A Study of JNJ-73763989 + Nucleos(t)Ide Analog in Participants Co-Infected With Hepatitis B and Hepatitis D Virus

Hepatitis D, Chronic Clinical Trial

— REEF-D  

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04535544
• Other study ID #: CR108868
• Secondary ID: 2020-001249-3773
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: September 17, 2020
• Est. completion date: February 5, 2025

Study information

• Verified date: June 2024
• Source: Janssen Research & Development, LLC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 52
• Est. completion date: February 5, 2025
• Est. primary completion date: October 19, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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)

Related Conditions & MeSH terms

• Hepatitis
• Hepatitis A
• Hepatitis B
• Hepatitis D
• Hepatitis D, Chronic

Intervention

Drug:
• JNJ-73763989
JNJ-73763989 will be administered as a SC injection.
• Placebo
Matching placebo to JNJ-73763989 will be administered as a SC injection.
• Entecavir (ETV) monohydrate
ETV monohydrate film coated tablet will be administered orally.
• Tenofovir disoproxil
Tenofovir disoproxil film-coated tablet will be administered orally.
• Tenofovir alafenamide (TAF)
TAF film coated tablet will be administered orally.

Locations

Country	Name	City	State
Australia	Royal Prince Alfred Hospital	Camperdown
Australia	Western Health	Footscray
Australia	Westmead Hospital	Westmead
Brazil	Centro Oncológico De Roraima	Boa Vista
Brazil	Fundacao De Medicina Tropical Doutor Heitor Vieira Dourado	Manaus
Brazil	Cepem - Centro de Pesquisa Em Medicina Tropical	Porto Velho
China	Beijing Ditan Hospital Capical Medical University	Beijing
China	Peking University People s Hospital	Beijing
China	The First Bethune Hospital of Jilin University	Changchun
China	West China Hospital Sichuan University	Chengdu
China	The Second Affiliated Hospital of Chongqing Medical University	Chongqing
China	Guangzhou Eighth People's Hospital, Guangzhou Medical University	Guangzhou
China	Nanfang Hospital	Guangzhou
China	The First Affiliated Hospital Zhejiang University College of Medicine	Hangzhou
China	Huashan Hospital Fudan University	Shanghai
France	Hopital Beaujon	Clichy
France	Hopital de La Croix Rousse	Lyon
France	CHU de Nantes hotel Dieu	Nantes
France	CHU Hopital Saint Antoine	Paris
France	Chu Rennes Hopital Pontchaillou	Rennes
Germany	Universitatsklinikum Essen	Essen
Germany	Universitätsklinikum Johann Wolfgang Goethe- Universität Frankfurt Medizinische Klinik 1	Frankfurt
Germany	Medizinische Hochschule Hannover	Hannover
Italy	Irccs Ospedale Maggiore Di Milano	Milano
Italy	Azienda Ospedaliero Universitaria Pisana	Pisa
Italy	Universita degli Studi di Roma 'La Sapienza' - Umberto I Policlinico di Roma	Rome
Italy	Ospedale Molinette, AO Città della Salute e della Scienza di	Torino
Japan	Tokyo Medical and Dental University Hospital	Bunkyo Ku
Japan	Hiroshima Red Cross Hospital & Atomic-bomb Survivors Hospital	Hiroshima
Japan	Iizuka Hospital	Iizuka-shi
Japan	Ikeda City Hospital	Ikeda
Japan	Kumamoto Shinto General Hospital	Kumamoto
Japan	Kumamoto University Hospital	Kumamoto
Japan	Nagasaki University Hospital	Nagasaki
Japan	National Hospital Organization Nagasaki Medical Center	Nagasaki
Japan	University of the Ryukyus Hospital	Nakagami gun
Japan	Nakagami Hospital	Okinawa
Japan	Suita Municipal Hospital	Suita
Japan	Osaka University Hospital	Suita-shi
Japan	Tokyo Metropolitan Bokutoh Hospital	Sumida ku
New Zealand	New Zealand Clinical Research	Auckland
Russian Federation	Krasnoyarsk Regional Center For AIDS And Infectious Diseases Treatment And Prophylaxis	Krasnoyarsk
Russian Federation	St. Petersburg City Center for AIDS and Infectious Diseases Treatment and Prophylaxis	Saint Petersburg
Russian Federation	Medical Company Hepatolog Ltd	Samara
Spain	Hosp Clinic de Barcelona	Barcelona
Spain	Hosp. Univ. Vall D Hebron	Barcelona
Spain	Hosp. Univ. 12 de Octubre	Madrid
Spain	Hosp. Univ. Marques de Valdecilla	Santander
Sweden	Danderyds Sjukhus	Danderyd
Sweden	Skanes universitetssjukhus	Malmö
Sweden	Karolinska Universitetssjukhuset Huddinge	Stockholm
Taiwan	Kaohsiung Medical University Chung-Ho Memorial Hospital	Kaohsiung
Taiwan	National Taiwan University Hospital	Taipei
Taiwan	China Medical University Hospital	Tiachung
Turkey	Istanbul University Cerrahpasa Medical Faculty	Istanbul
Turkey	Ege University Medical of Faculty, Department of Gastroenterology	Izmir
Turkey	Kocaeli University Medical Faculty	Kocaeli
Turkey	Karadeniz Teknik University Medical Faculty	Trabzon
United Kingdom	Kings College Hospital	London
United States	Harvard Medical School Massachusetts General Hospital	Boston	Massachusetts
United States	Stanford University School of Medicine	Redwood City	California

Sponsors (1)

Lead Sponsor	Collaborator
Janssen Research & Development, LLC

Countries where clinical trial is conducted

United States,  Australia,  Brazil,  China,  France,  Germany,  Italy,  Japan,  New Zealand,  Russian Federation,  Spain,  Sweden,  Taiwan,  Turkey,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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.	Week 48
Secondary	Percentage of Participants with HDV RNA >=2 log10 IU/mL Decline From Baseline or HDV RNA TND at 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.	Week 48
Secondary	Percentage of Participants With Normal ALT at Week 48	Percentage of participants with normal ALT at Week 48 will be reported.	Week 48
Secondary	Percentage of Participants with HBsAg Seroclearance at Week 48	Percentage of participants with hepatitis B s antigen (HBsAg) seroclearance at Week 48 will be reported.	Week 48
Secondary	Percentage of Participants with >=2 kPa Reduction From Baseline in LSM assessed by VCTE (FibroScan) at 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.	Week 48
Secondary	Percentage of Participants with HDV RNA >=2 log10 IU/mL Decline From Baseline or HDV RNA TND in Combination with Normal ALT	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.	Baseline up to Week 196
Secondary	Percentage of Participants with HDV RNA >=2 log10 IU/mL Decline From Baseline in Combination with Normal ALT	Percentage of participants with HDV RNA >=2 log10 IU/mL decline from baseline in combination with normal ALT will be reported.	Up to Week 196
Secondary	Percentage of Participants with HDV RNA TND in Combination with Normal ALT	Percentage of participants with HDV RNA TND in combination with normal ALT will be reported.	Up to Week 196
Secondary	Percentage of Participants with HDV RNA >=2 log10 IU/mL Decline From Baseline or HDV RNA TND	Percentage of participants with HDV RNA >=2 log10 IU/mL decline from baseline or HDV RNA TND will be reported.	Up to Week 196
Secondary	Percentage of Participants with HDV RNA >=2 log10 IU/mL Decline From Baseline	Percentage of participants with HDV RNA >=2 log10 IU/mL decline from baseline will be reported.	Up to Week 196
Secondary	Percentage of Participants with HDV RNA TND	Percentage of participants with HDV RNA TND will be reported.	Up to Week 196
Secondary	Percentage of Participants with Normal ALT	Percentage of participants with normal ALT will be reported.	Up to Week 196
Secondary	Time to Reach HDV RNA >=2 log10 IU/mL Decline or HDV RNA TND	Time to reach HDV RNA >=2 log10 IU/mL decline or HDV RNA TND will be reported.	Up to Week 196
Secondary	Change from Baseline in HDV RNA	Change from baseline in HDV RNA will be reported.	Baseline and up to Week 196
Secondary	Changes from Baseline in ALT	Changes from baseline in ALT will be reported.	Baseline and up to Week 196
Secondary	Percentage of Participants with Adverse Events (AEs) and Serious AEs	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.	From screening up to Week 196
Secondary	Percentage of Participants with Abnormalities in Laboratory Parameters	Percentage of participants with abnormalities in laboratory parameters (hematology, blood biochemistry, blood coagulation, urinalysis, urine chemistry, and renal biomarkers) will be reported.	From screening up to Week 196
Secondary	Percentage of Participants with Abnormalities in 12-lead Electrocardiogram (ECGs)	Percentage of participants with abnormalities in 12-lead electrocardiogram (ECGs) will be reported.	From screening up to Week 196
Secondary	Percentage of Participants with Abnormalities in Vital Signs	Percentage of participants with abnormalities in vital signs (systolic and diastolic blood pressure, pulse rate, and body temperature) will be reported.	From screening up to Week 196
Secondary	Percentage of Participants with Abnormalities in Physical Examination	Percentage of participants with abnormalities in physical examination will be reported.	From screening up to Week 196
Secondary	Percentage of Participants with HBsAg Seroclearance and/or Seroconversion	Percentage of participants with HBsAg seroclearance and/or seroconversion will be reported.	Up to Week 196
Secondary	Change from Baseline Over Time in HBsAg	Change from baseline over time in HBsAg will be reported.	Baseline and up to Week 196
Secondary	Change from Baseline Over Time in HBeAg	Change from baseline over time in HBeAg will be reported.	Baseline and up to Week 196
Secondary	Change from Baseline Over Time in HBV DNA	Change from baseline over time in HBV DNA will be reported.	Baseline and up to Week 196
Secondary	Percentage of Participants with HBsAg levels below/above different cut-offs	Percentage of participants with HBsAg levels below/above different cut-offs will be reported.	Up to Week 196
Secondary	Percentage of Participants with HBeAg levels below/above different cut-offs	Percentage of participants with HBeAg levels below/above different cut-offs will be reported.	Up to Week 196
Secondary	Percentage of Participants with HBV DNA levels below/above different cut-offs	Percentage of participants with HBV DNA levels below/above different cut-offs will be reported.	Up to Week 196
Secondary	Percentage of Participants with HBsAg Change From Baseline Below/Above Different Cut-offs	Percentage of participants with HBsAg change from baseline below/above different cut-offs will be reported.	Baseline and up to Week 196
Secondary	Percentage of Participants with HBeAg Change From Baseline Below/Above Different Cut-offs	Percentage of participants with HBeAg change from baseline below/above different cut-offs will be reported.	Baseline and up to Week 196
Secondary	Percentage of Participants with HBV DNA Change From Baseline Below/Above Different Cut-offs	Percentage of participants with HBV DNA change from baseline below/above different cut-offs will be reported.	Baseline and up to Week 196
Secondary	Time to Reach Efficacy Thresholds such as HBsAg <1 IU/mL	Time to reach efficacy thresholds such as HBsAg <1 IU/mL will be reported.	Up to Week 196
Secondary	Percentage of Participants with HBV DNA Virologic Breakthrough	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.	Up to Week 196
Secondary	Percentage of Participants with >=2 kPa Reduction from Baseline in LSM Assessed by VCTE (FibroScan)	Percentage of participants with >=2 kPa reduction from baseline in LSM assessed by VCTE (FibroScan) will be reported.	Up to Week 196
Secondary	Change from Baseline in LSM Over Time Assessed by VCTE (FibroScan)	Change from baseline in LSM over time assessed by VCTE (FibroScan) will be reported.	Baseline and up to Week 196
Secondary	Percentage of Participants with Sustained HDV Response Off-treatment Post end of JNJ-73763989 Treatment	Percentage of participants with sustained HDV response off-treatment post end of JNJ-73763989 treatment will be reported.	Up to Week 196
Secondary	Percentage of Participants with HDV Relapse Post End of JNJ 73763989 Treatment	Percentage of participants with HDV relapse post end of JNJ 73763989 treatment will be reported.	Up to Week 196
Secondary	Percentage of Participants with Sustained HBV Response Off-Treatment Post End of JNJ-73763989 Treatment.	Percentage of participants with sustained HBV response off-treatment post end of JNJ-73763989 treatment will be reported.	Up to Week 196
Secondary	Percentage of Participants with HBV Flare (Virologic, Biochemical, and Clinical) Post End of Treatment	Percentage of participants with HBV flare (virologic, biochemical, and clinical) post end of treatment will be reported.	Up to Week 196