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

Hepatitis B, Chronic Clinical Trial

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02498275
• Other study ID #: YP29018
• Status: Terminated
• Phase: N/A
• First received: July 13, 2015
• Last updated: November 4, 2016
• Start date: July 2014
• Est. completion date: August 2014

Study information

• Verified date: November 2016
• Source: Hoffmann-La Roche
• Contact: n/a
• Is FDA regulated: No
• Health authority: Not Required: as study is exploratory research (not a clinical study)
• Study type: Observational

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 14
• Est. completion date: August 2014
• Est. primary completion date: August 2014
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

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

Study Design

Observational Model: Case Control, Time Perspective: Cross-Sectional

Related Conditions & MeSH terms

• Hepatitis
• Hepatitis B
• Hepatitis B, Chronic

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Primary	Cytokine/chemokine production		Day 1	No
Primary	Induction of interferon-responsive genes		Day 1	No
Secondary	Number or percentages of T-lymphocytes in healthy volunteers and subjects with CHB		Screening Up to Day 1	No
Secondary	Number or percentages of B-lymphocytes in healthy volunteers and subjects with CHB		Screening up to Day 1	No
Secondary	Number or percentages of natural killer (NK) -cells in healthy volunteers and subjects with CHB		Screening up to Day 1	No
Secondary	Number or percentages of myeloid dendritic cells (mDCs) in healthy volunteers and subjects with CHB		Screening up to Day 1	No
Secondary	Number or percentages of plasmacytoid dendritic cells (pDCs) in healthy volunteers and subjects with CHB		Screening up to Day 1	No
Secondary	Ex-vivo antiviral activity of PBMC supernatant		Day 1	No