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)
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| ClinicalTrials.gov Identifier: NCT05275023 |
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Recruitment Status :
Active, not recruiting
First Posted : March 11, 2022
Last Update Posted : April 24, 2024
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Sponsor:
Janssen Research & Development, LLC
Information provided by (Responsible Party):
Janssen Research & Development, LLC
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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 |
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 Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 37 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 : | June 30, 2022 |
| Actual Primary Completion Date : | December 12, 2023 |
| Estimated Study Completion Date : | May 30, 2024 |
Resource links provided by the National Library of Medicine
| Arm | Intervention/treatment |
|---|---|
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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]).
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Drug: JNJ-73763989
JNJ-73763989 will be administered subcutaneously.
Other Name: 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. |
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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).
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Drug: JNJ-73763989
JNJ-73763989 will be administered subcutaneously.
Other Name: 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. |
Primary Outcome Measures :
- Percentage of Participants who Achieve Hepatitis B Surface Antigen (HBsAg) Seroclearance [ Time Frame: Follow up Week 24 ]
Secondary Outcome Measures :
- Percentage of Participants who Experience Adverse Events (AEs) of Interest [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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) [ Time Frame: 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 [ Time Frame: Baseline up to Week 72 ]
- Percentage of Participants with Change in HBsAg Levels Below/Above Different Cut-offs Over Time [ Time Frame: Up to Week 72 ]
- Percentage of Participants with HBsAg Seroclearance/Seroconversion [ Time Frame: Up to Week 72 ]
- Time to Achieve HBsAg Seroclearance/ Seroconversion [ Time Frame: 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 [ Time Frame: Baseline up to Week 72 ]
- Percentage of Participants with HBV DNA and Hepatitis B e Antigen (HBeAg) Levels Below/above Different Cut-offs [ Time Frame: 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 [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: Up to Week 24 ]Plasma concentrations of NA (tenofovir disoproxil, TAF or ETV) will be reported.
- Serum Concentrations of PD-1 Inhibitor (Optional) [ Time Frame: Up to Week 24 ]Serum concentrations of PD-1 inhibitor will be reported.
Information from the National Library of Medicine
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| Ages Eligible for Study: | 18 Years to 55 Years (Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
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
Information from the National Library of Medicine
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05275023
Locations
Show 26 study locations
Sponsors and Collaborators
Janssen Research & Development, LLC
Investigators
| Study Director: | Janssen Research & Development, LLC Clinical Trial | Janssen Research & Development, LLC |
| Responsible Party: | Janssen Research & Development, LLC |
| ClinicalTrials.gov Identifier: | NCT05275023 |
| Other Study ID Numbers: |
CR109161 2021-005132-33 ( EudraCT Number ) 73763989PAHPB2008 ( Other Identifier: Janssen Research & Development, LLC ) |
| First Posted: | March 11, 2022 Key Record Dates |
| Last Update Posted: | April 24, 2024 |
| Last Verified: | April 2024 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | Yes |
| 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 |
| URL: | https://www.janssen.com/clinical-trials/transparency |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
| Product Manufactured in and Exported from the U.S.: | Yes |
Additional relevant MeSH terms:
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Hepatitis A Hepatitis B Hepatitis B, Chronic Hepatitis Liver Diseases Digestive System Diseases Hepatitis, Viral, Human Virus Diseases Infections Enterovirus Infections Picornaviridae Infections RNA Virus Infections Blood-Borne Infections Communicable Diseases Hepadnaviridae Infections |
DNA Virus Infections Hepatitis, Chronic Chronic Disease Disease Attributes Pathologic Processes Tenofovir Entecavir Immune Checkpoint Inhibitors Antiviral Agents Anti-Infective Agents Reverse Transcriptase Inhibitors Nucleic Acid Synthesis Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Anti-HIV Agents |