A Trial To Evaluate The Efficacy And Safety Of Multiple Combination Therapies In Participants With Chronic Hepatitis B

Hepatitis B, Chronic Clinical Trial

— Piranga  

Official 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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04225715
• Other study ID #: WV41073
• Secondary ID: 2019-002086-35
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: July 5, 2020
• Est. completion date: January 31, 2025

Study information

• Verified date: April 2024
• Source: Hoffmann-La Roche
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 280
• Est. completion date: January 31, 2025
• Est. primary completion date: August 15, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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.

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.

Related Conditions & MeSH terms

• Hepatitis
• Hepatitis A
• Hepatitis B
• Hepatitis B, Chronic

Intervention

Drug:
• Nucleos(t)ide (NUC)
Nucleos(t)ide (NUC) will be administered orally
• CpAM (RO7049389)
CpAM (RO7049389) will be administered orally
• TLR7 (RO7020531)
TLR7 (RO7020531) will be administered orally
• siRNA (RO7445482)
siRNA (RO7445482) will be administered subcutaneously
• PEG-IFN
PEG-IFN will be administered subcutaneously
• PD-L1 LNA (RO7191863)
PD-L1 LNA (RO7191863) will be administered subcutaneously

Locations

Country	Name	City	State
Bulgaria	Tokuda Hospital Sofia; Hematology department	Sofia
Bulgaria	University Multiprofile Hospital For Active Treatment "Sveti Ivan Rilski" EAD; clinical hematology	Sofia
Bulgaria	Medical Center "Nov Rehabilitatsionen Tsentar", EOOD	Stara Zagora
Canada	University of Calgary; HSC- Faculty of Medicine	Calgary	Alberta
Canada	Uni of Alberta Hospital	Edmonton	Alberta
Canada	Ottawa Hospital	Ottawa	Ontario
Canada	Toronto General Hospital	Toronto	Ontario
Canada	Toronto Liver Centre	Toronto	Ontario
Chile	Hospital San Juan de Dios La Serena	La Serena
China	Beijing Friendship Hospital	Beijing
China	Peking University People's Hospital	Beijing
China	The First Hospital of Jilin University	Changchun City
China	West China Hospital, Sichuan University	Chengdu
China	Nanfang Hospital, Southern Medical University	Guangzhou
China	Capital Medical University (CMU) - Beijing Ditan Hospital; Liver Center (Center for Liver Diseases)	Hangzhou City
China	Huashan Hospital, Fudan University	Shanghai City
China	Ruijin Hospital Shanghai Jiaotong University School of Medicine	Shanghai City
France	Hopital Beaujon; Chir 2	Clichy
France	Hopital de la Croix-Rousse ? Groupement Hospitalier Nord; Pharmacie / Secteur Essais Cliniques	Lyon
France	Hopital Brabois Adultes; Service Médecine Interne Hématologie	Vandoeuvre-les-nancy
Hong Kong	Queen Mary Hospital	Hong Kong
Hong Kong	Prince of Wales Hospital	Shatin, New Territories
Korea, Republic of	Inje University Busan Paik Hospital; Clinical Trial Center	Busan
Korea, Republic of	Pusan National University Hospital	Busan
Korea, Republic of	Chuncheon Sacred Heart Hospital	Gangwon-Do
Korea, Republic of	Asan Medical Center / Clinical Trial Center	Seoul
Korea, Republic of	Seoul National University College of Medicine, Liver Research Institute	Seoul
Korea, Republic of	SMG-SNU Boramae Medical Center	Seoul
Korea, Republic of	Yonsei Uni College of Medicine, Severance Hospital; Internal Medicine Dept.	Seoul
New Zealand	Auckland Clinical Studies Limited	Auckland
New Zealand	Middlemore Clinical Trials	Auckland
Romania	Spitalul Clinic Judetean de Urgenta Cluj Napoca	Cluj-Napoca
Spain	Vall d?Hebron Institute of Oncology (VHIO), Barcelona	Barcelona
Spain	Hospital Universitario Puerta de Hierro	Majadahonda	Madrid
Spain	Hospital Montecelo	Pontevedra
Spain	Hospital Alvaro Cunqueiro; Servicio de Farmacia. Planta -1	Vigo	Pontevedra
Taiwan	Changhua Christian Hospital	Chang Hua
Taiwan	Kaohsiung Medical University Chung-Ho Memorial Hospital; Pharmacy	Kaohsiung City
Taiwan	China Medical University Hospital; Internal Medicine	Taichung
Taiwan	Taichung Veterans General Hospital	Taichung
Taiwan	National Cheng Kung Univ Hosp	Tainan
Taiwan	National Taiwan University Hospital	Taipei
Thailand	Hivnat; Thai Red Cross Center	Bangkok
Thailand	King Chulalongkorn Memorial Hospital	Bangkok
Thailand	Siriraj Hospital	Bangkok
Thailand	Maharaj Nakorn Chiang Mai Hospital	Chiang Mai
United Kingdom	Royal Liverpool University Hospital	Liverpool
United Kingdom	King College Hospital NHS Foundation Trust	London
United Kingdom	St George's Hospital	London
United States	Inland Empire Liver Foundation	Rialto	California
United States	Quest Clinical Research	San Francisco	California

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Countries where clinical trial is conducted

United States,  Bulgaria,  Canada,  Chile,  China,  France,  Hong Kong,  Korea, Republic of,  New Zealand,  Romania,  Spain,  Taiwan,  Thailand,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants with Hepatitis B Surface Antigen (HBsAg) loss at 24 weeks post-EOT (End Of Treatment)		Up to 72 weeks
Secondary	Percentage of Participants with HBsAg loss		Up to 96 weeks
Secondary	Percentage of Participants with HBsAg seroconversion		Up to 96 weeks
Secondary	Percentage of Participants with Hepatitis B Early Antigen (HBeAg) loss (baseline HBeAg-positive participants).		Up to 96 weeks
Secondary	Percentage of Participants with HBeAg seroconversion (baseline HBeAgpositive participants)		Up to 96 weeks
Secondary	Percentage of Participants with HBV DNA < lower limit of quantification (LLOQ), <200 IU/mL and <2,000 IU/mL		Up to 96 weeks
Secondary	Change from baseline in quantitative HBsAg, anti-HBs, HBeAg, anti-HBe, anti-HBc, HBcrAg, HBV RNA, and HBV DNA levels over time (IU/mL)		Up to 96 weeks
Secondary	Plasma Pharmacokinetics (PK) (TLR7) (IU/mL)		Up to 48 weeks
Secondary	Plasma PK (CpAM) (IU/mL)		Up to 48 weeks
Secondary	Plasma PK (NUC) (IU/mL)		Up to 48 weeks
Secondary	Plasma PK (siRNA) (IU/mL)		Up to 48 weeks
Secondary	Serum PK (PEG-IFN) (IU/mL)		Up to 48 weeks
Secondary	Percentage of Participants with Adverse Events (AEs)		Up to 96 weeks
Secondary	Percentage of Participants with Anti-siRNA Antibodies		Up to 96 weeks
Secondary	Percentage of Participants with Anti-PEG-IFN Antibodies		Up to 96 weeks
Secondary	Plasma PK PD-L1 LNA		Up to 37 weeks
Secondary	Percentage of Participants with Anti PD-L1 LNA Antibodies		Up to 85 weeks