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Trial record 1 of 1 for:    NCT04535544
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A Study of JNJ-73763989 + Nucleos(t)Ide Analog in Participants Co-Infected With Hepatitis B and Hepatitis D Virus (REEF-D)

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. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04535544
Recruitment Status : Recruiting
First Posted : September 2, 2020
Last Update Posted : November 23, 2022
Sponsor:
Information provided by (Responsible Party):
Janssen Research & Development, LLC

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

Detailed Description:
JNJ-73763989 is a liver-targeted antiviral therapeutic for subcutaneous injection designed to treat chronic hepatitis B virus (HBV) infection via ribonucleic acid interference mechanism. This phase 2 study is designed to evaluate safety and efficacy of JNJ-73763989 in HBV infected patients who are co-infected with HDV. The study consists of 2 parts: Part 1 will evaluate safety, tolerability and antiviral activity of JNJ-73763989 + NA while Part 2 will evaluate the safety and efficacy of the JNJ-73763989 + NA regimen in the treatment of HBV/HDV co-infection. Each part includes 3 phases: Screening phase (from 4 Week up to maximum of 8 weeks), Intervention phase (144 Week for Arm A and 148 Week for Arm B) and Follow-up phase (48 Week). The duration of individual study participation will be between 196 and 204 weeks. Safety and tolerability (including adverse events [AEs] and Serious AEs, laboratory assessments, electrocardiogram [ECG], vital signs, physical examination), efficacy (including HDV ribonucleic acid [RNA], HBV deoxyribonucleic acid [DNA] and antigens) , and pharmacokinetics will be assessed throughout the study.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 190 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
Estimated Primary Completion Date : June 7, 2023
Estimated Study Completion Date : July 30, 2027


Arm Intervention/treatment
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 2.
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.

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 2.
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 :
  1. 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 :
  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. Percentage of Participants with HDV RNA >=2 log10 IU/mL Decline From Baseline or HDV RNA TND in Combination with Normal ALT [ Time Frame: Up to Week 204 ]
    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.

  6. Percentage of Participants with HDV RNA >=2 log10 IU/mL Decline From Baseline in Combination with Normal ALT [ Time Frame: Up to Week 204 ]
    Percentage of participants with HDV RNA >=2 log10 IU/mL decline from baseline in combination with normal ALT will be reported.

  7. Percentage of Participants with HDV RNA TND in Combination with Normal ALT [ Time Frame: Up to Week 204 ]
    Percentage of participants with HDV RNA TND in combination with normal ALT will be reported.

  8. Percentage of Participants with HDV RNA >=2 log10 IU/mL Decline From Baseline or HDV RNA TND [ Time Frame: Up to Week 204 ]
    Percentage of participants with HDV RNA >=2 log10 IU/mL decline from baseline or HDV RNA TND will be reported.

  9. Percentage of Participants with HDV RNA >=2 log10 IU/mL Decline From Baseline [ Time Frame: Up to Week 204 ]
    Percentage of participants with HDV RNA >=2 log10 IU/mL decline from baseline will be reported.

  10. Percentage of Participants with HDV RNA TND [ Time Frame: Up to Week 204 ]
    Percentage of participants with HDV RNA TND will be reported.

  11. Percentage of Participants with Normal ALT [ Time Frame: Up to Week 204 ]
    Percentage of participants with normal ALT will be reported.

  12. Time to Reach HDV RNA >=2 log10 IU/mL Decline or HDV RNA TND [ Time Frame: Up to Week 204 ]
    Time to reach HDV RNA >=2 log10 IU/mL decline or HDV RNA TND will be reported.

  13. Change from Baseline in HDV RNA [ Time Frame: Baseline and up to Week 204 ]
    Change from baseline in HDV RNA will be reported.

  14. Changes from Baseline in ALT [ Time Frame: Baseline and up to Week 204 ]
    Changes from baseline in ALT will be reported.

  15. Percentage of Participants with Adverse Events (AEs) and Serious AEs [ Time Frame: Up to Week 204 ]
    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.

  16. Percentage of Participants with Abnormalities in Laboratory Parameters [ Time Frame: Up to Week 204 ]
    Percentage of participants with abnormalities in laboratory parameters (hematology, blood biochemistry, blood coagulation, urinalysis, urine chemistry, and renal biomarkers) will be reported.

  17. Percentage of Participants with Abnormalities in 12-lead Electrocardiogram (ECGs) [ Time Frame: Up to Week 204 ]
    Percentage of participants with abnormalities in 12-lead electrocardiogram (ECGs) will be reported.

  18. Percentage of Participants with Abnormalities in Vital Signs [ Time Frame: Up to Week 204 ]
    Percentage of participants with abnormalities in vital signs (systolic and diastolic blood pressure, pulse rate, and body temperature) will be reported.

  19. Percentage of Participants with Abnormalities in Physical Examination [ Time Frame: Up to Week 204 ]
    Percentage of participants with abnormalities in physical examination will be reported.

  20. Percentage of Participants with HBsAg Seroclearance and/or Seroconversion [ Time Frame: Up to Week 204 ]
    Percentage of participants with HBsAg seroclearance and/or seroconversion will be reported.

  21. Change from Baseline Over Time in HBsAg [ Time Frame: Baseline and up to Week 204 ]
    Change from baseline over time in HBsAg will be reported.

  22. Change from Baseline Over Time in HBeAg [ Time Frame: Baseline and up to Week 204 ]
    Change from baseline over time in HBeAg will be reported.

  23. Change from Baseline Over Time in HBV DNA [ Time Frame: Baseline and up to Week 204 ]
    Change from baseline over time in HBV DNA will be reported.

  24. Percentage of Participants with HBsAg levels below/above different cut-offs [ Time Frame: Up to Week 204 ]
    Percentage of participants with HBsAg levels below/above different cut-offs will be reported.

  25. Percentage of Participants with HBeAg levels below/above different cut-offs [ Time Frame: Up to Week 204 ]
    Percentage of participants with HBeAg levels below/above different cut-offs will be reported.

  26. Percentage of Participants with HBV DNA levels below/above different cut-offs [ Time Frame: Up to Week 204 ]
    Percentage of participants with HBV DNA levels below/above different cut-offs will be reported.

  27. Percentage of Participants with HBsAg Change From Baseline Below/Above Different Cut-offs [ Time Frame: Baseline and up to Week 204 ]
    Percentage of participants with HBsAg change from baseline below/above different cut-offs will be reported.

  28. Percentage of Participants with HBeAg Change From Baseline Below/Above Different Cut-offs [ Time Frame: Baseline and up to Week 204 ]
    Percentage of participants with HBeAg change from baseline below/above different cut-offs will be reported.

  29. Percentage of Participants with HBV DNA Change From Baseline Below/Above Different Cut-offs [ Time Frame: Baseline and up to Week 204 ]
    Percentage of participants with HBV DNA change from baseline below/above different cut-offs will be reported.

  30. Time to Reach Efficacy Thresholds such as HBsAg <1 IU/mL [ Time Frame: Up to Week 204 ]
    Time to reach efficacy thresholds such as HBsAg <1 IU/mL will be reported.

  31. Percentage of Participants with HBV DNA Virologic Breakthrough [ Time Frame: Up to Week 204 ]
    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.

  32. Area Under the Plasma Concentration-time Curve (AUC) of JNJ-73763989 and Optionally NA [ Time Frame: Up to Week 124 ]
    Area under the plasma concentration-time curve (AUC) of JNJ-73763989 and optionally NA will be reported.

  33. Percentage of Participants with >=2 kPa Reduction from Baseline in LSM Assessed by VCTE (FibroScan) [ Time Frame: Up to Week 204 ]
    Percentage of participants with >=2 kPa reduction from baseline in LSM assessed by VCTE (FibroScan) will be reported.

  34. Change from Baseline in LSM Over Time Assessed by VCTE (FibroScan) [ Time Frame: Baseline and up to Week 204 ]
    Change from baseline in LSM over time assessed by VCTE (FibroScan) will be reported.

  35. Percentage of Participants with Sustained HDV Response Off-treatment Post end of JNJ-73763989 Treatment [ Time Frame: Up to Week 204 ]
    Percentage of participants with sustained HDV response off-treatment post end of JNJ-73763989 treatment will be reported.

  36. Percentage of Participants with HDV Relapse Post End of JNJ 73763989 Treatment [ Time Frame: Up to Week 204 ]
    Percentage of participants with HDV relapse post end of JNJ 73763989 treatment will be reported.

  37. Percentage of Participants with Sustained HBV Response Off-Treatment Post End of JNJ-73763989 Treatment. [ Time Frame: Up to Week 204 ]
    Percentage of participants with sustained HBV response off-treatment post end of JNJ-73763989 treatment will be reported.

  38. Percentage of Participants with HBV Flare (Virologic, Biochemical, and Clinical) Post End of Treatment [ Time Frame: Up to Week 204 ]
    Percentage of participants with HBV flare (virologic, biochemical, and clinical) post end of treatment will be reported.

  39. Change from Baseline in Hepatitis B Quality of Life (HBQOL) Scale And Subscales [ Time Frame: Baseline and up to Week 204 ]
    HBQOL is a 31-item disease-specific instrument designed to measure HRQOL for participants with chronic hepatitis B (CHB). Score ranges from 0 to 100, where lower scores denote less Health-related Quality of Life (HRQOL) impact, and higher scores denote more HRQOL impact (that is 0=best score and 100=worst score).



Information from the National Library of Medicine

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.


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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 (<=) 10,000 IU/mL at screening or HDV RNA values at screening are <= 100,000 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 >= 140,000 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


Contacts
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Contact: Study Contact 844-434-4210 Participate-In-This-Study@its.jnj.com

Locations
Show Show 81 study locations
Sponsors and Collaborators
Janssen Research & Development, LLC
Investigators
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Study Director: Janssen Research & Development, LLC Clinical Trial Janssen Research & Development, LLC
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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 )
First Posted: September 2, 2020    Key Record Dates
Last Update Posted: November 23, 2022
Last Verified: November 2022
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

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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
Tenofovir
Entecavir
Antiviral Agents
Anti-Infective Agents
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-HIV Agents
Anti-Retroviral Agents