The First-in-Human Study of an Investigational Drug, ALN-HBV, in Healthy Adult Subjects and Patients with Chronic Hepatitis B Virus (HBV) Infectio

Phase 1

• Conditions: Chronic Hepatitis B virus (HBV) Infection; MedDRA version: 18.1Level: PTClassification code 10008910Term: Chronic hepatitis BSystem Organ Class: 10021881 - Infections and infestations; Therapeutic area: Diseases [C] - Immune System Diseases [C20]

• Registration Number: EUCTR2015-004360-10-GB
• Lead Sponsor: Alnylam Pharmaceuticals, Inc

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2016-02-24
• Last Update Posted: 3 September 2018

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 142

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
Additional Inclusion Criteria for Part D
14. Body mass index (BMI) =18.0 kg/m2 and =32 kg/m2 as assessed at Screening.
16. Chronic HBV infection as evidenced by a screening HBV DNA level >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 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) < 60 mL/min/1.73 m2 at screening.

Additional Exclusion Criteria for Part A (Healthy Adult Subjects)
21. Known history of chronic liver disease.
22. Clinical laboratory evidence or clinical diagnosis of chronic hepatitis B virus (HBV) infection as shown by HBsAg positivity in blood.
23. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) above the normal range; alkaline phosphatase (ALP), or albumin outside the reference range and considered clinically relevant in the opinion of the Investigator at screening.

Additional Exclusion Criteria for Parts B and C
27. History of chronic liver disease from any cause other than chronic HBV infection.
28. History of cirrhosis.
29. History of hepatic decompensation, including ascites, hepatic encephalopathy and/or esophageal or gastric varices.
30. Screening ALT level >3×ULN.
31. Serum albumin level < lower limit of normal at screening.
32. Platelet count =100,000 per microliter at screening.
33. Absolute neutrophil count (ANC) <1500 cells/µL at screening.
34. International normalized ratio (INR) or prothrombin time (PT) above the upper limit of the normal reference range (as per the local laboratory reference range) at screening.

Additional Exclusion Criteria for Part D
35. History of chronic liver disease from any cause other than CHB.
36. History of cirrhosis.
37. History of hepatic decompensation including ascites, hepatic encephalopathy and/or esophageal or gastric varices.
38. Screening ALT 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.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified