Clinical trial NCT02498275: 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 type: OBSERVATIONAL
Overall status: TERMINATED
Conditions: Hepatitis B, Chronic
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2015-07-15
Enrollment: 14
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: CROSS_SECTIONAL
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Chinese population: healthy volunteers, treatment naive CHB patients and nucleoside or nucleotide analogue treated CHB patients

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: 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)
timeFrame: Day 1
measure: Cytokine/chemokine production
timeFrame: Day 1
measure: Induction of interferon-responsive genes
timeFrame: Day 1
Secondary outcomes:
measure: Number or percentages of T-lymphocytes in healthy volunteers and subjects with CHB
timeFrame: Screening Up to Day 1
measure: Number or percentages of B-lymphocytes in healthy volunteers and subjects with CHB
timeFrame: Screening up to Day 1
measure: Number or percentages of natural killer (NK) -cells in healthy volunteers and subjects with CHB
timeFrame: Screening up to Day 1
measure: Number or percentages of myeloid dendritic cells (mDCs) in healthy volunteers and subjects with CHB
timeFrame: Screening up to Day 1
measure: Number or percentages of plasmacytoid dendritic cells (pDCs) in healthy volunteers and subjects with CHB
timeFrame: Screening up to Day 1
measure: Ex-vivo antiviral activity of PBMC supernatant
timeFrame: Day 1
Other outcomes:
Locations:
city: Shanghai
country: China
city: Shanghai
country: China
city: Shanghai
country: China
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References: