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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT04535544




Registration number
NCT04535544
Ethics application status
Date submitted
28/08/2020
Date registered
2/09/2020
Date last updated
14/04/2021

Titles & IDs
Public title
A Study of JNJ-73763989 + Nucleos(t)Ide Analog in Participants Co-Infected With Hepatitis B and Hepatitis D Virus
Scientific 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
Secondary ID [1] 0 0
2020-001249-37
Secondary ID [2] 0 0
CR108868
Universal Trial Number (UTN)
Trial acronym
REEF-D
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Hepatitis D, Chronic 0 0
Condition category
Condition code
Infection 0 0 0 0
Other infectious diseases
Oral and Gastrointestinal 0 0 0 0
Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - JNJ-73763989
Treatment: Drugs - Placebo
Treatment: Drugs - Entecavir (ETV) monohydrate
Treatment: Drugs - Tenofovir disoproxil
Treatment: Drugs - Tenofovir alafenamide (TAF)

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.

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.


Treatment: Drugs: JNJ-73763989
JNJ-73763989 will be administered as a SC injection.

Treatment: Drugs: Placebo
Matching placebo to JNJ-73763989 will be administered as a SC injection.

Treatment: Drugs: Entecavir (ETV) monohydrate
ETV monohydrate film coated tablet will be administered orally.

Treatment: Drugs: Tenofovir disoproxil
Tenofovir disoproxil film-coated tablet will be administered orally.

Treatment: Drugs: Tenofovir alafenamide (TAF)
TAF film coated tablet will be administered orally.

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
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.
Timepoint [1] 0 0
Week 48
Secondary outcome [1] 0 0
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.
Timepoint [1] 0 0
Week 48
Secondary outcome [2] 0 0
Percentage of Participants With Normal ALT at Week 48 - Percentage of participants with normal ALT at Week 48 will be reported.
Timepoint [2] 0 0
Week 48
Secondary outcome [3] 0 0
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.
Timepoint [3] 0 0
Week 48
Secondary outcome [4] 0 0
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.
Timepoint [4] 0 0
Week 48
Secondary outcome [5] 0 0
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.
Timepoint [5] 0 0
Up to Week 204
Secondary outcome [6] 0 0
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.
Timepoint [6] 0 0
Up to Week 204
Secondary outcome [7] 0 0
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.
Timepoint [7] 0 0
Up to Week 204
Secondary outcome [8] 0 0
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.
Timepoint [8] 0 0
Up to Week 204
Secondary outcome [9] 0 0
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.
Timepoint [9] 0 0
Up to Week 204
Secondary outcome [10] 0 0
Percentage of Participants with HDV RNA TND - Percentage of participants with HDV RNA TND will be reported.
Timepoint [10] 0 0
Up to Week 204
Secondary outcome [11] 0 0
Percentage of Participants with Normal ALT - Percentage of participants with normal ALT will be reported.
Timepoint [11] 0 0
Up to Week 204
Secondary outcome [12] 0 0
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.
Timepoint [12] 0 0
Up to Week 204
Secondary outcome [13] 0 0
Change from Baseline in HDV RNA - Change from baseline in HDV RNA will be reported.
Timepoint [13] 0 0
Baseline and up to Week 204
Secondary outcome [14] 0 0
Changes from Baseline in ALT - Changes from baseline in ALT will be reported.
Timepoint [14] 0 0
Baseline and up to Week 204
Secondary outcome [15] 0 0
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.
Timepoint [15] 0 0
Up to Week 204
Secondary outcome [16] 0 0
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.
Timepoint [16] 0 0
Up to Week 204
Secondary outcome [17] 0 0
Percentage of Participants with Abnormalities in 12-lead Electrocardiogram (ECGs) - Percentage of participants with abnormalities in 12-lead electrocardiogram (ECGs) will be reported.
Timepoint [17] 0 0
Up to Week 204
Secondary outcome [18] 0 0
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.
Timepoint [18] 0 0
Up to Week 204
Secondary outcome [19] 0 0
Percentage of Participants with Abnormalities in Physical Examination - Percentage of participants with abnormalities in physical examination will be reported.
Timepoint [19] 0 0
Up to Week 204
Secondary outcome [20] 0 0
Percentage of Participants with HBsAg Seroclearance and/or Seroconversion - Percentage of participants with HBsAg seroclearance and/or seroconversion will be reported.
Timepoint [20] 0 0
Up to Week 204
Secondary outcome [21] 0 0
Change from Baseline Over Time in HBsAg - Change from baseline over time in HBsAg will be reported.
Timepoint [21] 0 0
Baseline and up to Week 204
Secondary outcome [22] 0 0
Change from Baseline Over Time in HBeAg - Change from baseline over time in HBeAg will be reported.
Timepoint [22] 0 0
Baseline and up to Week 204
Secondary outcome [23] 0 0
Change from Baseline Over Time in HBV DNA - Change from baseline over time in HBV DNA will be reported.
Timepoint [23] 0 0
Baseline and up to Week 204
Secondary outcome [24] 0 0
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.
Timepoint [24] 0 0
Up to Week 204
Secondary outcome [25] 0 0
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.
Timepoint [25] 0 0
Up to Week 204
Secondary outcome [26] 0 0
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.
Timepoint [26] 0 0
Up to Week 204
Secondary outcome [27] 0 0
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.
Timepoint [27] 0 0
Baseline and up to Week 204
Secondary outcome [28] 0 0
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.
Timepoint [28] 0 0
Baseline and up to Week 204
Secondary outcome [29] 0 0
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.
Timepoint [29] 0 0
Baseline and up to Week 204
Secondary outcome [30] 0 0
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.
Timepoint [30] 0 0
Up to Week 204
Secondary outcome [31] 0 0
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.
Timepoint [31] 0 0
Up to Week 204
Secondary outcome [32] 0 0
Area Under the Plasma Concentration-time Curve (AUC) of JNJ-73763989 and Optionally NA - Area under the plasma concentration-time curve (AUC) of JNJ-73763989 and optionally NA will be reported.
Timepoint [32] 0 0
Up to Week 124
Secondary outcome [33] 0 0
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.
Timepoint [33] 0 0
Up to Week 204
Secondary outcome [34] 0 0
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.
Timepoint [34] 0 0
Baseline and up to Week 204
Secondary outcome [35] 0 0
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.
Timepoint [35] 0 0
Up to Week 204
Secondary outcome [36] 0 0
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.
Timepoint [36] 0 0
Up to Week 204
Secondary outcome [37] 0 0
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.
Timepoint [37] 0 0
Up to Week 204
Secondary outcome [38] 0 0
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.
Timepoint [38] 0 0
Up to Week 204
Secondary outcome [39] 0 0
Change from Baseline in Hepatitis B Quality of Life (HBQOL) Scale And Subscales - 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).
Timepoint [39] 0 0
Baseline and up to Week 204

Eligibility
Key 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

- Hepatitis D RNA (HDV RNA) greater than (>) 1000 international units per milliliter
(IU/mL) at screening

- 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
Minimum age
18 Years
Maximum age
65 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key 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 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)

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Eastern Health Research - Box Hill
Recruitment hospital [2] 0 0
Royal Prince Alfred Hospital - Camperdown
Recruitment hospital [3] 0 0
Westmead Hospital - Westmead
Recruitment postcode(s) [1] 0 0
3128 - Box Hill
Recruitment postcode(s) [2] 0 0
2050 - Camperdown
Recruitment postcode(s) [3] 0 0
2145 - Westmead
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Maryland
Country [3] 0 0
United States of America
State/province [3] 0 0
Massachusetts
Country [4] 0 0
United States of America
State/province [4] 0 0
New Jersey
Country [5] 0 0
Brazil
State/province [5] 0 0
Boa Vista
Country [6] 0 0
Brazil
State/province [6] 0 0
Manaus
Country [7] 0 0
Brazil
State/province [7] 0 0
Porto Velho
Country [8] 0 0
China
State/province [8] 0 0
Beijing
Country [9] 0 0
China
State/province [9] 0 0
Changchun
Country [10] 0 0
China
State/province [10] 0 0
Chengdu
Country [11] 0 0
China
State/province [11] 0 0
Chongqing
Country [12] 0 0
China
State/province [12] 0 0
Guangzhou
Country [13] 0 0
China
State/province [13] 0 0
Hangzhou
Country [14] 0 0
China
State/province [14] 0 0
Shanghai
Country [15] 0 0
France
State/province [15] 0 0
Clichy
Country [16] 0 0
France
State/province [16] 0 0
Nantes
Country [17] 0 0
France
State/province [17] 0 0
Paris
Country [18] 0 0
Germany
State/province [18] 0 0
Berlin
Country [19] 0 0
Germany
State/province [19] 0 0
Essen
Country [20] 0 0
Germany
State/province [20] 0 0
Frankfurt
Country [21] 0 0
Germany
State/province [21] 0 0
Hannover
Country [22] 0 0
Italy
State/province [22] 0 0
Milano
Country [23] 0 0
Italy
State/province [23] 0 0
Pisa
Country [24] 0 0
Italy
State/province [24] 0 0
Rome
Country [25] 0 0
Italy
State/province [25] 0 0
Tourin
Country [26] 0 0
Japan
State/province [26] 0 0
Bunkyo-ku
Country [27] 0 0
Japan
State/province [27] 0 0
Kumamoto
Country [28] 0 0
Japan
State/province [28] 0 0
Nagasaki
Country [29] 0 0
Japan
State/province [29] 0 0
Nakagami gun
Country [30] 0 0
Japan
State/province [30] 0 0
Suita
Country [31] 0 0
New Zealand
State/province [31] 0 0
Auckland
Country [32] 0 0
Russian Federation
State/province [32] 0 0
Irkutsk
Country [33] 0 0
Russian Federation
State/province [33] 0 0
Krasnoyarsk
Country [34] 0 0
Russian Federation
State/province [34] 0 0
Saint Petersburg
Country [35] 0 0
Russian Federation
State/province [35] 0 0
Samara
Country [36] 0 0
Russian Federation
State/province [36] 0 0
Smolensk
Country [37] 0 0
Russian Federation
State/province [37] 0 0
Yakutsk
Country [38] 0 0
Spain
State/province [38] 0 0
Barcelona
Country [39] 0 0
Spain
State/province [39] 0 0
Madrid
Country [40] 0 0
Spain
State/province [40] 0 0
Santander
Country [41] 0 0
Sweden
State/province [41] 0 0
Danderyd
Country [42] 0 0
Sweden
State/province [42] 0 0
Malmö
Country [43] 0 0
Sweden
State/province [43] 0 0
Stockholm
Country [44] 0 0
Taiwan
State/province [44] 0 0
Kaohsiung
Country [45] 0 0
Taiwan
State/province [45] 0 0
Taipei
Country [46] 0 0
Taiwan
State/province [46] 0 0
Tiachung
Country [47] 0 0
Turkey
State/province [47] 0 0
Ankara
Country [48] 0 0
Turkey
State/province [48] 0 0
Istanbul
Country [49] 0 0
Turkey
State/province [49] 0 0
Izmir
Country [50] 0 0
Turkey
State/province [50] 0 0
Kocaeli
Country [51] 0 0
Turkey
State/province [51] 0 0
Kucukcekmece
Country [52] 0 0
Turkey
State/province [52] 0 0
Trabzon
Country [53] 0 0
United Kingdom
State/province [53] 0 0
London

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Janssen Research & Development, LLC
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/show/NCT04535544
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Janssen Research & Development, LLC Clinical Trial
Address 0 0
Janssen Research & Development, LLC
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Study Contact
Address 0 0
Country 0 0
Phone 0 0
844-434-4210
Fax 0 0
Email 0 0
JNJ.CT@sylogent.com
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT04535544