Register a trial

The ANZCTR website will be unavailable from 1pm until 3pm (AEDT) on Wednesday the 30th of October for website maintenance. Please be sure to log out of the system in order to avoid any loss of data.

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 endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial details imported from ClinicalTrials.gov

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




Registration number
NCT04535544
Ethics application status
Date submitted
28/08/2020
Date registered
2/09/2020

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 for at least 96 weeks in Part 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 for at least 48 weeks in Part 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
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
Timepoint [1] 0 0
Week 48
Secondary outcome [2] 0 0
Percentage of Participants With Normal ALT at Week 48
Timepoint [2] 0 0
Week 48
Secondary outcome [3] 0 0
Percentage of Participants with HBsAg Seroclearance at Week 48
Timepoint [3] 0 0
Week 48
Secondary outcome [4] 0 0
Percentage of Participants with >=2 kPa Reduction From Baseline in LSM assessed by VCTE (FibroScan) at Week 48
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
Timepoint [5] 0 0
Baseline up to Week 196
Secondary outcome [6] 0 0
Percentage of Participants with HDV RNA >=2 log10 IU/mL Decline From Baseline in Combination with Normal ALT
Timepoint [6] 0 0
Up to Week 196
Secondary outcome [7] 0 0
Percentage of Participants with HDV RNA TND in Combination with Normal ALT
Timepoint [7] 0 0
Up to Week 196
Secondary outcome [8] 0 0
Percentage of Participants with HDV RNA >=2 log10 IU/mL Decline From Baseline or HDV RNA TND
Timepoint [8] 0 0
Up to Week 196
Secondary outcome [9] 0 0
Percentage of Participants with HDV RNA >=2 log10 IU/mL Decline From Baseline
Timepoint [9] 0 0
Up to Week 196
Secondary outcome [10] 0 0
Percentage of Participants with HDV RNA TND
Timepoint [10] 0 0
Up to Week 196
Secondary outcome [11] 0 0
Percentage of Participants with Normal ALT
Timepoint [11] 0 0
Up to Week 196
Secondary outcome [12] 0 0
Time to Reach HDV RNA >=2 log10 IU/mL Decline or HDV RNA TND
Timepoint [12] 0 0
Up to Week 196
Secondary outcome [13] 0 0
Change from Baseline in HDV RNA
Timepoint [13] 0 0
Baseline and up to Week 196
Secondary outcome [14] 0 0
Changes from Baseline in ALT
Timepoint [14] 0 0
Baseline and up to Week 196
Secondary outcome [15] 0 0
Percentage of Participants with Adverse Events (AEs) and Serious AEs
Timepoint [15] 0 0
From screening up to Week 196
Secondary outcome [16] 0 0
Percentage of Participants with Abnormalities in Laboratory Parameters
Timepoint [16] 0 0
From screening up to Week 196
Secondary outcome [17] 0 0
Percentage of Participants with Abnormalities in 12-lead Electrocardiogram (ECGs)
Timepoint [17] 0 0
From screening up to Week 196
Secondary outcome [18] 0 0
Percentage of Participants with Abnormalities in Vital Signs
Timepoint [18] 0 0
From screening up to Week 196
Secondary outcome [19] 0 0
Percentage of Participants with Abnormalities in Physical Examination
Timepoint [19] 0 0
From screening up to Week 196
Secondary outcome [20] 0 0
Percentage of Participants with HBsAg Seroclearance and/or Seroconversion
Timepoint [20] 0 0
Up to Week 196
Secondary outcome [21] 0 0
Change from Baseline Over Time in HBsAg
Timepoint [21] 0 0
Baseline and up to Week 196
Secondary outcome [22] 0 0
Change from Baseline Over Time in HBeAg
Timepoint [22] 0 0
Baseline and up to Week 196
Secondary outcome [23] 0 0
Change from Baseline Over Time in HBV DNA
Timepoint [23] 0 0
Baseline and up to Week 196
Secondary outcome [24] 0 0
Percentage of Participants with HBsAg levels below/above different cut-offs
Timepoint [24] 0 0
Up to Week 196
Secondary outcome [25] 0 0
Percentage of Participants with HBeAg levels below/above different cut-offs
Timepoint [25] 0 0
Up to Week 196
Secondary outcome [26] 0 0
Percentage of Participants with HBV DNA levels below/above different cut-offs
Timepoint [26] 0 0
Up to Week 196
Secondary outcome [27] 0 0
Percentage of Participants with HBsAg Change From Baseline Below/Above Different Cut-offs
Timepoint [27] 0 0
Baseline and up to Week 196
Secondary outcome [28] 0 0
Percentage of Participants with HBeAg Change From Baseline Below/Above Different Cut-offs
Timepoint [28] 0 0
Baseline and up to Week 196
Secondary outcome [29] 0 0
Percentage of Participants with HBV DNA Change From Baseline Below/Above Different Cut-offs
Timepoint [29] 0 0
Baseline and up to Week 196
Secondary outcome [30] 0 0
Time to Reach Efficacy Thresholds such as HBsAg <1 IU/mL
Timepoint [30] 0 0
Up to Week 196
Secondary outcome [31] 0 0
Percentage of Participants with HBV DNA Virologic Breakthrough
Timepoint [31] 0 0
Up to Week 196
Secondary outcome [32] 0 0
Percentage of Participants with >=2 kPa Reduction from Baseline in LSM Assessed by VCTE (FibroScan)
Timepoint [32] 0 0
Up to Week 196
Secondary outcome [33] 0 0
Change from Baseline in LSM Over Time Assessed by VCTE (FibroScan)
Timepoint [33] 0 0
Baseline and up to Week 196
Secondary outcome [34] 0 0
Percentage of Participants with Sustained HDV Response Off-treatment Post end of JNJ-73763989 Treatment
Timepoint [34] 0 0
Up to Week 196
Secondary outcome [35] 0 0
Percentage of Participants with HDV Relapse Post End of JNJ 73763989 Treatment
Timepoint [35] 0 0
Up to Week 196
Secondary outcome [36] 0 0
Percentage of Participants with Sustained HBV Response Off-Treatment Post End of JNJ-73763989 Treatment.
Timepoint [36] 0 0
Up to Week 196
Secondary outcome [37] 0 0
Percentage of Participants with HBV Flare (Virologic, Biochemical, and Clinical) Post End of Treatment
Timepoint [37] 0 0
Up to Week 196

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
* 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
Minimum age
18 Years
Maximum age
65 Years
Sex
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, 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
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
17/09/2020
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
5/02/2025
Actual
Sample size
Target
Accrual to date
Final
52
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Royal Prince Alfred Hospital - Camperdown
Recruitment hospital [2] 0 0
Western Health - Footscray
Recruitment hospital [3] 0 0
Westmead Hospital - Westmead
Recruitment postcode(s) [1] 0 0
2050 - Camperdown
Recruitment postcode(s) [2] 0 0
3011 - Footscray
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
Massachusetts
Country [3] 0 0
Brazil
State/province [3] 0 0
Boa Vista
Country [4] 0 0
Brazil
State/province [4] 0 0
Manaus
Country [5] 0 0
Brazil
State/province [5] 0 0
Porto Velho
Country [6] 0 0
China
State/province [6] 0 0
Beijing
Country [7] 0 0
China
State/province [7] 0 0
Changchun
Country [8] 0 0
China
State/province [8] 0 0
Chengdu
Country [9] 0 0
China
State/province [9] 0 0
Chongqing
Country [10] 0 0
China
State/province [10] 0 0
Guangzhou
Country [11] 0 0
China
State/province [11] 0 0
Hangzhou
Country [12] 0 0
China
State/province [12] 0 0
Shanghai
Country [13] 0 0
France
State/province [13] 0 0
Clichy
Country [14] 0 0
France
State/province [14] 0 0
Lyon
Country [15] 0 0
France
State/province [15] 0 0
Nantes
Country [16] 0 0
France
State/province [16] 0 0
Paris
Country [17] 0 0
France
State/province [17] 0 0
Rennes
Country [18] 0 0
Germany
State/province [18] 0 0
Essen
Country [19] 0 0
Germany
State/province [19] 0 0
Frankfurt
Country [20] 0 0
Germany
State/province [20] 0 0
Hannover
Country [21] 0 0
Italy
State/province [21] 0 0
Milano
Country [22] 0 0
Italy
State/province [22] 0 0
Pisa
Country [23] 0 0
Italy
State/province [23] 0 0
Rome
Country [24] 0 0
Italy
State/province [24] 0 0
Torino
Country [25] 0 0
Japan
State/province [25] 0 0
Bunkyo Ku
Country [26] 0 0
Japan
State/province [26] 0 0
Hiroshima
Country [27] 0 0
Japan
State/province [27] 0 0
Iizuka-shi
Country [28] 0 0
Japan
State/province [28] 0 0
Ikeda
Country [29] 0 0
Japan
State/province [29] 0 0
Kumamoto
Country [30] 0 0
Japan
State/province [30] 0 0
Nagasaki
Country [31] 0 0
Japan
State/province [31] 0 0
Nakagami gun
Country [32] 0 0
Japan
State/province [32] 0 0
Okinawa
Country [33] 0 0
Japan
State/province [33] 0 0
Suita-shi
Country [34] 0 0
Japan
State/province [34] 0 0
Suita
Country [35] 0 0
Japan
State/province [35] 0 0
Sumida ku
Country [36] 0 0
New Zealand
State/province [36] 0 0
Auckland
Country [37] 0 0
Russian Federation
State/province [37] 0 0
Krasnoyarsk
Country [38] 0 0
Russian Federation
State/province [38] 0 0
Saint Petersburg
Country [39] 0 0
Russian Federation
State/province [39] 0 0
Samara
Country [40] 0 0
Spain
State/province [40] 0 0
Barcelona
Country [41] 0 0
Spain
State/province [41] 0 0
Madrid
Country [42] 0 0
Spain
State/province [42] 0 0
Santander
Country [43] 0 0
Sweden
State/province [43] 0 0
Danderyd
Country [44] 0 0
Sweden
State/province [44] 0 0
Malmö
Country [45] 0 0
Sweden
State/province [45] 0 0
Stockholm
Country [46] 0 0
Taiwan
State/province [46] 0 0
Kaohsiung
Country [47] 0 0
Taiwan
State/province [47] 0 0
Taipei
Country [48] 0 0
Taiwan
State/province [48] 0 0
Tiachung
Country [49] 0 0
Turkey
State/province [49] 0 0
Istanbul
Country [50] 0 0
Turkey
State/province [50] 0 0
Izmir
Country [51] 0 0
Turkey
State/province [51] 0 0
Kocaeli
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
Trial website
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
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
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
When will data be available (start and end dates)?
Available to whom?
Available for what types of analyses?
How or where can data be obtained?
IPD available at link: https://www.janssen.com/clinical-trials/transparency


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results not provided in https://clinicaltrials.gov/study/NCT04535544