A Study of ALN-HBV in Healthy Adult Volunteers and Non-cirrhotic Patients With Chronic Hepatitis B Virus (HBV) Infection

Phase 1

Terminated

• Conditions: Hepatitis B; Chronic Hepatitis B; Hepatitis B, Chronic; Hepatitis B Infection; HBV
• Interventions: Drug: ALN-HBV; Drug: Sterile Normal Saline (0.9% NaCl)

• Registration Number: NCT02826018
• Lead Sponsor: Alnylam Pharmaceuticals

Brief Summary

The purpose of this study is to determine the safety, tolerability and pharmacokinetics of ALN-HBV in healthy adult volunteers and patients with chronic hepatitis B virus (HBV) infection. In addition, the study will assess antiviral efficacy of ALN-HBV in patients with HBV.

Detailed Description

The study has 3 parts. Part A is a single ascending dose (SAD) study in healthy volunteers. Part B is a single ascending dose study (SAD) in patients with HBV infection. Part C is a multiple ascending dose study (MAD) in patients with HBV infection.

Study Timeline

• Study Start: 2016-06-24
• Study First Submitted: 2016-07-05
• Study First Submitted QC: 2016-07-06
• Study First Posted: 2016-07-07
• Primary Completion: 2017-10
• Study Completion: 2017-10
• Status Verified: 2018-09
• Last Update Submitted: 2018-09-20
• Last Update Posted: 2018-09-24

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 24

Inclusion Criteria

All subjects:

• 18 to 65 years inclusive
• 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
• Agrees not to donate blood during the duration of the study
• Willing to comply with the study requirements and to provide written informed consent

Additional inclusion criteria for patients with HBV infection:

• Body mass index (BMI) ≥18.0 kg/m2
• Must be on a stable regimen of entecavir or tenofovir

Exclusion Criteria

All subjects:

• Any uncontrolled or serious disease, or any medical or surgical condition, that may either interfere with participation in the clinical study, and/or put the subject at significant risk
• Subjects with a history of serious mental illness
• Active infection with human immunodeficiency virus (HIV) infection, hepatitis A virus (HAV), or hepatitis C virus (HCV) infection and/or a history of delta virus hepatitis
• Known hypersensitivity or contraindication to any medication or history of allergic reaction to an oligonucleotide or N-acetylgalactosamine (GalNAc)

Additional exclusion criteria for healthy volunteers:

• Evidence of liver disease

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
ALN-HBV	ALN-HBV	-
Sterile Normal Saline (0.9% NaCl)	Sterile Normal Saline (0.9% NaCl)	-

Primary Outcome Measures

Name	Time	Method
Proportion of subjects experiencing adverse events	Part A (SAD phase): through Day 29; Part B (SAD phase): through Day 85; Part C (MAD phase): through Day 176

Secondary Outcome Measures

Name	Time	Method
Profile of Pharmacokinetics (PK) of ALN-HBV	Part A (SAD phase): Day 1; Part B (SAD phase): Day 1; Part C (MAD phase): Days 1 and 85	Area under the concentration-time curve (AUC)
Change from baseline in quantitative hepatitis B surface antigen (HBsAg) levels	Part B (SAD phase): baseline through Day 85; Part C (MAD phase): baseline through Day 176	Change in HBsAg levels from baseline

Trial Locations

Locations (1)

Clinical Trial Site; 🇬🇧 London, United Kingdom