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

Study Overview
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Brief Summary
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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
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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.

Official Title
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A Phase 1/2, Randomized, Single-Blind, Placebo-Controlled, Single-Ascending and Multiple-Ascending Dose, Safety, Tolerability, Pharmacokinetics, and Antiviral Efficacy Study of Subcutaneously Administered ALN-HBV in Healthy Adult Subjects and Non-cirrhotic Patients With Chronic Hepatitis B Virus (HBV) Infection

Conditions
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Hepatitis B, Chronic Hepatitis B, Hepatitis B, Chronic, Hepatitis B Infection, HBV

Intervention / Treatment
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* Drug: ALN-HBV
* Drug: Sterile Normal Saline (0.9% NaCl)


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: ALN-HBV<br> | Drug: ALN-HBV<br>* Ascending doses of ALN-HBV by subcutaneous (sc) injection<br>|
| Placebo Comparator: Sterile Normal Saline (0.9% NaCl)<br> | Drug: Sterile Normal Saline (0.9% NaCl)<br>* Calculated volume to match active comparator<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Profile of Pharmacokinetics (PK) of ALN-HBV | Maximum plasma concentration (Cmax) | Part A (SAD phase): Day 1; Part B (SAD phase): Day 1; Part C (MAD phase): Days 1 and 85 | 
| Profile of Pharmacokinetics (PK) of ALN-HBV | Elimination half-life (t1/2) | Part A (SAD phase): Day 1; Part B (SAD phase): Day 1; Part C (MAD phase): Days 1 and 85 | 
| Profile of Pharmacokinetics (PK) of ALN-HBV | Area under the concentration-time curve (AUC) | Part A (SAD phase): Day 1; Part B (SAD phase): Day 1; Part C (MAD phase): Days 1 and 85 | 
| Change from baseline in quantitative hepatitis B surface antigen (HBsAg) levels | Change in HBsAg levels from baseline | Part B (SAD phase): baseline through Day 85; Part C (MAD phase): baseline through Day 176 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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RNAi therapeutic, Hepatitis B, Chronic Hepatitis B, Hepatitis B, Chronic, Hepatitis B Infection, HBV