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

Hepatitis B Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02826018
• Other study ID #: ALN-HBV-001
• Status: Terminated
• Phase: Phase 1
• Start date: June 24, 2016
• Est. completion date: October 2017

Study information

• Verified date: September 2018
• Source: Alnylam Pharmaceuticals
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 24
• Est. completion date: October 2017
• Est. primary completion date: October 2017
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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

Related Conditions & MeSH terms

• Chronic Hepatitis B
• Communicable Diseases
• HBV
• Hepatitis
• Hepatitis A
• Hepatitis B
• Hepatitis B Infection
• Hepatitis B, Chronic
• Hepatitis, Chronic
• Infection

Intervention

Drug:
• ALN-HBV
Ascending doses of ALN-HBV by subcutaneous (sc) injection
• Sterile Normal Saline (0.9% NaCl)
Calculated volume to match active comparator

Locations

Country	Name	City	State
Australia	Clinical Trial Site	Adelaide	South Australia
Australia	Clinical Trial Site	Fitzroy	Victoria
Australia	Clinical Trial Site	Parkville	Victoria
Hong Kong	Clinical Trial Site	Hong Kong
Korea, Republic of	Clinical Trial Site	Seoul
Korea, Republic of	Clinical Trial Site	Seoul
New Zealand	Clinical Trial Site	Auckland
Singapore	Clinical Trial Site	Singapore
United Kingdom	Clinical Trial Site	London

Sponsors (1)

Lead Sponsor	Collaborator
Alnylam Pharmaceuticals

Countries where clinical trial is conducted

Australia,  Hong Kong,  Korea, Republic of,  New Zealand,  Singapore,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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