Effect of RO6871765 and RO7011785 on Immune Response With the Stimulation of Peripheral Blood Mononuclear Cells (PBMCs) in Chinese Healthy Volunteers and Chronic Hepatitis B Patients

Study Overview
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Brief Summary
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This is an exploratory study to characterize the ex vivo immune response to RO6871765 or RO7011785 stimulation of peripheral blood mononuclear cells (PBMCs) extracted from healthy volunteers and chronic hepatitis B (CHB) patients.

Conditions
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Hepatitis B, Chronic

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: All population: Chinese population Adequate hematological function: platelet count greater than or equal to (>=) 100*10^9 per liter (/L), hemoglobin (Hb) >= 12 grams/deciliter (g/dL) (male) or >= 11 g/dL (female), white blood cell (WBC) count >= 4*10^9/L and <= 11*10^9/L Healthy volunteers: Absence of evidence of any active or chronic disease Negative hepatitis B virus deoxyribonucleic acid (HBV DNA), hepatitis B surface antigen (HBsAg), hepatitis B surface antibody (HBsAb), hepatitis B envelope antigen (HBeAg), hepatitis B envelope antiody (HBeAb) and hepatitis B core antibody (HBcAb) Adequate liver function: transaminases alanine aminotransferase (ALT) <= 1.0 times the upper limit of normal (ULN) Treatment naïve CHB patients: HBsAg-positive (>=250 international unit/milliliter [IU/mL]), compensated liver function, non-cirrhotic HBeAg-positive, HBV DNA >= 200,000 IU/ml or equivalent copies/mL, ALT >1.5 times the ULN and ALT <8 times the ULN HBeAg-negative nucleoside/nucleotide analogue-treated CHB patients: Subjects who HBeAg-seroconverted on nucleoside/nucleotide analogue therapy (treatment for 1 to 3 years prior to enrollment) with HBV DNA <90 IU/mL or below a detection level acceptable by both the sponsor and investigator for at least the preceding 6 months; HBeAg negative and HBeAb positive HBsAg-positive (>=250 IU/mL), compensated liver function, non-cirrhotic -ALT <= 1*ULN Exclusion Criteria: Use of steroids or other immune suppressive agents within the last 4 weeks that would impact the number/functions of white blood cells (WBC) Any other diseases or clinical laboratory finding giving reasonable suspicion of a disease or condition (including, but not limited to, cancer, lupus erythematosus, rheumatoid arthritis, or other autoimmune disease) that could confound the result of the study Positive Hepatitis A immunoglobulin M (IgM) antibody, Hepatitis C antibody (HCV Ab) or human immunodeficiency virus (HIV) at screening Significant acute infection, example; influenza, acute gastrointestinal symptoms or any other clinically significant illness within 2 weeks Previous/concurrent treatment with interferon-based therapy for CHB

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Healthy volunteers<br>Blood samples from healthy volunteers will be collected for ex vivo stimulation and for further sample preparation and analysis. | |
| Nucleoside/nucleotide analogue-treated CHB patients<br>Blood samples from nucleoside/nucleotide analogue-treated CHB patients will be collected for ex vivo stimulation and for further sample preparation and analysis. | |
| Treatment-naive CHB patients<br>Blood samples from treatment-naïve CHB patients will be collected for ex vivo stimulation and for further sample preparation and analysis. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Correlation coefficients between baseline toll-like receptor 7 (TLR7) expression and ex vivo immune response upon stimulation of PBMCs with RO6871765 or RO7011785 (in terms of cytokine release and gene expression) |  | Day 1 | 
| Cytokine/chemokine production |  | Day 1 | 
| Induction of interferon-responsive genes |  | Day 1 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number or percentages of T-lymphocytes in healthy volunteers and subjects with CHB |  | Screening Up to Day 1 | 
| Number or percentages of B-lymphocytes in healthy volunteers and subjects with CHB |  | Screening up to Day 1 | 
| Number or percentages of natural killer (NK) -cells in healthy volunteers and subjects with CHB |  | Screening up to Day 1 | 
| Number or percentages of myeloid dendritic cells (mDCs) in healthy volunteers and subjects with CHB |  | Screening up to Day 1 | 
| Number or percentages of plasmacytoid dendritic cells (pDCs) in healthy volunteers and subjects with CHB |  | Screening up to Day 1 | 
| Ex-vivo antiviral activity of PBMC supernatant |  | Day 1 |