Chronic hepatitis B virus Infections and Infestations Chronic viral hepatitis
Conditions
Interventions
Patients will visit the clinic a total of 20 times over the one year treatment period.
M04NM11 or placebo will be administered orally in escalating doses of 10^8 CFU, 10^9 CFU and 10^10 CFU within ea
Sponsors
Emergent Product Development UK Ltd (UK)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Participating patients must be over 18 years of age, either sex 2. Have been hepatitis B surface antigen (HBsAg) positive for at least six months 3. A detailed medical history demonstrating stable alanine aminotransferase (ALT), prothrombin time (PT) and serum bilirubin and a liver biopsy in the previous 24 months 4. Patients will be stratified and recruited according to hepatitis B 'e' antigen (HBeAg) status and viral deoxyribonucleic acid (DNA) load
Exclusion criteria
Exclusion criteria: 1. Have any hypersensitivity to the investigational medicinal product (IMP) 2. Are hepatitis C virus (HCV) or hepatitis D virus (HDV) positive 3. Are receiving or have received medication for their hepatitis B in the previous 12 months 4. Have evidence of hepatic decompensation, cirrhosis or ALT greater than 5.1 x upper limit of normal (ULN), PT greater than 1.25 x ULN or total bilirubin greater than 1.5 x ULN 5. Immuno-suppression or close contact with immuno-suppressed people
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 1. The incidence of clinically significant changes in serum biochemistry and haematology tests, particularly elevations of ALT or bilirubin, or prolongation of PT 2. The incidence of adverse events, including flu-like symptoms, attributable to the investigational product 3. The incidence of serious adverse events attributable to the investigational product The primary outcome measures will be at screening; on days 3, 7, 14 and 28 after the first dose; days 7, 14 and 28 after the second dose and days 14 and 28 after subsequent doses. Following receipt of the final dose, patients will be followed up for a further 20 weeks up to day 308. | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. The proportion of patients in each group who experience a decrease in HBV DNA load of greater than or equal to 2 log10, or a reduction to less than 10 x 4 copies/mL, maintained until day 168 (28 days after the final dose) 2. The proportion of patients in groups 1 and 2 who become HBeAg negative at any study visit before day 168 (28 days after the final dose) 3. The proportion of patients in each group who were negative for anti-HBe at baseline, who have anti-HBe at day 168 (28 days after the final dose), or if patients were anti-HBe positive at baseline the proportion who have a four-fold increase in anti-HBe titre at day 168 4. The proportion of patients in each group with normal ALT levels by day 168 5. The proportion of patients in each group who demonstrate a significant change in the frequency of HBV specific interferon gamma producing T cells determined by enzyme-linked immunosorbent spot (ELISPOT) assay or by intracellular cytokine staining 6. The proportion of patients who maintain a treatment effect in the follow up period as demonstrated by maintenance of the reduction in HBV DNA load achieved during the treatment period, maintenance of HBeAg negative status or conversion to HBeAg negative status between days 196 and 308 (two to six months after the last dose) | — |
Countries
Serbia, United Kingdom
Outcome results
None listed