- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03672188
Study of VIR-2218 in Healthy Subjects and Patients With Chronic Hepatitis B
A Phase 1/2, Randomized, Placebo-Controlled Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Antiviral Activity of VIR-2218
This is a phase 1/2 study in which healthy adult subjects and subjects with chronic hepatitis B virus (HBV) infection will receive VIR-2218 or placebo and will be assessed for safety, tolerability, pharmacokinetics, and antiviral activity (only in subjects with chronic HBV).
In the single ascending dose (SAD) part, Part A, healthy adult subjects will receive one dose of VIR-2218 or placebo, administered subcutaneously (SC). In the multiple ascending dose (MAD) parts, Part B & Part C, subjects with chronic HBV infection will receive two doses of VIR-2218 or placebo every 4 weeks administered SC.
Study Overview
Status
Conditions
Intervention / Treatment
Study Type
Enrollment (Actual)
Phase
- Phase 2
- Phase 1
Contacts and Locations
Study Locations
-
-
Queensland
-
Birtinya, Queensland, Australia, 4575
- Investigative Site
-
-
Victoria
-
Clayton, Victoria, Australia, 3168
- Investigative Site
-
Fitzroy, Victoria, Australia, 3065
- Investigative Site
-
-
-
-
-
Hong Kong, Hong Kong
- Investigative Site
-
-
-
-
-
Busan, Korea, Republic of, 49241
- Investigative Site
-
Seoul, Korea, Republic of, 03080
- Investigative Site
-
Seoul, Korea, Republic of, 05505
- Investigative Site
-
-
-
-
-
Auckland, New Zealand, 1010
- Investigative Site
-
Auckland, New Zealand, 2025
- Investigative Site
-
-
-
-
-
Bangkok, Thailand, 10330
- Investigative Site
-
Bangkok, Thailand, 10400
- Investigative Site
-
Bangkok, Thailand, 10700
- Investigative Site
-
Hat Yai, Thailand, 90110
- Investigative Site
-
Khon Kaen, Thailand, 40002
- Investigative Site
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Part A SAD:
Inclusion Criteria:
- Male or female age 18 - 55
- BMI 18 - 32 kg/m^2
Exclusion Criteria:
- Any clinically significant chronic or acute medical condition that makes the volunteer unsuitable for participation
- History or evidence of drug or alcohol abuse
- History of intolerance to SC injection
Parts B/C MAD:
Inclusion Criteria:
- Male or female age 18 - 65
- BMI 18 - 32 kg/m^2
- Chronic HBV infection for >/= 6 months
Exclusion Criteria:
- Any clinically significant chronic or acute medical condition that makes the volunteer unsuitable for participation
- Significant fibrosis or cirrhosis
- History or evidence of drug or alcohol abuse
- History of intolerance to SC injection
- History of chronic liver disease from any cause other than chronic HBV infection
- History of hepatic decompensation
Study Plan
How is the study designed?
Design Details
- Primary Purpose: TREATMENT
- Allocation: RANDOMIZED
- Interventional Model: PARALLEL
- Masking: QUADRUPLE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
EXPERIMENTAL: Part A: SAD VIR-2218 50 mg
Healthy subjects received a single dose of VIR-2218 of 50 mg administered SC
|
VIR-2218 given by subcutaneous injection
|
EXPERIMENTAL: Part A: SAD VIR-2218 100 mg
Healthy subjects received a single dose of VIR-2218 of 100 mg administered SC
|
VIR-2218 given by subcutaneous injection
|
EXPERIMENTAL: Part A: SAD VIR-2218 200 mg
Healthy subjects received a single dose of VIR-2218 of 200 mg administered SC
|
VIR-2218 given by subcutaneous injection
|
EXPERIMENTAL: Part A: SAD VIR-2218 400 mg
Healthy subjects received a single dose of VIR-2218 of 400 mg administered SC
|
VIR-2218 given by subcutaneous injection
|
EXPERIMENTAL: Part A: SAD VIR-2218 600 mg
Healthy subjects received a single dose of VIR-2218 of 600 mg administered SC
|
VIR-2218 given by subcutaneous injection
|
EXPERIMENTAL: Part A: SAD VIR-2218 900 mg
Healthy subjects received a single dose of VIR-2218 of 900 mg administered SC
|
VIR-2218 given by subcutaneous injection
|
PLACEBO_COMPARATOR: Part A: SAD Placebo
Healthy subjects received a single dose of placebo administered SC
|
Sterile normal saline (0.9% NaCl) given by subcutaneous injection
|
EXPERIMENTAL: Part B: MAD VIR-2218 20 mg
Chronic HBV, HBeAg negative, subjects received 2 SC doses of 20 mg VIR-2218 administered 4 weeks apart.
|
VIR-2218 given by subcutaneous injection
|
EXPERIMENTAL: Part B: MAD VIR-2218 50 mg
Chronic HBV, HBeAg negative, subjects received 2 SC doses of 50 mg VIR-2218 administered 4 weeks apart.
|
VIR-2218 given by subcutaneous injection
|
EXPERIMENTAL: Part B: MAD VIR-2218 100 mg
Chronic HBV, HBeAg negative, subjects received 2 SC doses of 100 mg VIR-2218 administered 4 weeks apart.
|
VIR-2218 given by subcutaneous injection
|
EXPERIMENTAL: Part B: MAD VIR-2218 200 mg
Chronic HBV, HBeAg negative, subjects received 2 SC doses of 200 mg VIR-2218 administered 4 weeks apart.
|
VIR-2218 given by subcutaneous injection
|
EXPERIMENTAL: Part C: MAD VIR-2218 50 mg
Chronic HBV, HBeAg positive, subjects received 2 SC doses of 50 mg VIR-2218 administered 4 weeks apart.
|
VIR-2218 given by subcutaneous injection
|
EXPERIMENTAL: Part C: MAD VIR-2218 200 mg
Chronic HBV, HBeAg positive, subjects received 2 SC doses of 200 mg VIR-2218 administered 4 weeks apart.
|
VIR-2218 given by subcutaneous injection
|
PLACEBO_COMPARATOR: Part B: MAD Placebo
Chronic HBV, HBeAg negative, subjects received 2 SC doses of placebo administered 4 weeks apart.
|
Sterile normal saline (0.9% NaCl) given by subcutaneous injection
|
PLACEBO_COMPARATOR: Part C: MAD Placebo
Chronic HBV, HBeAg positive, subjects received 2 SC doses of placebo administered 4 weeks apart.
|
Sterile normal saline (0.9% NaCl) given by subcutaneous injection
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Incidence of Adverse Events (AEs)
Time Frame: Up to 364 days
|
Number of Subjects with Adverse Events as assessed by CTCAE v5.0.
In our planned analysis for this outcome measure, incidence is defined as the number of participants with treatment emergent AEs (TEAEs) in relation to the total number of participants in the cohort.
|
Up to 364 days
|
Clinical Assessments Including But Not Limited to Laboratory Test Results
Time Frame: Up to 336 days
|
Number of participants with clinically significant abnormalities in vital signs, electrocardiogram (ECG), and laboratory parameters graded by CTCAE v5.0.
|
Up to 336 days
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Maximum Plasma Concentration (ng/mL)
Time Frame: Part A: predose on Day 1 and at 30 min, 1h, 2h, 4h, 6h, 8h, 10h, 12h, 24h, 48h postdose and Week 1; Part B/C: predose on Day 1 and at 1h, 2h, 4h, 8h, 24h postdose, Week 1, predose on Week 4 and at 1h, 2h, 4h, 8h, 24h postdose, and Week 5
|
VIR-2218 and metabolite Maximum Concentration in Plasma
|
Part A: predose on Day 1 and at 30 min, 1h, 2h, 4h, 6h, 8h, 10h, 12h, 24h, 48h postdose and Week 1; Part B/C: predose on Day 1 and at 1h, 2h, 4h, 8h, 24h postdose, Week 1, predose on Week 4 and at 1h, 2h, 4h, 8h, 24h postdose, and Week 5
|
Time to Reach Maximum Plasma Concentration (h)
Time Frame: Part A: predose on Day 1 and at 30 min, 1h, 2h, 4h, 6h, 8h, 10h, 12h, 24h, 48h postdose and Week 1; Part B/C: predose on Day 1 and at 1h, 2h, 4h, 8h, 24h postdose, Week 1, predose on Week 4 and at 1h, 2h, 4h, 8h, 24h postdose, and Week 5
|
VIR-2218 and metabolite time of Cmax in Plasma: Median (Inter-Quartile Range Q1-Q3)
|
Part A: predose on Day 1 and at 30 min, 1h, 2h, 4h, 6h, 8h, 10h, 12h, 24h, 48h postdose and Week 1; Part B/C: predose on Day 1 and at 1h, 2h, 4h, 8h, 24h postdose, Week 1, predose on Week 4 and at 1h, 2h, 4h, 8h, 24h postdose, and Week 5
|
Area Under the Plasma Concentration Versus Time Curve (ng*h/mL)
Time Frame: Part A: predose on Day 1 and at 30 min, 1h, 2h, 4h, 6h, 8h, 10h, 12h, 24h, 48h postdose and Week 1; Part B/C: predose on Day 1 and at 1h, 2h, 4h, 8h, 24h postdose, Week 1, predose on Week 4 and at 1h, 2h, 4h, 8h, 24h postdose, and Week 5
|
VIR-2218 and metabolite Area under the curve from time 0 to last measurable Time
|
Part A: predose on Day 1 and at 30 min, 1h, 2h, 4h, 6h, 8h, 10h, 12h, 24h, 48h postdose and Week 1; Part B/C: predose on Day 1 and at 1h, 2h, 4h, 8h, 24h postdose, Week 1, predose on Week 4 and at 1h, 2h, 4h, 8h, 24h postdose, and Week 5
|
Apparent Terminal Elimination Half-life (h)
Time Frame: Part A: predose on Day 1 and at 30 min, 1h, 2h, 4h, 6h, 8h, 10h, 12h, 24h, 48h postdose and Week 1
|
VIR-2218 Apparent Elimination Half-life t1/2 in Plasma: Median (Inter-Quartile Range Q1-Q3)
|
Part A: predose on Day 1 and at 30 min, 1h, 2h, 4h, 6h, 8h, 10h, 12h, 24h, 48h postdose and Week 1
|
Apparent Plasma Clearance (L/h)
Time Frame: Part A: predose on Day 1 and at 30 min, 1h, 2h, 4h, 6h, 8h, 10h, 12h, 24h, 48h postdose, and Week 1
|
VIR-2218 CL/F Apparent plasma clearance
|
Part A: predose on Day 1 and at 30 min, 1h, 2h, 4h, 6h, 8h, 10h, 12h, 24h, 48h postdose, and Week 1
|
Apparent Volume of Distribution (L)
Time Frame: Part A: predose on Day 1 and at 30 min, 1h, 2h, 4h, 6h, 8h, 10h, 12h, 24h, 48h postdose, and Week 1
|
VIR-2218 VZ/F apparent volume of distribution
|
Part A: predose on Day 1 and at 30 min, 1h, 2h, 4h, 6h, 8h, 10h, 12h, 24h, 48h postdose, and Week 1
|
Urine %fe 0-24h
Time Frame: Pooled urine was collected at time interval D1 (0-4 hrs) (4-8 hrs) (8-12 hrs) and (12-24 hrs)
|
VIR-2218 and metabolite: Fraction excreted in the urine from time 0 to 24 h.
Pooled Urine PK samples was collected at pre-specified intervals in the single ascending dose study of VIR-2218.
Therefore, the following PK parameter, fraction excreted in the urine ( %fe 0-24h ) was only calculated in healthy subjects who participated in Part A of the study.
This parameter was not listed as a secondary endpoint for parts B/C in the submitted protocol, and as such was not reported in this secondary outcome measures.
|
Pooled urine was collected at time interval D1 (0-4 hrs) (4-8 hrs) (8-12 hrs) and (12-24 hrs)
|
Apparent Renal Clearance (CLR/F)
Time Frame: Pooled Urine was collected at time interval D1 (0-4 hrs) (4-8 hrs) (8-12 hrs) and (12-24 hrs)
|
VIR-2218 Apparent renal clearance from 0 to 24 h.
Pooled Urine PK samples was collected at pre-specified intervals in the single ascending dose study of VIR-2218.
Therefore, the following PK parameter, apparent renal clearance (CLR/F) was only calculated in healthy subjects who participated in Part A of the study.
This parameter was not listed as a secondary endpoint for parts B/C in the submitted protocol, and as such was not reported in this secondary outcome measures.
|
Pooled Urine was collected at time interval D1 (0-4 hrs) (4-8 hrs) (8-12 hrs) and (12-24 hrs)
|
Maximum Reduction of Serum HBsAg From Baseline
Time Frame: Up to 112 days
|
Maximum reduction of serum HBsAg from Day 1 until Week 16.
|
Up to 112 days
|
Number of Subjects With Serum HBsAg Loss at Any Time Point
Time Frame: Up to 336 days
|
Serum HBsAg loss is defined as quantitative HBsAg < 0.05 IU/mL at two or more consecutive measurements
|
Up to 336 days
|
Number of Subjects With Sustained Serum HBsAg Loss for >/= 6 Months
Time Frame: Up to 336 days
|
Serum HBsAg loss is defined as quantitative HBsAg < 0.05 IU/mL at two or more consecutive measurements
|
Up to 336 days
|
Number of Subjects With Anti-HBs Seroconversion at Any Timepoint
Time Frame: Up to 336 days
|
Anti-HBs seroconversion is defined as anti-HBs positivity at two or more consecutive measurements
|
Up to 336 days
|
Number of Subjects With HBeAg Loss and/or Anti-HBe Seroconversion at Any Timepoint
Time Frame: Up to 336 days
|
HBeAg loss is defined as quantitative HBeAg < 0.11 IU/mL at two or more consecutive measurements.
anti-HBe seroconversion is defined as anti-HBe positivity at two or more consecutive measurements
|
Up to 336 days
|
Collaborators and Investigators
Sponsor
Collaborators
Publications and helpful links
Study record dates
Study Major Dates
Study Start (ACTUAL)
Primary Completion (ACTUAL)
Study Completion (ACTUAL)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (ACTUAL)
Study Record Updates
Last Update Posted (ACTUAL)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Digestive System Diseases
- RNA Virus Infections
- Virus Diseases
- Infections
- Blood-Borne Infections
- Communicable Diseases
- Liver Diseases
- Hepatitis, Viral, Human
- Hepadnaviridae Infections
- DNA Virus Infections
- Enterovirus Infections
- Picornaviridae Infections
- Hepatitis B
- Hepatitis
- Hepatitis A
- Hepatitis B, Chronic
- Hepatitis, Chronic
Other Study ID Numbers
- VIR-2218-1001
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Chronic Hepatitis B
-
The Affiliated Nanjing Drum Tower Hospital of Nanjing...Gilead SciencesNot yet recruiting
-
Tongji HospitalGilead SciencesRecruiting
-
Jiangsu HengRui Medicine Co., Ltd.Unknown
-
Changhai HospitalCompleted
-
Zhongshan Hospital Xiamen UniversityUnknownHealthy | Chronic Hepatitis B InfectionChina
-
Tongji HospitalChia Tai Tianqing Pharmaceutical Group Co., Ltd.UnknownChronic Hepatitis b
-
Brii Biosciences LimitedVir Biotechnology, Inc.Active, not recruitingChronic Hepatitis B Virus InfectionSingapore, Thailand, Australia, China, Korea, Republic of
-
Nanfang Hospital of Southern Medical UniversityRecruiting
-
IlDong Pharmaceutical Co LtdRecruitingChronic Hepatitis bKorea, Republic of
-
Antios Therapeutics, IncTerminatedChronic Hepatitis bUnited States
Clinical Trials on VIR-2218
-
Vir Biotechnology, Inc.RecruitingA Study to Investigate the Effect of Renal Impairment on the Pharmacokinetics and Safety of VIR-2218Renal ImpairmentUnited States
-
Vir Biotechnology, Inc.RecruitingHepatitis D, ChronicNew Zealand, United Kingdom, Moldova, Republic of, Romania, Bulgaria, Italy, Germany, France, Netherlands
-
Vir Biotechnology, Inc.RecruitingCirrhosis | Hepatic ImpairmentUnited States
-
Vir Biotechnology, Inc.RecruitingHepatitis B, ChronicHong Kong, Korea, Republic of, Malaysia, New Zealand, Taiwan, United Kingdom, Romania, United States, Moldova, Republic of, Canada, Germany, Ukraine
-
Brii Biosciences LimitedAlnylam Pharmaceuticals; Vir Biotechnology, Inc.Completed
-
Vir Biotechnology, Inc.Active, not recruitingHepatitis B, ChronicHong Kong, Korea, Republic of, United Kingdom, France, Moldova, Republic of, Romania
-
Brii Biosciences LimitedVBI Vaccines Inc.; Vir Biotechnology, Inc.CompletedHepatitis B, ChronicAustralia, China, Korea, Republic of, New Zealand, Singapore, Thailand
-
National Institute of Diabetes and Digestive and...Not yet recruiting
-
Vir Biotechnology, Inc.Terminated