A Study of ALN-HBV in Healthy Adult Volunteers and Non-cirrhotic Patients With Chronic Hepatitis B Virus (HBV) Infection
Primary Purpose
Hepatitis B, Chronic Hepatitis B, Hepatitis B, Chronic
Status
Terminated
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
ALN-HBV
Sterile Normal Saline (0.9% NaCl)
Sponsored by
About this trial
This is an interventional treatment trial for Hepatitis B focused on measuring RNAi therapeutic, Hepatitis B, Chronic Hepatitis B, Hepatitis B, Chronic, Hepatitis B Infection, HBV
Eligibility Criteria
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
Sites / Locations
- Clinical Trial Site
- Clinical Trial Site
- Clinical Trial Site
- Clinical Trial Site
- Clinical Trial Site
- Clinical Trial Site
- Clinical Trial Site
- Clinical Trial Site
- Clinical Trial Site
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Placebo Comparator
Arm Label
ALN-HBV
Sterile Normal Saline (0.9% NaCl)
Arm Description
Outcomes
Primary Outcome Measures
Proportion of subjects experiencing adverse events
Secondary Outcome Measures
Profile of Pharmacokinetics (PK) of ALN-HBV
Maximum plasma concentration (Cmax)
Profile of Pharmacokinetics (PK) of ALN-HBV
Elimination half-life (t1/2)
Profile of Pharmacokinetics (PK) of ALN-HBV
Area under the concentration-time curve (AUC)
Change from baseline in quantitative hepatitis B surface antigen (HBsAg) levels
Change in HBsAg levels from baseline
Full Information
NCT ID
NCT02826018
First Posted
July 5, 2016
Last Updated
September 20, 2018
Sponsor
Alnylam Pharmaceuticals
1. Study Identification
Unique Protocol Identification Number
NCT02826018
Brief Title
A Study of ALN-HBV in Healthy Adult Volunteers and Non-cirrhotic Patients With Chronic Hepatitis B Virus (HBV) Infection
Official Title
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
Study Type
Interventional
2. Study Status
Record Verification Date
September 2018
Overall Recruitment Status
Terminated
Study Start Date
June 24, 2016 (undefined)
Primary Completion Date
October 2017 (Actual)
Study Completion Date
October 2017 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Alnylam Pharmaceuticals
4. Oversight
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hepatitis B, Chronic Hepatitis B, Hepatitis B, Chronic, Hepatitis B Infection, HBV
Keywords
RNAi therapeutic, Hepatitis B, Chronic Hepatitis B, Hepatitis B, Chronic, Hepatitis B Infection, HBV
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
Participant
Allocation
Randomized
Enrollment
24 (Actual)
8. Arms, Groups, and Interventions
Arm Title
ALN-HBV
Arm Type
Active Comparator
Arm Title
Sterile Normal Saline (0.9% NaCl)
Arm Type
Placebo Comparator
Intervention Type
Drug
Intervention Name(s)
ALN-HBV
Intervention Description
Ascending doses of ALN-HBV by subcutaneous (sc) injection
Intervention Type
Drug
Intervention Name(s)
Sterile Normal Saline (0.9% NaCl)
Intervention Description
Calculated volume to match active comparator
Primary Outcome Measure Information:
Title
Proportion of subjects experiencing adverse events
Time Frame
Part A (SAD phase): through Day 29; Part B (SAD phase): through Day 85; Part C (MAD phase): through Day 176
Secondary Outcome Measure Information:
Title
Profile of Pharmacokinetics (PK) of ALN-HBV
Description
Maximum plasma concentration (Cmax)
Time Frame
Part A (SAD phase): Day 1; Part B (SAD phase): Day 1; Part C (MAD phase): Days 1 and 85
Title
Profile of Pharmacokinetics (PK) of ALN-HBV
Description
Elimination half-life (t1/2)
Time Frame
Part A (SAD phase): Day 1; Part B (SAD phase): Day 1; Part C (MAD phase): Days 1 and 85
Title
Profile of Pharmacokinetics (PK) of ALN-HBV
Description
Area under the concentration-time curve (AUC)
Time Frame
Part A (SAD phase): Day 1; Part B (SAD phase): Day 1; Part C (MAD phase): Days 1 and 85
Title
Change from baseline in quantitative hepatitis B surface antigen (HBsAg) levels
Description
Change in HBsAg levels from baseline
Time Frame
Part B (SAD phase): baseline through Day 85; Part C (MAD phase): baseline through Day 176
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Stephen Huang, MD
Organizational Affiliation
Alnylam Pharmaceuticals
Official's Role
Study Director
Facility Information:
Facility Name
Clinical Trial Site
City
Adelaide
State/Province
South Australia
Country
Australia
Facility Name
Clinical Trial Site
City
Fitzroy
State/Province
Victoria
Country
Australia
Facility Name
Clinical Trial Site
City
Parkville
State/Province
Victoria
Country
Australia
Facility Name
Clinical Trial Site
City
Hong Kong
Country
Hong Kong
Facility Name
Clinical Trial Site
City
Seoul
ZIP/Postal Code
03080
Country
Korea, Republic of
Facility Name
Clinical Trial Site
City
Seoul
ZIP/Postal Code
05505
Country
Korea, Republic of
Facility Name
Clinical Trial Site
City
Auckland
Country
New Zealand
Facility Name
Clinical Trial Site
City
Singapore
Country
Singapore
Facility Name
Clinical Trial Site
City
London
Country
United Kingdom
12. IPD Sharing Statement
Learn more about this trial
A Study of ALN-HBV in Healthy Adult Volunteers and Non-cirrhotic Patients With Chronic Hepatitis B Virus (HBV) Infection
We'll reach out to this number within 24 hrs