Chronic Hepatitis B (CHB) MedDRA version: 20.1 Level: PT Classification code 10008910 Term: Chronic hepatitis B System Organ Class: 10021881 - Infections and infestations
Conditions
Interventions
Product Name: RO7020531
Product Code: RO7020531/F07
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: n.a.
CAS Number: 1948241-60-8
Current Sponsor code: RO7020531
Other descriptive name: R
Sponsors
F. Hoffmann-La Roche Ltd
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Participant must be 18 to 65 years of age - Body mass index between 18 and 32 kg/m2 inclusive - Participants with CHB infection (HBsAg [Hepatitis B surface antigen] positive for >= 6 months) who are on established Nucleos[t]ide (NUC) monotherapy for >=12 months, having received the same NUC therapy for >=3 months prior to screening - Hepatitis B virus (HBV) Deoxyribonucleic acid (DNA) below the limit of quantification (LLOQ) or 6 months prior to screening and confirmed at screening - Alanine transaminase (ALT) 6 months prior to screening, and confirmed at screening - Screening laboratory values within normal range, or judged not clinically significant by the Investigator and Medical Monitor - Female Participants: Women of non-childbearing potential or women of childbearing potential who agree to remain abstinent or use highly effective contraceptive methods that result in a failure rate of =65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: - Pregnant or lactating women - Co-infection with pathogens such as hepatitis A (HAV), hepatitis C (HCV), hepatitis D (HDV), hepatitis E (HEV), or human immunodeficiency virus (HIV) - History of cirrhosis or current evidence of significant liver fibrosis or cirrhosis, or decompensated liver disease (e.g., ascites, hepatic encephalopathy). Liver biopsy or transient/ Acoustic radiation force impulse/ magnetic resonance elastography result must be obtained within 6 months prior to randomisation - History of or suspicion of Hepatocellular carcinoma - Thyroid disease poorly controlled on prescribed medications or clinically relevant abnormal thyroid function tests at screening, as judged by the Investigator and Medical Monitor - 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 or immunosuppressive or immune modulating treatment for malignant or non-malignant disorders. - Currently taking, or have received within 3 months of Day 1, systemic corticosteroids at a high-dose (e.g., 40 mg prednisolone per day for) > 7 days, or a low-dose (e.g., 20 mg prednisolone per day) for > 14 days. - Electrocardiogram with clinically significant abnormalities - Laboratory parameters at screening •Hemoglobin 1.1 •Albumin ULN (exception: Gilbert's disease). •Positive results for anti-mitochondrial antibodies (AMA > 1:80), antinuclear antibody (ANA > 1:80), anti–smooth muscle antibody (ASMA > 1:40), or anti-thyroperoxidase antibodies (a-TPO > 10) •White blood cell count < 2500 cells/mm3; neutrophil count < 1500 cells/mm3 •Glomerular filtration rate < 60 mL/min •Positive test for drugs of abuse and/or positive alcohol test at screening. For positive cannabinoids test, the eligibility is at the Investigator's discretion. - Previous treatment with an investigational agent for HBV within 6 months prior to screening - Unable to comply with any drugs or nutrients listed in prohibited medications and prohibited food sections in the respective treatment arm appendix.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: • To estimate the effect of new molecular entity (NME) combination therapies on inducing a functional cure over the control arm;Secondary Objective: • To characterize the efficacy profile of NME combination therapies • To characterize the Pharmacodynamic (PD) profile of NME combination therapies • To characterize the plasma Pharmacokinetic (PK) profiles of NMEs • To assess the safety and tolerability of NME combination therapies • To identify presence of PK/PD relationship •To explore potential effects of anti drug antibodies (ADA) on NMEs and/or IMP, as applicable.;Primary end point(s): 1. Percentage of participants with HBsAg loss at 24 weeks post-end of treatment (EOT);Timepoint(s) of evaluation of this end point: 1. At 24 weeks post-EOT | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1.Percentage of participants with HBsAg loss over time 2.Percentage of participants with HBsAg seroconversion over time 3.Percentage of participants with HBeAg (Hepatitis Be antigen) loss (baseline HBeAg-positive participants) over time 4.Percentage of participants with HBeAg seroconversion (baseline HBeAg-positive participants) over time 5.Percentage of participants with HBV DNA < LLOQ, = 200 IU/mL and = 2,000 IU/mL over time 6.Including but not limited to: Change from baseline in quantitative HBsAg, anti-HBs, HBeAg, anti-HBe, anti-HBc, Hepatitis B core-related antigen (HBcrAg), HBV Ribonucleic acid (RNA), and HBV DNA levels over time 7.Estimated PK parameters from sparse sampling and population PK models NMEs and NUCs 8.Incidence, nature, and severity of AEs and laboratory abnormalities over time 9.Analyses of PK/PD data 10.Relationship between ADA status, PK, safety, PD, and efficacy ;Timepoint(s) of evaluation of this end point: 1-3. Up to Week 96 4. Baseline (Day 1) up to Week 96 5. Up to Week 96 6. Baseline (Day 1) up to Week 96 7. NME PK: Day 1 up to Week 49 and at virological breakthrough/relapse. NUC PK: Day 1 up to Week 49 and at virological breakthrough/relapse 8 - 10. Up to Week 96 | — |
Countries
Canada, China, France, Hong Kong, Korea, Republic of, New Zealand, Spain, Taiwan, Thailand, United Kingdom
Contacts
Public ContactTrial Information Support Line-TISL
F. Hoffmann-La Roche Ltd
Outcome results
None listed