A Study of JNJ-73763989 + Nucleos(t)Ide Analog in Participants Co-Infected With Hepatitis B and Hepatitis D Virus (REEF-D)
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| ClinicalTrials.gov Identifier: NCT04535544 |
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Recruitment Status :
Active, not recruiting
First Posted : September 2, 2020
Last Update Posted : April 25, 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 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.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Hepatitis D, Chronic | Drug: JNJ-73763989 Drug: Placebo Drug: Entecavir (ETV) monohydrate Drug: Tenofovir disoproxil Drug: Tenofovir alafenamide (TAF) | Phase 2 |
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 52 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | Double (Participant, Investigator) |
| Primary Purpose: | Treatment |
| Official Title: | A Phase 2, Multicenter, Randomized, Double-blind, Placebo-Controlled Study With Deferred Active Treatment to Investigate the Efficacy, Safety, and Pharmacokinetics of JNJ-73763989 + Nucleos(t)Ide Analog in Participants Co-Infected With Hepatitis B and Hepatitis D Virus |
| Actual Study Start Date : | September 17, 2020 |
| Actual Primary Completion Date : | October 19, 2023 |
| Estimated Study Completion Date : | August 31, 2026 |
Resource links provided by the National Library of Medicine
| Arm | Intervention/treatment |
|---|---|
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Experimental: Immediate Active Treatment arm: JNJ-73763989 + NA
Participants will receive JNJ-73763989 subcutaneous (SC) injection every 4 weeks (Q4W) along with NA (entecavir [ETV], tenofovir disoproxil, or tenofovir alafenamide [TAF]) once daily for 144 Weeks in Part 1 and for at least 96 weeks in Part 2.
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Drug: JNJ-73763989
JNJ-73763989 will be administered as a SC injection.
Other Name: JNJ-3989 Drug: Entecavir (ETV) monohydrate ETV monohydrate film coated tablet will be administered orally. Drug: Tenofovir disoproxil Tenofovir disoproxil film-coated tablet will be administered orally. Drug: Tenofovir alafenamide (TAF) TAF film coated tablet will be administered orally. |
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Placebo Comparator: Deferred Active Treatment arm: Placebo+NA+JNJ-73763989+NA
Participants will receive matching placebo to JNJ-73763989 SC injection Q4W along with NA (ETV, tenofovir disoproxil, or TAF) once daily for 52 Weeks followed by JNJ-73763989 SC injection Q4W along with NA once daily for 96 weeks in Part 1 and for at least 48 weeks in Part 2.
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Drug: JNJ-73763989
JNJ-73763989 will be administered as a SC injection.
Other Name: JNJ-3989 Drug: Placebo Matching placebo to JNJ-73763989 will be administered as a SC injection. Drug: Entecavir (ETV) monohydrate ETV monohydrate film coated tablet will be administered orally. Drug: Tenofovir disoproxil Tenofovir disoproxil film-coated tablet will be administered orally. Drug: Tenofovir alafenamide (TAF) TAF film coated tablet will be administered orally. |
Primary Outcome Measures :
- 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 [ Time Frame: Week 48 ]Percentage of participants with hepatitis D virus (HDV) ribonucleic acid (RNA) greater than or equal to (>=) 2 log10 international units per milliliter (IU/mL) decline from baseline or HDV RNA target not detected (TND) in combination with normal alanine aminotransferase (ALT) at Week 48 will be reported.
Secondary Outcome Measures :
- Percentage of Participants with HDV RNA >=2 log10 IU/mL Decline From Baseline or HDV RNA TND at Week 48 [ Time Frame: Week 48 ]Percentage of participants with HDV RNA >=2 log10 IU/mL decline from baseline or HDV RNA TND at Week 48 will be reported.
- Percentage of Participants With Normal ALT at Week 48 [ Time Frame: Week 48 ]Percentage of participants with normal ALT at Week 48 will be reported.
- Percentage of Participants with HBsAg Seroclearance at Week 48 [ Time Frame: Week 48 ]Percentage of participants with hepatitis B s antigen (HBsAg) seroclearance at Week 48 will be reported.
- Percentage of Participants with >=2 kPa Reduction From Baseline in LSM assessed by VCTE (FibroScan) at Week 48 [ Time Frame: Week 48 ]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 will be reported.
- Percentage of Participants with HDV RNA >=2 log10 IU/mL Decline From Baseline or HDV RNA TND in Combination with Normal ALT [ Time Frame: Baseline up to Week 196 ]Percentage of participants with HDV RNA >=2 log10 IU/mL decline from baseline or HDV RNA TND in combination with normal ALT will be reported.
- Percentage of Participants with HDV RNA >=2 log10 IU/mL Decline From Baseline in Combination with Normal ALT [ Time Frame: Up to Week 196 ]Percentage of participants with HDV RNA >=2 log10 IU/mL decline from baseline in combination with normal ALT will be reported.
- Percentage of Participants with HDV RNA TND in Combination with Normal ALT [ Time Frame: Up to Week 196 ]Percentage of participants with HDV RNA TND in combination with normal ALT will be reported.
- Percentage of Participants with HDV RNA >=2 log10 IU/mL Decline From Baseline or HDV RNA TND [ Time Frame: Up to Week 196 ]Percentage of participants with HDV RNA >=2 log10 IU/mL decline from baseline or HDV RNA TND will be reported.
- Percentage of Participants with HDV RNA >=2 log10 IU/mL Decline From Baseline [ Time Frame: Up to Week 196 ]Percentage of participants with HDV RNA >=2 log10 IU/mL decline from baseline will be reported.
- Percentage of Participants with HDV RNA TND [ Time Frame: Up to Week 196 ]Percentage of participants with HDV RNA TND will be reported.
- Percentage of Participants with Normal ALT [ Time Frame: Up to Week 196 ]Percentage of participants with normal ALT will be reported.
- Time to Reach HDV RNA >=2 log10 IU/mL Decline or HDV RNA TND [ Time Frame: Up to Week 196 ]Time to reach HDV RNA >=2 log10 IU/mL decline or HDV RNA TND will be reported.
- Change from Baseline in HDV RNA [ Time Frame: Baseline and up to Week 196 ]Change from baseline in HDV RNA will be reported.
- Changes from Baseline in ALT [ Time Frame: Baseline and up to Week 196 ]Changes from baseline in ALT will be reported.
- Percentage of Participants with Adverse Events (AEs) and Serious AEs [ Time Frame: From screening up to Week 196 ]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. A 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.
- Percentage of Participants with Abnormalities in Laboratory Parameters [ Time Frame: From screening up to Week 196 ]Percentage of participants with abnormalities in laboratory parameters (hematology, blood biochemistry, blood coagulation, urinalysis, urine chemistry, and renal biomarkers) will be reported.
- Percentage of Participants with Abnormalities in 12-lead Electrocardiogram (ECGs) [ Time Frame: From screening up to Week 196 ]Percentage of participants with abnormalities in 12-lead electrocardiogram (ECGs) will be reported.
- Percentage of Participants with Abnormalities in Vital Signs [ Time Frame: From screening up to Week 196 ]Percentage of participants with abnormalities in vital signs (systolic and diastolic blood pressure, pulse rate, and body temperature) will be reported.
- Percentage of Participants with Abnormalities in Physical Examination [ Time Frame: From screening up to Week 196 ]Percentage of participants with abnormalities in physical examination will be reported.
- Percentage of Participants with HBsAg Seroclearance and/or Seroconversion [ Time Frame: Up to Week 196 ]Percentage of participants with HBsAg seroclearance and/or seroconversion will be reported.
- Change from Baseline Over Time in HBsAg [ Time Frame: Baseline and up to Week 196 ]Change from baseline over time in HBsAg will be reported.
- Change from Baseline Over Time in HBeAg [ Time Frame: Baseline and up to Week 196 ]Change from baseline over time in HBeAg will be reported.
- Change from Baseline Over Time in HBV DNA [ Time Frame: Baseline and up to Week 196 ]Change from baseline over time in HBV DNA will be reported.
- Percentage of Participants with HBsAg levels below/above different cut-offs [ Time Frame: Up to Week 196 ]Percentage of participants with HBsAg levels below/above different cut-offs will be reported.
- Percentage of Participants with HBeAg levels below/above different cut-offs [ Time Frame: Up to Week 196 ]Percentage of participants with HBeAg levels below/above different cut-offs will be reported.
- Percentage of Participants with HBV DNA levels below/above different cut-offs [ Time Frame: Up to Week 196 ]Percentage of participants with HBV DNA levels below/above different cut-offs will be reported.
- Percentage of Participants with HBsAg Change From Baseline Below/Above Different Cut-offs [ Time Frame: Baseline and up to Week 196 ]Percentage of participants with HBsAg change from baseline below/above different cut-offs will be reported.
- Percentage of Participants with HBeAg Change From Baseline Below/Above Different Cut-offs [ Time Frame: Baseline and up to Week 196 ]Percentage of participants with HBeAg change from baseline below/above different cut-offs will be reported.
- Percentage of Participants with HBV DNA Change From Baseline Below/Above Different Cut-offs [ Time Frame: Baseline and up to Week 196 ]Percentage of participants with HBV DNA change from baseline below/above different cut-offs will be reported.
- Time to Reach Efficacy Thresholds such as HBsAg <1 IU/mL [ Time Frame: Up to Week 196 ]Time to reach efficacy thresholds such as HBsAg <1 IU/mL will be reported.
- Percentage of Participants with HBV DNA Virologic Breakthrough [ Time Frame: Up to Week 196 ]Percentage of participants with virologic breakthrough (defined as confirmed on-treatment HBV DNA increase by greater than [>] 1 log10 IU/mL from nadir level or confirmed on treatment level >200 IU/mL in participants who had HBV DNA level below < lower limit of quantification [LLOQ] of the HBV DNA assay) will be reported.
- Percentage of Participants with >=2 kPa Reduction from Baseline in LSM Assessed by VCTE (FibroScan) [ Time Frame: Up to Week 196 ]Percentage of participants with >=2 kPa reduction from baseline in LSM assessed by VCTE (FibroScan) will be reported.
- Change from Baseline in LSM Over Time Assessed by VCTE (FibroScan) [ Time Frame: Baseline and up to Week 196 ]Change from baseline in LSM over time assessed by VCTE (FibroScan) will be reported.
- Percentage of Participants with Sustained HDV Response Off-treatment Post end of JNJ-73763989 Treatment [ Time Frame: Up to Week 196 ]Percentage of participants with sustained HDV response off-treatment post end of JNJ-73763989 treatment will be reported.
- Percentage of Participants with HDV Relapse Post End of JNJ 73763989 Treatment [ Time Frame: Up to Week 196 ]Percentage of participants with HDV relapse post end of JNJ 73763989 treatment will be reported.
- Percentage of Participants with Sustained HBV Response Off-Treatment Post End of JNJ-73763989 Treatment. [ Time Frame: Up to Week 196 ]Percentage of participants with sustained HBV response off-treatment post end of JNJ-73763989 treatment will be reported.
- Percentage of Participants with HBV Flare (Virologic, Biochemical, and Clinical) Post End of Treatment [ Time Frame: Up to Week 196 ]Percentage of participants with HBV flare (virologic, biochemical, and clinical) post end of treatment will be reported.
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| Ages Eligible for Study: | 18 Years to 65 Years (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Criteria
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)
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): NCT04535544
Locations
Show 61 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: | NCT04535544 |
| Other Study ID Numbers: |
CR108868 2020-001249-37 ( EudraCT Number ) 73763989HPB2004 ( Other Identifier: Janssen Research & Development, LLC ) 2023-506763-33-00 ( Registry Identifier: EUCT number ) |
| First Posted: | September 2, 2020 Key Record Dates |
| Last Update Posted: | April 25, 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 |
Additional relevant MeSH terms:
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Hepatitis A Hepatitis B Hepatitis D Hepatitis D, 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 Antiviral Agents Anti-Infective Agents Reverse Transcriptase Inhibitors Nucleic Acid Synthesis Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Anti-HIV Agents |