Chronic Hepatitis B virus (HBV) Infection MedDRA version: 18.1 Level: PT Classification code 10008910 Term: Chronic hepatitis B System Organ Class: 10021881 - Infections and infestations
Conditions
Interventions
Product Name: ALN-HBV
Product Code: ALN-HBV
Pharmaceutical Form: Solution for injection
INN or Proposed INN: ALN-66810
Current Sponsor code: ALN-66810
Concentration unit: mg/ml milligram(s)/millilitre
Sponsors
Alnylam Pharmaceuticals, Inc
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Inclusion Criteria for Parts A, B, C and D 1. Age 18 (or age of legal consent, whichever is older) to 65 years, inclusive 2. 12-lead electrocardiogram (ECG) within normal limits or with no clinically significant abnormalities at screening and Day -1 in the opinion of the Investigator. 3. Women of child-bearing potential must have a negative pregnancy test, cannot be breast feeding, and must be willing to use a highly effective method of contraception 14 days before first dose, throughout study participation, and for 90 days after last dose administration. Additional Inclusion Criteria for Part A 7. Body mass index (BMI) =18.0 kg/m2 and =30 kg/m2 as assessed at screening. Additional Inclusion Criteria for Parts B and C 8. Body mass index (BMI) =18.0 kg/m2 and =32 kg/m2 as assessed at screening. 10. Chronic HBV infection as evidenced by a screening HBsAg level > 500 IU/mL. 11. A history of treatment with only one HBV polymerase inhibitor, entecavir or tenofovir. 12. Taking entecavir or tenofovir for at least 12 months prior to screening without an interruption of 7 or more consecutive days over this time period. 13. Screening HBV DNA below the lower limit of quantitation (100 IU/mL in the last 6 months. Only a single HBV DNA measure that is =LLOQ but =100 IU/mL in the last 6 months is permitted provided that the subsequent HBV DNA level is 2,000 IU/mL and screening HBsAg level that is >500 IU/mL. 17. The patient has not previously received any anti-HBV treatment. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 142 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: Exclusion Criteria for Parts A, B, C and D 5. Systolic blood pressure >140 mmHg and a diastolic blood pressure of >90 mmHg after 10 minutes supine rest at screening. 6. Indirect bilirubin > 1.5 × ULN and direct bilirubin > ULN at screening. 9. Active infection with human immunodeficiency virus (HIV) infection or hepatitis C virus (HCV) infection and/or a history of delta virus hepatitis. 11. History or clinical evidence of alcohol and/or drug abuse, within the 12 months before screening. 13. Known hypersensitivity or contraindication to any medication or history of allergic reaction to an oligonucleotide or N-acetylgalactosamine (GalNAc). 15. History of intolerance to SC injection or relevant abdominal scarring (surgical, burns, etc.). 20. Estimated glomerular filtration rate (using MDRD equation) 3×ULN. 31. Serum albumin level 5×ULN. 39. Serum albumin level < lower limit of normal at screening. 40. Platelet count =100,000 per microliter at screening. 41. ANC <1500 cells/µL at screening. 42. INR or PT above the upper limit of the normal reference range (as per the local laboratory reference range) at screening.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: Part A: assessed throughout to Day 29. Part B: assessed throughout to Day 85 and up to Day 169, or until HBsAg level is <1 log10 IU/mL below the Day 1 value, whichever duration is shorter. Part C & D: assessed throughout to Day 176 and up to Day 260, or until HBsAg level is <1 log10 IU/mL below the Day 1 value, whichever duration is shorter.;Main Objective: To evaluate the safety and tolerability of single or multiple doses of ALN-HBV in healthy adult subjects and non-cirrhotic patients with chronic HBV infection when administered as monotherapy or concomitantly with the anti-HBV nucleoside, entecavir, or the anti-HBV nucleotide, tenofovir;Primary end point(s): - Incidence of adverse events - Clinical laboratory test results;Secondary Objective: - To characterize the PK of ALN-HBV in healthy adult subjects and non-cirrhotic patients with chronic HBV infection. - To assess the antiviral efficacy of ALN-HBV in non-cirrhotic patients with chronic HBV infection who are receiving anti-HBV NUC treatment (Parts B and C) or who are anti-HBV treatment naïve (Part D) as measured by changes in HBV DNA and HBsAg levels | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary Endpoint for Parts A, B, C, and D (All Subjects) - Pharmacokinetic parameters of ALN-HBV and possible metabolites (may include, but not be limited to, maximum plasma concentration, time to reach maximum plasma concentration, area under the plasma concentration versus time curve, apparent terminal elimination half-life, fraction eliminated in the urine, and renal clearance) Secondary Endpoints for Parts B, C and D only (HBV Patients) - Change in the levels of HBsAg in blood - Change in the levels of HBV DNA in blood;Timepoint(s) of evaluation of this end point: Part A: assessed throughout to Day 29. Part B: assessed throughout to Day 85 and up to Day 169, or until HBsAg level is <1 log10 IU/mL below the Day 1 value, whichever duration is shorter. Part C & D: assessed throughout to Day 176 and up to Day 260, or until HBsAg level is <1 log10 IU/mL below the Day 1 value, whichever duration is shorter. | — |
Countries
Australia, Hong Kong, Korea, Republic of, New Zealand, Singapore, Taiwan, United Kingdom
Contacts
Public ContactClinical Trial Hotline
Alnylam Pharmaceuticals, Inc
Outcome results
None listed