Study of VIR-2218 in Healthy Subjects and Patients With Chronic Hepatitis B

Chronic Hepatitis B Clinical Trial

Official title:

A Phase 1/2, Randomized, Placebo-Controlled Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Antiviral Activity of VIR-2218

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03672188
• Other study ID #: VIR-2218-1001
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: November 14, 2018
• Est. completion date: September 3, 2020

Study information

• Verified date: December 2021
• Source: Vir Biotechnology, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 82
• Est. completion date: September 3, 2020
• Est. primary completion date: September 3, 2020
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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

Related Conditions & MeSH terms

• Chronic Hepatitis B
• Hepatitis
• Hepatitis A
• Hepatitis B
• Hepatitis B, Chronic
• Hepatitis, Chronic

Intervention

Drug:
• VIR-2218
VIR-2218 given by subcutaneous injection
• Placebo
Sterile normal saline (0.9% NaCl) given by subcutaneous injection

Locations

Country	Name	City	State
Australia	Investigative Site	Birtinya	Queensland
Australia	Investigative Site	Clayton	Victoria
Australia	Investigative Site	Fitzroy	Victoria
Hong Kong	Investigative Site	Hong Kong
Korea, Republic of	Investigative Site	Busan
Korea, Republic of	Investigative Site	Seoul
Korea, Republic of	Investigative Site	Seoul
New Zealand	Investigative Site	Auckland
New Zealand	Investigative Site	Auckland
Thailand	Investigative Site	Bangkok
Thailand	Investigative Site	Bangkok
Thailand	Investigative Site	Bangkok
Thailand	Investigative Site	Hat Yai
Thailand	Investigative Site	Khon Kaen

Sponsors (2)

Lead Sponsor	Collaborator
Vir Biotechnology, Inc.	Alnylam Pharmaceuticals

Countries where clinical trial is conducted

Australia,  Hong Kong,  Korea, Republic of,  New Zealand,  Thailand, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of Adverse Events (AEs)	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
Primary	Clinical Assessments Including But Not Limited to Laboratory Test Results	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	Maximum Plasma Concentration (ng/mL)	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
Secondary	Time to Reach Maximum Plasma Concentration (h)	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
Secondary	Area Under the Plasma Concentration Versus Time Curve (ng*h/mL)	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
Secondary	Apparent Terminal Elimination Half-life (h)	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
Secondary	Apparent Plasma Clearance (L/h)	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
Secondary	Apparent Volume of Distribution (L)	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
Secondary	Urine %fe 0-24h	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)
Secondary	Apparent Renal Clearance (CLR/F)	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)
Secondary	Maximum Reduction of Serum HBsAg From Baseline	Maximum reduction of serum HBsAg from Day 1 until Week 16.	Up to 112 days
Secondary	Number of Subjects With Serum HBsAg Loss at Any Time Point	Serum HBsAg loss is defined as quantitative HBsAg < 0.05 IU/mL at two or more consecutive measurements	Up to 336 days
Secondary	Number of Subjects With Sustained Serum HBsAg Loss for >/= 6 Months	Serum HBsAg loss is defined as quantitative HBsAg < 0.05 IU/mL at two or more consecutive measurements	Up to 336 days
Secondary	Number of Subjects With Anti-HBs Seroconversion at Any Timepoint	Anti-HBs seroconversion is defined as anti-HBs positivity at two or more consecutive measurements	Up to 336 days
Secondary	Number of Subjects With HBeAg Loss and/or Anti-HBe Seroconversion at Any Timepoint	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