Clinical trial NCT02826018: 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
Overall status: TERMINATED
Phase: PHASE1
Conditions: 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
Lead sponsor: Alnylam Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2016-07-07
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Proportion of subjects experiencing adverse events
timeFrame: Part A (SAD phase): through Day 29; Part B (SAD phase): through Day 85; Part C (MAD phase): through Day 176
Secondary outcomes:
measure: Profile of Pharmacokinetics (PK) of ALN-HBV
timeFrame: Part A (SAD phase): Day 1; Part B (SAD phase): Day 1; Part C (MAD phase): Days 1 and 85
measure: Profile of Pharmacokinetics (PK) of ALN-HBV
timeFrame: Part A (SAD phase): Day 1; Part B (SAD phase): Day 1; Part C (MAD phase): Days 1 and 85
measure: Profile of Pharmacokinetics (PK) of ALN-HBV
timeFrame: Part A (SAD phase): Day 1; Part B (SAD phase): Day 1; Part C (MAD phase): Days 1 and 85
measure: Change from baseline in quantitative hepatitis B surface antigen (HBsAg) levels
timeFrame: Part B (SAD phase): baseline through Day 85; Part C (MAD phase): baseline through Day 176
Other outcomes:
Locations:
city: Adelaide
country: Australia
facility: Clinical Trial Site
state: South Australia
city: Fitzroy
country: Australia
facility: Clinical Trial Site
state: Victoria
city: Parkville
country: Australia
facility: Clinical Trial Site
state: Victoria
city: Hong Kong
country: Hong Kong
facility: Clinical Trial Site
city: Seoul
country: Korea, Republic of
facility: Clinical Trial Site
city: Seoul
country: Korea, Republic of
facility: Clinical Trial Site
city: Auckland
country: New Zealand
facility: Clinical Trial Site
city: Singapore
country: Singapore
facility: Clinical Trial Site
city: London
country: United Kingdom
facility: Clinical Trial Site
Study officials:
affiliation: Alnylam Pharmaceuticals
name: Stephen Huang, MD
role: STUDY_DIRECTOR
References: