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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 (OCTOPUS-1)

Primary Purpose

Hepatitis B, Chronic

Status

Active

Phase

Phase 2

Locations

International

Study Type

Interventional

Intervention

JNJ-73763989

PD-1 inhibitor

Tenofovir Disoproxil

Tenofovir Alafenamide

Entecavir

About this trial

This is an interventional treatment trial for Hepatitis B, Chronic

Eligibility Criteria

18 Years - 55 Years (Adult)All SexesDoes not accept 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

Sites / Locations

Toronto General Hospital
Fakultni nemocnice Hradec Kralove
IKEM
Hopital Beaujon
Hopital Saint Joseph
Chu Rennes - Hopital Pontchaillou
CHRU Nancy-Brabois
Fondazione IRCCS Ca Granda, Ospedale Policlinico di Milano
Azienda Ospedaliero Universitaria Pisana
Universita degli Studi di Roma 'La Sapienza' - Umberto I Policlinico di Roma
Hosp. Univ. Vall D Hebron
Hosp. Univ. Pta. de Hierro Majadahonda
Hosp. Montecelo
Hosp. Gral. Univ. Valencia
Kaohsiung Medical University Chung-Ho Memorial Hospital
E-DA Hospital
China Medical University Hospital
Linkou Chang Gung Memorial Hospital
Hacettepe University Medical Faculty
Istanbul University Cerrahpasa Medical Faculty
Ege University Medical Faculty
Kocaeli University Medical Faculty
Karadeniz Teknik University Medical Faculty
Glasgow Royal Infirmary
King's College Hospital
Imperial College London and Imperial College Healthcare NHS Trust

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Arm Label

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

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

Arm Description

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]).

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).

Outcomes

Primary Outcome Measures

Percentage of Participants who Achieve Hepatitis B Surface Antigen (HBsAg) Seroclearance

Secondary Outcome Measures

Percentage of Participants who Experience Adverse Events (AEs) of Interest

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

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

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)

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

Percentage of Participants with Change in HBsAg Levels Below/Above Different Cut-offs Over Time

Percentage of Participants with HBsAg Seroclearance/Seroconversion

Time to Achieve HBsAg Seroclearance/ Seroconversion

Time to achieve HBsAg seroclearance/ seroconversion will be reported.

Change from Baseline in Hepatitis B Virus (HBV) Deoxyribonucleic Acid (DNA) Levels

Percentage of Participants with HBV DNA and Hepatitis B e Antigen (HBeAg) Levels Below/above Different Cut-offs

Percentage of participants with HBV DNA and HBeAg Levels below/above different cut-offs will be reported.

Percentage of Participants with Virologic Breakthrough

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)

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)

Plasma concentrations of NA (tenofovir disoproxil, TAF or ETV) will be reported.

Serum Concentrations of PD-1 Inhibitor (Optional)

Serum concentrations of PD-1 inhibitor will be reported.

Full Information

NCT ID

NCT05275023

First Posted

March 2, 2022

Last Updated

October 10, 2023

Sponsor

Janssen Research & Development, LLC

1. Study Identification

Unique Protocol Identification Number

NCT05275023

Brief Title

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

Acronym

OCTOPUS-1

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

Study Type

Interventional

2. Study Status

Record Verification Date

October 2023

Overall Recruitment Status

Active, not recruiting

Study Start Date

June 30, 2022 (Actual)

Primary Completion Date

December 13, 2023 (Anticipated)

Study Completion Date

May 29, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Janssen Research & Development, LLC

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

Yes

Data Monitoring Committee

5. 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.

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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Hepatitis B, Chronic

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

37 (Actual)

8. Arms, Groups, and Interventions

Arm Title

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

Arm Type

Experimental

Arm Description

Arm Title

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

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

JNJ-73763989

Other Intervention Name(s)

JNJ-3989

Intervention Description

JNJ-73763989 will be administered subcutaneously.

Intervention Type

Drug

Intervention Name(s)

PD-1 inhibitor

Intervention Description

PD-1 inhibitor will be administered as IV infusion.

Intervention Type

Drug

Intervention Name(s)

Tenofovir Disoproxil

Intervention Description

Tenofovir disoproxil film-coated tablets will be administered orally.

Intervention Type

Drug

Intervention Name(s)

Tenofovir Alafenamide

Intervention Description

TAF film-coated tablets will be administered orally.

Intervention Type

Drug

Intervention Name(s)

Entecavir

Intervention Description

ETV film-coated tablets will be administered orally.

Primary Outcome Measure Information:

Title

Percentage of Participants who Achieve Hepatitis B Surface Antigen (HBsAg) Seroclearance

Time Frame

Follow up Week 24

Secondary Outcome Measure Information:

Title

Percentage of Participants who Experience Adverse Events (AEs) of Interest

Description

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.

Time Frame

Up to Week 72

Title

Number of Participants with Adverse Events (AEs) by Severity

Description

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.

Time Frame

Up to Week 72

Title

Number of Participants with Immune Related Adverse Events (AEs) by Severity

Description

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.

Time Frame

Up to Week 72

Title

Number of Participants with Abnormalities in Vital Signs, Physical Examinations, Clinical Laboratory Tests, 12-lead Electrocardiograms (ECGs)

Description

Time Frame

Up to Week 72

Title

Change From Baseline in Hepatitis B Surface Antigen (HBsAg) Levels

Time Frame

Baseline up to Week 72

Title

Percentage of Participants with Change in HBsAg Levels Below/Above Different Cut-offs Over Time

Time Frame

Up to Week 72

Title

Percentage of Participants with HBsAg Seroclearance/Seroconversion

Time Frame

Up to Week 72

Title

Time to Achieve HBsAg Seroclearance/ Seroconversion

Description

Time to achieve HBsAg seroclearance/ seroconversion will be reported.

Time Frame

Up to Week 72

Title

Change from Baseline in Hepatitis B Virus (HBV) Deoxyribonucleic Acid (DNA) Levels

Time Frame

Baseline up to Week 72

Title

Percentage of Participants with HBV DNA and Hepatitis B e Antigen (HBeAg) Levels Below/above Different Cut-offs

Description

Percentage of participants with HBV DNA and HBeAg Levels below/above different cut-offs will be reported.

Time Frame

Up to Week 72

Title

Percentage of Participants with Virologic Breakthrough

Description

Time Frame

Up to Week 72

Title

Plasma Concentrations of JNJ-3989 and its Metabolites (JNJ-3924 and JNJ-3976)

Description

Plasma concentrations of JNJ-3989 and its metabolites (JNJ-3924 and JNJ-3976) will be reported.

Time Frame

Up to Week 24

Title

Plasma Concentrations of NA (Tenofovir disoproxil, Tenofovir Alafenamide [TAF] or Entecavir [ETV]) (Optional)

Description

Plasma concentrations of NA (tenofovir disoproxil, TAF or ETV) will be reported.

Time Frame

Up to Week 24

Title

Serum Concentrations of PD-1 Inhibitor (Optional)

Description

Serum concentrations of PD-1 inhibitor will be reported.

Time Frame

Up to Week 24

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

55 Years

Accepts Healthy Volunteers

Eligibility Criteria

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Janssen Research & Development, LLC Clinical Trial

Organizational Affiliation

Janssen Research & Development, LLC

Official's Role

Study Director

Facility Information:

Facility Name

Toronto General Hospital

City

Toronto

State/Province

Ontario

ZIP/Postal Code

M5G 2C4

Country

Canada

Facility Name

Fakultni nemocnice Hradec Kralove

City

Hradec Kralove

ZIP/Postal Code

500 05

Country

Czechia

Facility Name

IKEM

City

Prague 4

ZIP/Postal Code

140 21

Country

Czechia

Facility Name

Hopital Beaujon

City

Clichy

ZIP/Postal Code

92110

Country

France

Facility Name

Hopital Saint Joseph

City

Marseille

ZIP/Postal Code

13008

Country

France

Facility Name

Chu Rennes - Hopital Pontchaillou

City

Rennes

ZIP/Postal Code

35000

Country

France

Facility Name

CHRU Nancy-Brabois

City

Vandoeuvre-les-nancy

ZIP/Postal Code

54500

Country

France

Facility Name

Fondazione IRCCS Ca Granda, Ospedale Policlinico di Milano

City

Milano

ZIP/Postal Code

20122

Country

Italy

Facility Name

Azienda Ospedaliero Universitaria Pisana

City

Pisa

ZIP/Postal Code

56124

Country

Italy

Facility Name

Universita degli Studi di Roma 'La Sapienza' - Umberto I Policlinico di Roma

City

Rome

ZIP/Postal Code

00161

Country

Italy

Facility Name

Hosp. Univ. Vall D Hebron

City

Barcelona

ZIP/Postal Code

8035

Country

Spain

Facility Name

Hosp. Univ. Pta. de Hierro Majadahonda

City

Madrid

ZIP/Postal Code

28222

Country

Spain

Facility Name

Hosp. Montecelo

City

Pontevedra

ZIP/Postal Code

36071

Country

Spain

Facility Name

Hosp. Gral. Univ. Valencia

City

Valencia

ZIP/Postal Code

46014

Country

Spain

Facility Name

Kaohsiung Medical University Chung-Ho Memorial Hospital

City

Kaohsiung

ZIP/Postal Code

80756

Country

Taiwan

Facility Name

E-DA Hospital

City

Kaohsiung

ZIP/Postal Code

824

Country

Taiwan

Facility Name

China Medical University Hospital

City

Taichung

ZIP/Postal Code

40447

Country

Taiwan

Facility Name

Linkou Chang Gung Memorial Hospital

City

Taoyuan

ZIP/Postal Code

33305

Country

Taiwan

Facility Name

Hacettepe University Medical Faculty

City

Ankara

ZIP/Postal Code

06230

Country

Turkey

Facility Name

Istanbul University Cerrahpasa Medical Faculty

City

Istanbul

ZIP/Postal Code

34098

Country

Turkey

Facility Name

Ege University Medical Faculty

City

Izmir

ZIP/Postal Code

35040

Country

Turkey

Facility Name

Kocaeli University Medical Faculty

City

Kocaeli

ZIP/Postal Code

41001

Country

Turkey

Facility Name

Karadeniz Teknik University Medical Faculty

City

Trabzon

ZIP/Postal Code

61080

Country

Turkey

Facility Name

Glasgow Royal Infirmary

City

Glasgow

ZIP/Postal Code

G31 2ER

Country

United Kingdom

Facility Name

King's College Hospital

City

London

ZIP/Postal Code

SE5 9RS

Country

United Kingdom

Facility Name

Imperial College London and Imperial College Healthcare NHS Trust

City

London

ZIP/Postal Code

W2 1NY

Country

United Kingdom

12. IPD Sharing Statement

Plan to Share IPD

Yes

IPD Sharing Plan Description

The data sharing policy of the Janssen Pharmaceutical Companies of Johnson & Johnson is available at www.janssen.com/clinical-trials/transparency. As noted on this site, requests for access to the study data can be submitted through Yale Open Data Access (YODA) Project site at yoda.yale.edu

IPD Sharing URL

https://www.janssen.com/clinical-trials/transparency

Learn more about this trial

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

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