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

• Sponsor: Alnylam Pharmaceuticals (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT02826018
• Collaborator: (none)
• Enrollment: 24
• Locations: 9
• Arms: 2
• Duration (Months): 15.2
• Patients Per Site: 2.7
• Patients Per Site Per Month: 0.2

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Hepatitis B; Chronic Hepatitis B; Hepatitis B, Chronic; Hepatitis B Infection; HBV	Drug: ALN-HBV; Drug: Sterile Normal Saline (0.9% NaCl)	Phase 1

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 Design

• Study Type: Interventional
• Actual Enrollment: 24 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Participant)
• Primary Purpose: Treatment
• 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 Start Date: Jun 24, 2016
• Actual Primary Completion Date: Oct 1, 2017
• Actual Study Completion Date: Oct 1, 2017

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. 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

1. 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]

   Maximum plasma concentration (Cmax)

2. 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]

   Elimination half-life (t1/2)

3. 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)

4. 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

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Clinical Trial Site	Adelaide	South Australia	Australia
2	Clinical Trial Site	Fitzroy	Victoria	Australia
3	Clinical Trial Site	Parkville	Victoria	Australia
4	Clinical Trial Site	Hong Kong		Hong Kong
5	Clinical Trial Site	Seoul		Korea, Republic of	03080
6	Clinical Trial Site	Seoul		Korea, Republic of	05505
7	Clinical Trial Site	Auckland		New Zealand
8	Clinical Trial Site	Singapore		Singapore
9	Clinical Trial Site	London		United Kingdom

Sponsors and Collaborators

• Alnylam Pharmaceuticals

Investigators

• Study Director: Stephen Huang, MD, Alnylam Pharmaceuticals

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Alnylam Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT02826018
• Other Study ID Numbers: ALN-HBV-001
• First Posted: Jul 7, 2016
• Last Update Posted: Sep 24, 2018
• Last Verified: Sep 1, 2018

• Keywords provided by Alnylam Pharmaceuticals: RNAi therapeutic; Hepatitis B; Chronic Hepatitis B; Hepatitis B, Chronic; Hepatitis B Infection; HBV
• Additional relevant MeSH terms: Infections; Communicable Diseases; Hepatitis A; Hepatitis B; Hepatitis B, Chronic; Hepatitis; Hepatitis, Chronic

Study Results

No Results Posted as of Sep 24, 2018