Clinical trial NCT03672188: Study of VIR-2218 in Healthy Subjects and Patients With Chronic Hepatitis B
Official title: A Phase 1/2, Randomized, Placebo-Controlled Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Antiviral Activity of VIR-2218
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Chronic Hepatitis B
Keywords: Hepatitis B Virus
Chronic Hepatitis B
HBV
Hepatitis
Lead sponsor: Vir Biotechnology, Inc.
Sponsor class: INDUSTRY
Collaborators: name: Alnylam Pharmaceuticals
First posted: 2018-09-14
Enrollment: 82
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: 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.


Eligibility criteria: 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

Primary outcomes:
measure: Incidence of Adverse Events (AEs)
timeFrame: Up to 364 days
measure: Clinical Assessments Including But Not Limited to Laboratory Test Results
timeFrame: Up to 336 days
Secondary outcomes:
measure: Maximum Plasma Concentration (ng/mL)
timeFrame: 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
measure: Time to Reach Maximum Plasma Concentration (h)
timeFrame: 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
measure: Area Under the Plasma Concentration Versus Time Curve (ng*h/mL)
timeFrame: 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
measure: Apparent Terminal Elimination Half-life (h)
timeFrame: Part A: predose on Day 1 and at 30 min, 1h, 2h, 4h, 6h, 8h, 10h, 12h, 24h, 48h postdose and Week 1
measure: Apparent Plasma Clearance (L/h)
timeFrame: Part A: predose on Day 1 and at 30 min, 1h, 2h, 4h, 6h, 8h, 10h, 12h, 24h, 48h postdose, and Week 1
measure: Apparent Volume of Distribution (L)
timeFrame: Part A: predose on Day 1 and at 30 min, 1h, 2h, 4h, 6h, 8h, 10h, 12h, 24h, 48h postdose, and Week 1
measure: Urine %fe 0-24h
timeFrame: Pooled urine was collected at time interval D1 (0-4 hrs) (4-8 hrs) (8-12 hrs) and (12-24 hrs)
measure: Apparent Renal Clearance (CLR/F)
timeFrame: Pooled Urine was collected at time interval D1 (0-4 hrs) (4-8 hrs) (8-12 hrs) and (12-24 hrs)
measure: Maximum Reduction of Serum HBsAg From Baseline
timeFrame: Up to 112 days
measure: Number of Subjects With Serum HBsAg Loss at Any Time Point
timeFrame: Up to 336 days
measure: Number of Subjects With Sustained Serum HBsAg Loss for >/= 6 Months
timeFrame: Up to 336 days
measure: Number of Subjects With Anti-HBs Seroconversion at Any Timepoint
timeFrame: Up to 336 days
measure: Number of Subjects With HBeAg Loss and/or Anti-HBe Seroconversion at Any Timepoint
timeFrame: Up to 336 days
Other outcomes:
Locations:
city: Birtinya
country: Australia
facility: Investigative Site
state: Queensland
city: Clayton
country: Australia
facility: Investigative Site
state: Victoria
city: Fitzroy
country: Australia
facility: Investigative Site
state: Victoria
city: Hong Kong
country: Hong Kong
facility: Investigative Site
city: Busan
country: Korea, Republic of
facility: Investigative Site
city: Seoul
country: Korea, Republic of
facility: Investigative Site
city: Seoul
country: Korea, Republic of
facility: Investigative Site
city: Auckland
country: New Zealand
facility: Investigative Site
city: Auckland
country: New Zealand
facility: Investigative Site
city: Bangkok
country: Thailand
facility: Investigative Site
city: Bangkok
country: Thailand
facility: Investigative Site
city: Bangkok
country: Thailand
facility: Investigative Site
city: Hat Yai
country: Thailand
facility: Investigative Site
city: Khon Kaen
country: Thailand
facility: Investigative Site
Study officials:
References:
citation: Gupta SV, Fanget MC, MacLauchlin C, Clausen VA, Li J, Cloutier D, Shen L, Robbie GJ, Mogalian E. Clinical and Preclinical Single-Dose Pharmacokinetics of VIR-2218, an RNAi Therapeutic Targeting HBV Infection. Drugs R D. 2021 Dec;21(4):455-465. doi: 10.1007/s40268-021-00369-w. Epub 2021 Nov 6.