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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT04225715




Registration number
NCT04225715
Ethics application status
Date submitted
8/01/2020
Date registered
13/01/2020
Date last updated
11/04/2024

Titles & IDs
Public title
A Trial To Evaluate The Efficacy And Safety Of Multiple Combination Therapies In Participants With Chronic Hepatitis B
Scientific title
A Phase II, Randomised, Adaptive, Open-Label Platform Trial To Evaluate Efficacy And Safety Of Multiple Combination Therapies In Participants With Chronic Hepatitis B
Secondary ID [1] 0 0
2019-002086-35
Secondary ID [2] 0 0
WV41073
Universal Trial Number (UTN)
Trial acronym
Piranga
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Hepatitis B, 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 - Nucleos(t)ide (NUC)
Treatment: Drugs - CpAM (RO7049389)
Treatment: Drugs - TLR7 (RO7020531)
Treatment: Drugs - siRNA (RO7445482)
Treatment: Drugs - PEG-IFN
Treatment: Drugs - PD-L1 LNA (RO7191863)

Active Comparator: Nucleos(t)ide (NUC) Control Arm - Participants will continue their background NUC therapy for the 48-week treatment period. At the end of the treatment period, in line with current CHB treatment guidelines, participants will continue NUC treatment during the follow-up unless the NUC discontinuation criteria have been met.

Experimental: Core Protein Allosteric Modulator (CpAM; RO7049389) + Toll-like Receptor 7 (TLR7;RO7020531) + NUC - Participants will receive RO7049389 (600 mg once daily [QD]) in addition to their background NUC therapy for the 48-week treatment period. RO7020531 (150 mg once every other day [QOD]) will be administered during Weeks 1-12 and Weeks 25-36. At the end of the treatment period, participants will continue NUC treatment during the follow-up unless the NUC discontinuation criteria have been met.

Experimental: Short Interfering Ribonucleic acid (siRNA; RO7445482) (Dose1) + NUC - Participants will receive RO7445482 (Dose 1) in addition to their background NUC therapy for the 48-week treatment period. At the end of the treatment period, participants will continue NUC treatment during the follow-up unless the NUC discontinuation criteria have been met.

Experimental: siRNA (RO7445482) (Dose 2) + NUC - Participants will receive RO7445482 (Dose 2) in addition to their background NUC therapy for the 48-week treatment period. At the end of the treatment period, participants will continue NUC treatment during the follow-up unless the NUC discontinuation criteria have been met.

Experimental: siRNA (RO7445482) + Pegylated Interferon (PEG-IFN) + NUC - Participants will receive RO7445482 (Dose 2) in addition to their background NUC therapy for the 48-week treatment period. PEG-IFN will be administered at a dose of 180 µg once weekly (QW) for 48 weeks. At the end of the treatment period, participants will continue NUC treatment during the follow-up unless the NUC discontinuation criteria have been met.

Experimental: siRNA (RO7445482) + CpAM (RO7049389) + NUC - Participants will receive RO7445482 (Dose 2) and RO7049389 (600 mg QD) in addition to their background NUC therapy for the 48-week treatment period. At the end of the treatment period, participants will continue NUC treatment during the follow-up unless the NUC discontinuation criteria have been met.

Experimental: siRNA (RO7445482) + TLR7 (RO7020531) + NUC - Participants will receive RO7445482 (Dose 2) in addition to their background NUC therapy for the 48-week treatment period. RO7020531 (150 mg QOD) will be administered during Weeks 13-24 and Weeks 37-48 (i.e., 2 treatment cycles of 12 weeks' duration each and 42 doses of RO7020531 for each cycle). At the end of the treatment period, participants will continue NUC treatment during the follow-up unless the NUC discontinuation criteria have been met.

Experimental: siRNA(RO7445482)+ Programmed Death Ligand-1 Locked Nucleic Acid (PD-L1 LNA; RO7191863) + NUC [1] - Participants will receive RO7445482 (Dose 2) during Weeks 1-24 and RO7191863 (Dose 1) will be administered during Weeks 13-24, in addition to their background NUC therapy for the 24-week treatment period. At the end of the treatment period, participants will continue NUC treatment during the follow-up unless the NUC discontinuation criteria have been met.

Experimental: siRNA (RO7445482) + PD-L1 LNA (RO7191863) + NUC [2] - Participants will receive RO7445482 (Dose 2) during Weeks 1-24 and RO7191863 (Dose 1) will be administered during Weeks 25-36, in addition to their background NUC therapy for the 36-week treatment period. At the end of the treatment period, participants will continue NUC treatment during the follow-up unless the NUC discontinuation criteria have been met.


Treatment: Drugs: Nucleos(t)ide (NUC)
Nucleos(t)ide (NUC) will be administered orally

Treatment: Drugs: CpAM (RO7049389)
CpAM (RO7049389) will be administered orally

Treatment: Drugs: TLR7 (RO7020531)
TLR7 (RO7020531) will be administered orally

Treatment: Drugs: siRNA (RO7445482)
siRNA (RO7445482) will be administered subcutaneously

Treatment: Drugs: PEG-IFN
PEG-IFN will be administered subcutaneously

Treatment: Drugs: PD-L1 LNA (RO7191863)
PD-L1 LNA (RO7191863) will be administered subcutaneously
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Percentage of Participants with Hepatitis B Surface Antigen (HBsAg) loss at 24 weeks post-EOT (End Of Treatment)
Timepoint [1] 0 0
Up to 72 weeks
Secondary outcome [1] 0 0
Percentage of Participants with HBsAg loss
Timepoint [1] 0 0
Up to 96 weeks
Secondary outcome [2] 0 0
Percentage of Participants with HBsAg seroconversion
Timepoint [2] 0 0
Up to 96 weeks
Secondary outcome [3] 0 0
Percentage of Participants with Hepatitis B Early Antigen (HBeAg) loss (baseline HBeAg-positive participants).
Timepoint [3] 0 0
Up to 96 weeks
Secondary outcome [4] 0 0
Percentage of Participants with HBeAg seroconversion (baseline HBeAgpositive participants)
Timepoint [4] 0 0
Up to 96 weeks
Secondary outcome [5] 0 0
Percentage of Participants with HBV DNA < lower limit of quantification (LLOQ), <200 IU/mL and <2,000 IU/mL
Timepoint [5] 0 0
Up to 96 weeks
Secondary outcome [6] 0 0
Change from baseline in quantitative HBsAg, anti-HBs, HBeAg, anti-HBe, anti-HBc, HBcrAg, HBV RNA, and HBV DNA levels over time (IU/mL)
Timepoint [6] 0 0
Up to 96 weeks
Secondary outcome [7] 0 0
Plasma Pharmacokinetics (PK) (TLR7) (IU/mL)
Timepoint [7] 0 0
Up to 48 weeks
Secondary outcome [8] 0 0
Plasma PK (CpAM) (IU/mL)
Timepoint [8] 0 0
Up to 48 weeks
Secondary outcome [9] 0 0
Plasma PK (NUC) (IU/mL)
Timepoint [9] 0 0
Up to 48 weeks
Secondary outcome [10] 0 0
Plasma PK (siRNA) (IU/mL)
Timepoint [10] 0 0
Up to 48 weeks
Secondary outcome [11] 0 0
Serum PK (PEG-IFN) (IU/mL)
Timepoint [11] 0 0
Up to 48 weeks
Secondary outcome [12] 0 0
Percentage of Participants with Adverse Events (AEs)
Timepoint [12] 0 0
Up to 96 weeks
Secondary outcome [13] 0 0
Percentage of Participants with Anti-siRNA Antibodies
Timepoint [13] 0 0
Up to 96 weeks
Secondary outcome [14] 0 0
Percentage of Participants with Anti-PEG-IFN Antibodies
Timepoint [14] 0 0
Up to 96 weeks
Secondary outcome [15] 0 0
Plasma PK PD-L1 LNA
Timepoint [15] 0 0
Up to 37 weeks
Secondary outcome [16] 0 0
Percentage of Participants with Anti PD-L1 LNA Antibodies
Timepoint [16] 0 0
Up to 85 weeks

Eligibility
Key inclusion criteria
- Body mass index between 18 and 32 kg/m2 inclusive.

- Participants with Chronic Hepatitis B (CHB) infection (HBsAg positive for >=6 months)
who are on established NUC (entecavir or tenofovir alafenamide/disoproxil fumarate)
monotherapy for >=12 months, having received the same NUC therapy for >=3 months prior
to screening.

- HBV DNA below the lower LLOQ or < 20 IU/mL for > 6 months prior to screening and
confirmed at screening.

- Alanine transaminase (ALT) <=1.5 x upper limit of normal (ULN) for > 6 months prior to
screening and confirmed at screening.

- Female Participants: Eligible to participate if she is not pregnant, not breastfeeding
and agrees to remain abstinent (refrain from heterosexual intercourse) or use highly
effective contraceptive methods.

- Male Participants: During the treatment period and for at least 6 months after the
final dose of study treatment, agrees to remain abstinent (refrain from heterosexual
intercourse), use contraceptive measures and refrain from donating sperm.
Minimum age
18 Years
Maximum age
65 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Pregnant or lactating women.

- Co-infection with other pathogens such as Hepatitis A, C, D and E or Human
Immunodeficiency Virus (HIV).

- History of cirrhosis or current evidence of significant liver fibrosis or cirrhosis or
decompensated liver disease.

- History of or suspicion of Hepatocellular Carcinoma (HCC).

- Thyroid disease poorly controlled on prescribed medications or clinically relevant
abnormal thyroid function tests.

- Clinically significant disease other than CHB that, in the opinion of the
Investigator, makes the participant unsuitable for the study.

- Pre-existing cardiac disease that in the opinion of the investigator would increase
the risk for the participant to take part in the study.

- History of alcohol abuse and/or drug abuse within one year of randomization.

- History of having received (in the last 6 months) or currently receiving any systemic
antineoplastic (including radiation) or immunosuppressive (including biologic
immunosuppressors) or immune modulating treatment.

- Currently taking, or have received within 3 months of Day 1, systemic corticosteroids.

- Electrocardiogram (ECG) with clinically significant abnormalities.

- Previous treatment with an investigational agent for Hepatitis B (HBV) within 6 months
prior to screening.

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
Open (masking not used)
Who is / are masked / blinded?



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
5/07/2020
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
31/01/2025
Actual
Sample size
Target
Accrual to date
Final
280
Recruitment in Australia
Recruitment state(s)
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
Bulgaria
State/province [2] 0 0
Sofia
Country [3] 0 0
Bulgaria
State/province [3] 0 0
Stara Zagora
Country [4] 0 0
Canada
State/province [4] 0 0
Alberta
Country [5] 0 0
Canada
State/province [5] 0 0
Ontario
Country [6] 0 0
Chile
State/province [6] 0 0
La Serena
Country [7] 0 0
China
State/province [7] 0 0
Beijing
Country [8] 0 0
China
State/province [8] 0 0
Changchun City
Country [9] 0 0
China
State/province [9] 0 0
Chengdu
Country [10] 0 0
China
State/province [10] 0 0
Guangzhou
Country [11] 0 0
China
State/province [11] 0 0
Hangzhou City
Country [12] 0 0
China
State/province [12] 0 0
Shanghai City
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
Vandoeuvre-les-nancy
Country [16] 0 0
Hong Kong
State/province [16] 0 0
Hong Kong
Country [17] 0 0
Hong Kong
State/province [17] 0 0
Shatin, New Territories
Country [18] 0 0
Korea, Republic of
State/province [18] 0 0
Busan
Country [19] 0 0
Korea, Republic of
State/province [19] 0 0
Gangwon-Do
Country [20] 0 0
Korea, Republic of
State/province [20] 0 0
Seoul
Country [21] 0 0
New Zealand
State/province [21] 0 0
Auckland
Country [22] 0 0
Romania
State/province [22] 0 0
Cluj-Napoca
Country [23] 0 0
Spain
State/province [23] 0 0
Madrid
Country [24] 0 0
Spain
State/province [24] 0 0
Pontevedra
Country [25] 0 0
Spain
State/province [25] 0 0
Barcelona
Country [26] 0 0
Taiwan
State/province [26] 0 0
Chang Hua
Country [27] 0 0
Taiwan
State/province [27] 0 0
Kaohsiung City
Country [28] 0 0
Taiwan
State/province [28] 0 0
Taichung
Country [29] 0 0
Taiwan
State/province [29] 0 0
Tainan
Country [30] 0 0
Taiwan
State/province [30] 0 0
Taipei
Country [31] 0 0
Thailand
State/province [31] 0 0
Bangkok
Country [32] 0 0
Thailand
State/province [32] 0 0
Chiang Mai
Country [33] 0 0
United Kingdom
State/province [33] 0 0
Liverpool
Country [34] 0 0
United Kingdom
State/province [34] 0 0
London

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Hoffmann-La Roche
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
This is a study designed to evaluate the safety, tolerability and efficacy of New Molecular
Entity (NME) combination therapies in Chronic Hepatitis B (CHB) participants with preserved
liver function and without significant fibrosis/cirrhosis. The platform design allows
comparison of multiple NME combination therapies against a common control, and introduction
of additional treatment arms at later study time points. Each arm will consist of a screening
phase (up to 8 weeks), treatment phase (up to 48 weeks) and post-treatment follow-up phase
(48 weeks). The safety and efficacy will be monitored throughout the study.
Trial website
https://clinicaltrials.gov/ct2/show/NCT04225715
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Clinical Trials
Address 0 0
Hoffmann-La Roche
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