Clinical trial NCT04225715: A Trial To Evaluate The Efficacy And Safety Of Multiple Combination Therapies In Participants With Chronic Hepatitis B
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Hepatitis B, Chronic
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2020-01-13
Enrollment: 281
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Percentage of Participants with Hepatitis B Surface Antigen (HBsAg) loss at 24 weeks post-EOT (End Of Treatment)
timeFrame: Up to 72 weeks
Secondary outcomes:
measure: Percentage of Participants with HBsAg loss
timeFrame: Up to 96 weeks
measure: Percentage of Participants with HBsAg seroconversion
timeFrame: Up to 96 weeks
measure: Percentage of Participants with Hepatitis B Early Antigen (HBeAg) loss (baseline HBeAg-positive participants).
timeFrame: Up to 96 weeks
measure: Percentage of Participants with HBeAg seroconversion (baseline HBeAgpositive participants)
timeFrame: Up to 96 weeks
measure: Percentage of Participants with HBV DNA < lower limit of quantification (LLOQ), <200 IU/mL and <2,000 IU/mL
timeFrame: Up to 96 weeks
measure: Change from baseline in quantitative HBsAg, anti-HBs, HBeAg, anti-HBe, anti-HBc, HBcrAg, HBV RNA, and HBV DNA levels over time (IU/mL)
timeFrame: Up to 96 weeks
measure: Plasma Pharmacokinetics (PK) (TLR7) (IU/mL)
timeFrame: Up to 48 weeks
measure: Plasma PK (CpAM) (IU/mL)
timeFrame: Up to 48 weeks
measure: Plasma PK (NUC) (IU/mL)
timeFrame: Up to 48 weeks
measure: Plasma PK (siRNA) (IU/mL)
timeFrame: Up to 48 weeks
measure: Serum PK (PEG-IFN) (IU/mL)
timeFrame: Up to 48 weeks
measure: Percentage of Participants with Adverse Events (AEs)
timeFrame: Up to 96 weeks
measure: Percentage of Participants with Anti-siRNA Antibodies
timeFrame: Up to 96 weeks
measure: Percentage of Participants with Anti-PEG-IFN Antibodies
timeFrame: Up to 96 weeks
measure: Plasma PK PD-L1 LNA
timeFrame: Up to 37 weeks
measure: Percentage of Participants with Anti PD-L1 LNA Antibodies
timeFrame: Up to 85 weeks
Other outcomes:
Locations:
city: Rialto
country: United States
facility: Inland Empire Liver Foundation
state: California
city: San Francisco
country: United States
facility: Quest Clinical Research
state: California
city: Sofia
country: Bulgaria
facility: Tokuda Hospital Sofia; Hematology department
city: Sofia
country: Bulgaria
facility: University Multiprofile Hospital For Active Treatment "Sveti Ivan Rilski" EAD; clinical hematology
city: Stara Zagora
country: Bulgaria
facility: Medical Center "Nov Rehabilitatsionen Tsentar", EOOD
city: Calgary
country: Canada
facility: University of Calgary; HSC- Faculty of Medicine
state: Alberta
city: Edmonton
country: Canada
facility: Uni of Alberta Hospital
state: Alberta
city: Ottawa
country: Canada
facility: Ottawa Hospital
state: Ontario
city: Toronto
country: Canada
facility: Toronto General Hospital
state: Ontario
city: Toronto
country: Canada
facility: Toronto Liver Centre
state: Ontario
city: La Serena
country: Chile
facility: Hospital San Juan de Dios La Serena
city: Beijing
country: China
facility: Peking University People's Hospital
city: Beijing
country: China
facility: Beijing Friendship Hospital
city: Changchun City
country: China
facility: The First Hospital of Jilin University
city: Chengdu
country: China
facility: West China Hospital, Sichuan University
city: Guangzhou
country: China
facility: Nanfang Hospital, Southern Medical University
city: Hangzhou City
country: China
facility: Capital Medical University (CMU) - Beijing Ditan Hospital; Liver Center (Center for Liver Diseases)
city: Shanghai City
country: China
facility: Ruijin Hospital Shanghai Jiaotong University School of Medicine
city: Shanghai City
country: China
facility: Huashan Hospital, Fudan University
city: Clichy
country: France
facility: Hopital Beaujon; Chir 2
city: Lyon
country: France
facility: Hopital de la Croix-Rousse ? Groupement Hospitalier Nord; Pharmacie / Secteur Essais Cliniques
city: Vandoeuvre-les-nancy
country: France
facility: Hopital Brabois Adultes; Service Médecine Interne Hématologie
city: Hong Kong
country: Hong Kong
facility: Queen Mary Hospital
city: Shatin, New Territories
country: Hong Kong
facility: Prince of Wales Hospital
city: Busan
country: Korea, Republic of
facility: Pusan National University Hospital
city: Busan
country: Korea, Republic of
facility: Inje University Busan Paik Hospital; Clinical Trial Center
city: Gangwon-Do
country: Korea, Republic of
facility: Chuncheon Sacred Heart Hospital
city: Seoul
country: Korea, Republic of
facility: Yonsei Uni College of Medicine, Severance Hospital; Internal Medicine Dept.
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center / Clinical Trial Center
city: Seoul
country: Korea, Republic of
facility: SMG-SNU Boramae Medical Center
city: Seoul
country: Korea, Republic of
facility: Seoul National University College of Medicine, Liver Research Institute
city: Auckland
country: New Zealand
facility: Auckland Clinical Studies Limited
city: Auckland
country: New Zealand
facility: Middlemore Clinical Trials
city: Cluj-Napoca
country: Romania
facility: Spitalul Clinic Judetean de Urgenta Cluj Napoca
city: Majadahonda
country: Spain
facility: Hospital Universitario Puerta de Hierro
state: Madrid
city: Vigo
country: Spain
facility: Hospital Alvaro Cunqueiro; Servicio de Farmacia. Planta -1
state: Pontevedra
city: Barcelona
country: Spain
facility: Vall d?Hebron Institute of Oncology (VHIO), Barcelona
city: Pontevedra
country: Spain
facility: Hospital Montecelo
city: Chang Hua
country: Taiwan
facility: Changhua Christian Hospital
city: Kaohsiung City
country: Taiwan
facility: Kaohsiung Medical University Chung-Ho Memorial Hospital; Pharmacy
city: Taichung
country: Taiwan
facility: China Medical University Hospital; Internal Medicine
city: Taichung
country: Taiwan
facility: Taichung Veterans General Hospital
city: Tainan
country: Taiwan
facility: National Cheng Kung Univ Hosp
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital
city: Bangkok
country: Thailand
facility: Hivnat; Thai Red Cross Center
city: Bangkok
country: Thailand
facility: King Chulalongkorn Memorial Hospital
city: Bangkok
country: Thailand
facility: Siriraj Hospital
city: Chiang Mai
country: Thailand
facility: Maharaj Nakorn Chiang Mai Hospital
city: Liverpool
country: United Kingdom
facility: Royal Liverpool University Hospital
city: London
country: United Kingdom
facility: King College Hospital NHS Foundation Trust
city: London
country: United Kingdom
facility: St George's Hospital
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References: