A Study of Different Combination Regimens Including JNJ-73763989 and/or JNJ-56136379 for the Treatment of Chronic Hepatitis B Virus Infection (REEF-1)
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. |
ClinicalTrials.gov Identifier: NCT03982186 |
Recruitment Status :
Completed
First Posted : June 11, 2019
Last Update Posted : May 9, 2023
|
- Study Details
- Tabular View
- Results Submitted
- Disclaimer
- How to Read a Study Record
Condition or disease | Intervention/treatment | Phase |
---|---|---|
Hepatitis B, Chronic | Drug: JNJ-73763989 Drug: Placebo for JNJ-73763989 Drug: JNJ-56136379 Drug: Placebo for JNJ-56136379 Drug: Nucleos(t)ide Analog (NA) | Phase 2 |
Study Type : | Interventional (Clinical Trial) |
Actual Enrollment : | 471 participants |
Allocation: | Randomized |
Intervention Model: | Parallel Assignment |
Masking: | Double (Participant, Investigator) |
Primary Purpose: | Treatment |
Official Title: | A Phase 2b, Multicenter, Double-blind, Active-controlled, Randomized Study to Investigate the Efficacy and Safety of Different Combination Regimens Including JNJ-73763989 and/or JNJ-56136379 for the Treatment of Chronic Hepatitis B Virus Infection |
Actual Study Start Date : | August 1, 2019 |
Actual Primary Completion Date : | March 29, 2021 |
Actual Study Completion Date : | April 26, 2022 |
Arm | Intervention/treatment |
---|---|
Experimental: Arm 1: JNJ-73763989 (medium dose) + JNJ-56136379 + NA
Participants will receive medium dose of JNJ-73763989 along with JNJ-56136379 and nucleos(t)ide analog (NA) treatment (either entecavir [ETV], tenofovir disoproxil fumarate [TDF], or tenofovir alafenamide [TAF]) up to 48 weeks.
|
Drug: JNJ-73763989
JNJ-73763989 will be administered as medium dose (Arms 1 and 3), high dose (Arm 2), and low dose (Arm 4) as subcutaneous injection. Drug: JNJ-56136379 JNJ-56136379 tablets will be administered orally. Drug: Nucleos(t)ide Analog (NA) NA treatment that is either of ETV, TDF or TAF tablets will be administered orally. |
Experimental: Arm 2: JNJ-73763989 (high dose) + Placebo + NA
Participants will receive high dose of JNJ-73763989 along with placebo for JNJ-56136379 and NA (either ETV, TDF, or TAF) up to 48 weeks.
|
Drug: JNJ-73763989
JNJ-73763989 will be administered as medium dose (Arms 1 and 3), high dose (Arm 2), and low dose (Arm 4) as subcutaneous injection. Drug: Placebo for JNJ-56136379 Placebo for JNJ-56136379 tablets will be administered orally. Drug: Nucleos(t)ide Analog (NA) NA treatment that is either of ETV, TDF or TAF tablets will be administered orally. |
Experimental: Arm 3: JNJ-73763989 (medium dose) + Placebo + NA
Participants will receive medium dose of JNJ-73763989 along with placebo for JNJ-56136379 and NA (either ETV, TDF, or TAF) up to 48 weeks.
|
Drug: JNJ-73763989
JNJ-73763989 will be administered as medium dose (Arms 1 and 3), high dose (Arm 2), and low dose (Arm 4) as subcutaneous injection. Drug: Placebo for JNJ-56136379 Placebo for JNJ-56136379 tablets will be administered orally. Drug: Nucleos(t)ide Analog (NA) NA treatment that is either of ETV, TDF or TAF tablets will be administered orally. |
Experimental: Arm 4: JNJ-73763989 (low dose) + Placebo + NA
Participants will receive low dose of JNJ-73763989 along with placebo for JNJ-56136379 and NA (either ETV, TDF, or TAF) up to 48 weeks.
|
Drug: JNJ-73763989
JNJ-73763989 will be administered as medium dose (Arms 1 and 3), high dose (Arm 2), and low dose (Arm 4) as subcutaneous injection. Drug: Placebo for JNJ-56136379 Placebo for JNJ-56136379 tablets will be administered orally. Drug: Nucleos(t)ide Analog (NA) NA treatment that is either of ETV, TDF or TAF tablets will be administered orally. |
Experimental: Arm 5: Placebo + JNJ-56136379 + NA
Participants will receive placebo for JNJ-73763989 and a fixed dose of JNJ-56136379 along with NA (either ETV, TDF, or TAF) up to 48 weeks.
|
Drug: Placebo for JNJ-73763989
Placebo for JNJ-73763989 will be administered as subcutaneous injection. Drug: JNJ-56136379 JNJ-56136379 tablets will be administered orally. Drug: Nucleos(t)ide Analog (NA) NA treatment that is either of ETV, TDF or TAF tablets will be administered orally. |
Placebo Comparator: Arm 6 (Control): Placebo + Placebo + NA
Participants will receive placebo for JNJ-73763989 and placebo for JNJ-56136379 along with NA (either ETV, TDF, or TAF) up to 48 weeks.
|
Drug: Placebo for JNJ-73763989
Placebo for JNJ-73763989 will be administered as subcutaneous injection. Drug: Placebo for JNJ-56136379 Placebo for JNJ-56136379 tablets will be administered orally. Drug: Nucleos(t)ide Analog (NA) NA treatment that is either of ETV, TDF or TAF tablets will be administered orally. |
- Percentage of Participants Meeting the Nucleos(t)ide Analog (NA) Treatment Completion Criteria at Week 48 [ Time Frame: Week 48 ]Percentage of participants meeting the NA treatment completion criteria at week 48 will be reported.
- Number of Participants with Adverse Events (AE) and Serious Adverse Events (SAE) as a Measure of Safety and Tolerability [ Time Frame: Up to follow-up (maximum up to 150 weeks) ]An AE is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product. 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.
- Number of Participants with Abnormalities in Clinical Laboratory Tests, 12-Lead Electrocardiogram (ECG), and Vital Signs [ Time Frame: Up to follow-up (maximum up to 150 weeks) ]Number of participants with abnormalities in clinical laboratory tests, 12-lead ECG, and vital signs will be reported.
- Percentage of Participants with HBsAg Seroclearance After Completion of all Study Intervention [ Time Frame: Week 72 and Week 96 ]Percentage of participants with hepatitis B surface antigen (HBsAg) seroclearance after completion of all study intervention will be reported.
- Percentage of Participants with HBV DNA less than (<) Lower Limit of Quantification (LLOQ) After Completion of all Study Intervention [ Time Frame: Week 72 and Week 96 ]Percentage participants with hepatitis B virus (HBV) deoxyribonucleic acid (DNA) <LLOQ after completion of all study intervention will be reported.
- Percentage of Participants Meeting the NA Treatment Completion Criteria During Follow-up [ Time Frame: Up to 96 weeks ]Percentage of participants meeting the NA treatment completion criteria during follow-up will be reported.
- Percentage of Participants with HBsAg Seroclearance After Completion of NA Treatment at any Time During Follow-up [ Time Frame: Up to 150 weeks ]Percentage of participants with HBsAg seroclearance after completion of NA treatment at any time during follow-up will be reported.
- Percentage of Participants Requiring NA Re-treatment During Follow-up [ Time Frame: Up to 150 weeks ]Percentage of participants requiring NA re-treatment during follow-up will be reported.
- Percentage of Participants with Relapse [ Time Frame: Up to 150 weeks ]Percentage of participants with relapse will be reported.
- Percentage of Participants with (Sustained) Reduction, Suppression, and/or Seroclearance Considering Single and Multiple Markers [ Time Frame: Up to Week 96 ]Percentage of participants with (sustained) reduction, suppression, and/or seroclearance considering single and multiple markers (such as hepatitis B surface antigen [HBsAg], hepatitis B e antigen [HBeAg], HBV DNA and alanine aminotransferase [ALT]) will be reported.
- Percentage of Participants with HBsAg Seroconversion [ Time Frame: Up to 150 weeks ]Percentage of participants with HBsAg seroconversion will be reported.
- Percentage of Participants with HBeAg Seroconversion [ Time Frame: Up to 150 weeks ]Percentage of participants with HBeAg seroconversion will be reported.
- Change From Baseline in HBsAg Levels [ Time Frame: Baseline up to follow up (up to Week 150) ]Change from baseline in HBsAg levels will be determined.
- Change From Baseline in HBeAg Levels [ Time Frame: Baseline up to follow up (up to Week 150) ]Change from baseline in HBeAg levels will be determined.
- Change from Baseline in HBV DNA Levels [ Time Frame: Baseline up to follow up (up to Week 150) ]Change from baseline in HBV DNA levels will be determined.
- Time to Achieve HBsAg Seroclearance [ Time Frame: Up to Week 96 ]Time to achieve HBsAg seroclearance will be determined.
- Time to Achieve HBeAg Seroclearance [ Time Frame: Up to Week 96 ]Time to achieve HBeAg seroclearance will be determined.
- Percentage of Participants with <100 IU/mL or >1 log10 IU/mL Reduction in HBsAg From Baseline [ Time Frame: Baseline up to Week 150 ]Percentage of participants with less than (<) 100 international units per milliliter (IU/mL) or greater than (>) 1 log10 IU/mL reduction in HBsAg from baseline will be assessed.
- Percentage of HBeAg-positive Participants with HBeAg Levels [ Time Frame: Baseline up to Week 150 ]Percentage of HBeAg-positive participants with HBeAg levels will be reported.
- Percentage of Participants with ALT Decrease and Normalization [ Time Frame: Up to follow-up (maximum up to 150 weeks) ]Percentage of participants with alanine aminotransferase (ALT) decrease and normalization will be reported.
- Percentage of Participants with Virologic Breakthrough [ Time Frame: Up to Week 48 ]Percentage of participants with virologic breakthrough defined as confirmed on-treatment HBV DNA increase by >1 log10 IU/mL from nadir level or confirmed on treatment level >200 IU/mL in participants who had HBV DNA level below <LLOQ of the HBV DNA assay will be reported.
- Percentage of Participants with Undetectable HBV DNA Levels After Re-start of NA Treatment During Follow-up [ Time Frame: Up to 150 weeks ]Percentage of participants who reach HBV DNA undetectability after re-start of NA treatment during follow-up will be reported.
- Area Under the Plasma Concentration-time Curve over the Dosing Interval (tau) at Steady-state (AUCtau,ss) of JNJ-73763989 [ Time Frame: Days 1, 29, 85, 169 and 337 ]The AUC (tau,ss) is the area under the plasma concentration time curve observed during a dosing interval (tau) at steady state.
- Area Under the Plasma Concentration-time Curve over the Dosing Interval (tau) at Steady-state (AUCtau,ss) of JNJ-56136379 [ Time Frame: Days 1, 29, 85, 169 and 337 ]The AUC (tau,ss) is the area under the plasma concentration time curve observed during a dosing interval (tau) at steady state.
- Area Under the Plasma Concentration-time Curve over the Dosing Interval (tau) at Steady-state (AUCtau,ss) of NA [ Time Frame: Days 1, 29, 85, 169 and 337 ]The AUC (tau,ss) is the area under the plasma concentration time curve observed during a dosing interval (tau) at steady state.
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
Ages Eligible for Study: | 18 Years to 65 Years (Adult, Older Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- Medically stable based on physical examination, medical history, vital signs, electrocardiogram (ECG) at screening
- Chronic hepatitis B virus (HBV) infection with documentation at least 6 months prior to screening
- Hepatitis B surface antigen (HBsAg) greater than (>) 100 International Units per Milliliter (IU/mL) at screening
- 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
- Liver fibrosis stage 0-2 (Metavir) or Fibroscan less than (<) 9 Kilopascal (kPa) at screening
Exclusion Criteria:
- Evidence of infection with hepatitis A, C, D 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 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 and JNJ 6379 or their excipients or excipients of the placebo content
- Contraindications to the use of entecavir (ETV), tenofovir disoproxil fumarate (TDF), 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)
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): NCT03982186
Study Director: | Janssen Sciences Ireland UC Clinical Trial | Janssen Sciences Ireland UC |
Responsible Party: | Janssen Sciences Ireland UC |
ClinicalTrials.gov Identifier: | NCT03982186 |
Other Study ID Numbers: |
CR108608 2019-000622-22 ( EudraCT Number ) 73763989HPB2001 ( Other Identifier: Janssen Sciences Ireland UC ) |
First Posted: | June 11, 2019 Key Record Dates |
Last Update Posted: | May 9, 2023 |
Last Verified: | May 2023 |
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 |
Hepatitis A Hepatitis B Hepatitis B, Chronic Virus Diseases Herpesviridae Infections Hepatitis Infections Liver Diseases Digestive System Diseases Hepatitis, Viral, Human 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 JNJ-56136379 Antiviral Agents Anti-Infective Agents |