REEF-D: A Study of JNJ-73763989 + Nucleos(t)Ide Analog in Participants Co-Infected With Hepatitis B and Hepatitis D Virus
Study Details
Study Description
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 |
|---|---|---|
|
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.
Study Design
Arms and Interventions
| 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 Names:
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 Names:
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.
|
Outcome Measures
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 [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 [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 [Week 48]
Percentage of participants with normal ALT at Week 48 will be reported.
- Percentage of Participants with HBsAg Seroclearance at Week 48 [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 [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 [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.
- Percentage of Participants with HDV RNA >=2 log10 IU/mL Decline From Baseline in Combination with Normal ALT [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.
- Percentage of Participants with HDV RNA TND in Combination with Normal ALT [Up to Week 204]
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 [Up to Week 204]
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 [Up to Week 204]
Percentage of participants with HDV RNA >=2 log10 IU/mL decline from baseline will be reported.
- Percentage of Participants with HDV RNA TND [Up to Week 204]
Percentage of participants with HDV RNA TND will be reported.
- Percentage of Participants with Normal ALT [Up to Week 204]
Percentage of participants with normal ALT will be reported.
- Time to Reach HDV RNA >=2 log10 IU/mL Decline or HDV RNA TND [Up to Week 204]
Time to reach HDV RNA >=2 log10 IU/mL decline or HDV RNA TND will be reported.
- Change from Baseline in HDV RNA [Baseline and up to Week 204]
Change from baseline in HDV RNA will be reported.
- Changes from Baseline in ALT [Baseline and up to Week 204]
Changes from baseline in ALT will be reported.
- Percentage of Participants with Adverse Events (AEs) and Serious AEs [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.
- Percentage of Participants with Abnormalities in Laboratory Parameters [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.
- Percentage of Participants with Abnormalities in 12-lead Electrocardiogram (ECGs) [Up to Week 204]
Percentage of participants with abnormalities in 12-lead electrocardiogram (ECGs) will be reported.
- Percentage of Participants with Abnormalities in Vital Signs [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.
- Percentage of Participants with Abnormalities in Physical Examination [Up to Week 204]
Percentage of participants with abnormalities in physical examination will be reported.
- Percentage of Participants with HBsAg Seroclearance and/or Seroconversion [Up to Week 204]
Percentage of participants with HBsAg seroclearance and/or seroconversion will be reported.
- Change from Baseline Over Time in HBsAg [Baseline and up to Week 204]
Change from baseline over time in HBsAg will be reported.
- Change from Baseline Over Time in HBeAg [Baseline and up to Week 204]
Change from baseline over time in HBeAg will be reported.
- Change from Baseline Over Time in HBV DNA [Baseline and up to Week 204]
Change from baseline over time in HBV DNA will be reported.
- Percentage of Participants with HBsAg levels below/above different cut-offs [Up to Week 204]
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 [Up to Week 204]
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 [Up to Week 204]
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 [Baseline and up to Week 204]
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 [Baseline and up to Week 204]
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 [Baseline and up to Week 204]
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 [Up to Week 204]
Time to reach efficacy thresholds such as HBsAg <1 IU/mL will be reported.
- Percentage of Participants with HBV DNA Virologic Breakthrough [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.
- Area Under the Plasma Concentration-time Curve (AUC) of JNJ-73763989 and Optionally NA [Up to Week 124]
Area under the plasma concentration-time curve (AUC) of JNJ-73763989 and optionally NA will be reported.
- Percentage of Participants with >=2 kPa Reduction from Baseline in LSM Assessed by VCTE (FibroScan) [Up to Week 204]
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) [Baseline and up to Week 204]
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 [Up to Week 204]
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 [Up to Week 204]
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. [Up to Week 204]
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 [Up to Week 204]
Percentage of participants with HBV flare (virologic, biochemical, and clinical) post end of treatment will be reported.
- Change from Baseline in Hepatitis B Quality of Life (HBQOL) Scale And Subscales [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).
Eligibility Criteria
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)
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Ruane Clinical Research Group Inc | Los Angeles | California | United States | 90036 |
| 2 | Cedars Sinai Medical Center | Los Angeles | California | United States | 90048 |
| 3 | Stanford University School of Medicine | Redwood City | California | United States | 94063 |
| 4 | Southern California GI and Liver Center | San Clemente | California | United States | 92673 |
| 5 | Johns Hopkins University School of Medicine | Lutherville | Maryland | United States | 21093 |
| 6 | Harvard Medical School - Massachusetts General Hospital | Boston | Massachusetts | United States | 02114 |
| 7 | I.D. Care, Inc. | Hillsborough | New Jersey | United States | 08844 |
| 8 | Eastern Health Research | Box Hill | Australia | 3128 | |
| 9 | Royal Prince Alfred Hospital | Camperdown | Australia | 2050 | |
| 10 | Western Health | Footscray | Australia | 3011 | |
| 11 | Westmead Hospital | Westmead | Australia | 2145 | |
| 12 | Centro Oncológico De Roraima | Boa Vista | Brazil | 69304015 | |
| 13 | Fundação De Medicina Tropical Doutor Heitor Vieira Dourado | Manaus | Brazil | 69040-000 | |
| 14 | Cepem - Centro de Pesquisa Em Medicina Tropical | Porto Velho | Brazil | 76812-329 | |
| 15 | Beijing Ditan Hospital Capical Medical University | Beijing | China | 100015 | |
| 16 | Peking University People's Hospital | Beijing | China | 100044 | |
| 17 | The First Bethune Hospital of Jilin University | Changchun | China | 130021 | |
| 18 | West China Hospital, Sichuan University | Chengdu | China | 610041 | |
| 19 | The Second Affiliated Hospital of Chongqing Medical University | Chongqing | China | 400010 | |
| 20 | Guangzhou Eighth People's Hospital, Guangzhou Medical University | Guangzhou | China | 510000 | |
| 21 | Nanfang Hospital | Guangzhou | China | 510515 | |
| 22 | The First Affiliated Hospital, Zhejiang University College of Medicine | Hangzhou | China | 310003 | |
| 23 | Huashan Hospital Fudan University | Shanghai | China | 200040 | |
| 24 | The First Affiliated Hospital of Xi'an Jiaotong University | Xi'an | China | 710061 | |
| 25 | Hôpital Beaujon | Clichy | France | 92110 | |
| 26 | Hopital de La Croix Rousse | Lyon | France | 69004 | |
| 27 | CHU de Nantes hôtel-Dieu | Nantes | France | 44093 | |
| 28 | CHU Hôpital Saint Antoine | Paris | France | 75012 | |
| 29 | Chu Rennes - Hopital Pontchaillou | Rennes | France | 35033 | |
| 30 | Zentrum für Infektiologie Berlin Prenzlauer Berg GmbH | Berlin | Germany | 10439 | |
| 31 | Universitatsklinikum Essen | Essen | Germany | 45147 | |
| 32 | Universitätsklinikum Johann Wolfgang Goethe- Universität Frankfurt Medizinische Klinik 1 | Frankfurt | Germany | 60590 | |
| 33 | University Medical Center | Hamburg | Germany | D-20246 | |
| 34 | Medizinische Hochschule Hannover | Hannover | Germany | 30625 | |
| 35 | Irccs Ospedale Maggiore Di Milano | Milano | Italy | 20122 | |
| 36 | Azienda Ospedaliero Universitaria Pisana | Pisa | Italy | 56124 | |
| 37 | Universita degli Studi di Roma 'La Sapienza' - Umberto I Policlinico di Roma | Rome | Italy | 00161 | |
| 38 | Ospedale Molinette, AO Città della Salute e della Scienza di | Tourin | Italy | 10126 | |
| 39 | Tokyo Medical and Dental University Hospital | Bunkyo-Ku | Japan | 113-8519 | |
| 40 | Hiroshima Red Cross Hospital & Atomic-bomb Survivors Hospital | Hiroshima | Japan | 730-8619 | |
| 41 | Ikeda City Hospital | Ikeda | Japan | 563-8510 | |
| 42 | Kumamoto University Hospital | Kumamoto | Japan | 860-8556 | |
| 43 | Kumamoto Shinto General Hospital | Kumamoto | Japan | 862-8655 | |
| 44 | Nagasaki University Hospital | Nagasaki | Japan | 852-8501 | |
| 45 | National Hospital Organization Nagasaki Medical Center | Nagasaki | Japan | 856-8562 | |
| 46 | University of the Ryukyus Hospital | Nakagami gun | Japan | 903-0215 | |
| 47 | Nakagami Hospital | Okinawa | Japan | 904-2195 | |
| 48 | Osaka University Hospital | Suita-shi | Japan | 565-0871 | |
| 49 | Suita Municipal Hospital | Suita | Japan | 564-8567 | |
| 50 | New Zealand Clinical Research | Auckland | New Zealand | 1010 | |
| 51 | Irkutsk State Medical University | Irkutsk | Russian Federation | 664003 | |
| 52 | Republic Clinical Infectious Hospital n.a. AF Agafonov | Kazan | Russian Federation | 420140 | |
| 53 | Krasnoyarsk Regional Center For AIDS And Infectious Diseases Treatment And Prophylaxis | Krasnoyarsk | Russian Federation | 660049 | |
| 54 | St. Petersburg City Center for AIDS and Infectious Diseases Treatment and Prophylaxis | Saint Petersburg | Russian Federation | 190103 | |
| 55 | Medical Company Hepatolog Ltd | Samara | Russian Federation | 443045 | |
| 56 | Smolensk Regional Clinical Hospital | Smolensk | Russian Federation | 214018 | |
| 57 | North East Federal University n.a. M.K.Amosov | Yakutsk | Russian Federation | 677000 | |
| 58 | Hosp. Clinic I Provincial de Barcelona | Barcelona | Spain | 8028 | |
| 59 | Hosp. Univ. Vall D Hebron | Barcelona | Spain | 8035 | |
| 60 | Hosp. Univ. 12 de Octubre | Madrid | Spain | 28041 | |
| 61 | Hosp. Univ. Marques de Valdecilla | Santander | Spain | 39008 | |
| 62 | Danderyds Sjukhus | Danderyd | Sweden | 18288 | |
| 63 | Sahlgrenska University Hospital | Göteborg | Sweden | 41685 | |
| 64 | Skanes universitetssjukhus | Malmö | Sweden | 20502 | |
| 65 | Karolinska Universitetssjukhuset Huddinge | Stockholm | Sweden | 14186 | |
| 66 | Kaohsiung Medical University Chung-Ho Memorial Hospital | Kaohsiung | Taiwan | 80756 | |
| 67 | National Taiwan University Hospital | Taipei | Taiwan | 10002 | |
| 68 | China Medical University Hospital | Tiachung | Taiwan | ||
| 69 | Hacettepe University Hospital | Ankara | Turkey | 06230 | |
| 70 | Istanbul University Cerrahpasa Medical Faculty | Istanbul | Turkey | 34098 | |
| 71 | Ege University Medical of Faculty, Department of Gastroenterology | Izmir | Turkey | 35100 | |
| 72 | Kocaeli University Medical Faculty | Kocaeli | Turkey | 41001 | |
| 73 | Acibadem Mehmet Ali Aydinlar University | Kucukcekmece | Turkey | 34303 | |
| 74 | Karadeniz Teknik University Medical Faculty | Trabzon | Turkey | 61080 | |
| 75 | Royal Free London NHS Foundation Trust | London | United Kingdom | NW32QR | |
| 76 | Kings College Hospital | London | United Kingdom | SE5 9RF | |
| 77 | St George's, University of London and St George's University Hospitals NHS Foundation Trust | London | United Kingdom | SW17 0RE |
Sponsors and Collaborators
- Janssen Research & Development, LLC
Investigators
- Study Director: Janssen Research & Development, LLC Clinical Trial, Janssen Research & Development, LLC
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- CR108868
- 2020-001249-37
- 73763989HPB2004