Trial Review

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/ct2/show/NCT04535544




Registration number
NCT04535544
Ethics application status
Date submitted
28/08/2020
Date registered
2/09/2020
Date last updated
22/05/2024

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
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/ct2/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
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT04535544