-DA Hospital	Kaohsiung		Taiwan	824
23	China Medical University Hospital	Taichung		Taiwan	40447
24	Linkou Chang Gung Memorial Hospital	Taoyuan		Taiwan	33305
25	Hacettepe University Medical Faculty	Ankara		Turkey	06230
26	Istanbul University Cerrahpasa Medical Faculty	Istanbul		Turkey	34098
27	Ege University Medical Faculty	Izmir		Turkey	35040
28	Kocaeli University Medical Faculty	Kocaeli		Turkey	41001
29	Karadeniz Teknik University Medical Faculty	Trabzon		Turkey	61080
30	Glasgow Royal Infirmary	Glasgow		United Kingdom	G31 2ER
31	King's College Hospital	London		United Kingdom	SE5 9RS
32	Imperial College London and Imperial College Healthcare NHS Trust	London		United Kingdom	W2 1NY