NCT03672188

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.

Trial Health

93
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
82

participants targeted

Target at P75+ for phase_1

Timeline
Completed

Started Nov 2018

Geographic Reach
5 countries

14 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

September 11, 2018

Completed
3 days until next milestone

First Posted

Study publicly available on registry

September 14, 2018

Completed
2 months until next milestone

Study Start

First participant enrolled

November 14, 2018

Completed
1.8 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

September 3, 2020

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

September 3, 2020

Completed
1.3 years until next milestone

Results Posted

Study results publicly available

December 13, 2021

Completed
Last Updated

December 13, 2021

Status Verified

December 1, 2021

Enrollment Period

1.8 years

First QC Date

September 11, 2018

Results QC Date

October 20, 2021

Last Update Submit

December 9, 2021

Conditions

Chronic Hepatitis B

Keywords

Hepatitis B VirusChronic Hepatitis BHBVHepatitis

Outcome Measures

Primary Outcomes (2)

  • 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

  • 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 Outcomes (13)

  • Maximum Plasma Concentration (ng/mL)

    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)

    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)

    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)

    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)

    Part A: predose on Day 1 and at 30 min, 1h, 2h, 4h, 6h, 8h, 10h, 12h, 24h, 48h postdose, and Week 1

  • +8 more secondary outcomes

Study Arms (15)

Part A: SAD VIR-2218 50 mg

EXPERIMENTAL

Healthy subjects received a single dose of VIR-2218 of 50 mg administered SC

Drug: VIR-2218

Part A: SAD VIR-2218 100 mg

EXPERIMENTAL

Healthy subjects received a single dose of VIR-2218 of 100 mg administered SC

Drug: VIR-2218

Part A: SAD VIR-2218 200 mg

EXPERIMENTAL

Healthy subjects received a single dose of VIR-2218 of 200 mg administered SC

Drug: VIR-2218

Part A: SAD VIR-2218 400 mg

EXPERIMENTAL

Healthy subjects received a single dose of VIR-2218 of 400 mg administered SC

Drug: VIR-2218

Part A: SAD VIR-2218 600 mg

EXPERIMENTAL

Healthy subjects received a single dose of VIR-2218 of 600 mg administered SC

Drug: VIR-2218

Part A: SAD VIR-2218 900 mg

EXPERIMENTAL

Healthy subjects received a single dose of VIR-2218 of 900 mg administered SC

Drug: VIR-2218

Part A: SAD Placebo

PLACEBO COMPARATOR

Healthy subjects received a single dose of placebo administered SC

Drug: Placebo

Part B: MAD VIR-2218 20 mg

EXPERIMENTAL

Chronic HBV, HBeAg negative, subjects received 2 SC doses of 20 mg VIR-2218 administered 4 weeks apart.

Drug: VIR-2218

Part B: MAD VIR-2218 50 mg

EXPERIMENTAL

Chronic HBV, HBeAg negative, subjects received 2 SC doses of 50 mg VIR-2218 administered 4 weeks apart.

Drug: VIR-2218

Part B: MAD VIR-2218 100 mg

EXPERIMENTAL

Chronic HBV, HBeAg negative, subjects received 2 SC doses of 100 mg VIR-2218 administered 4 weeks apart.

Drug: VIR-2218

Part B: MAD VIR-2218 200 mg

EXPERIMENTAL

Chronic HBV, HBeAg negative, subjects received 2 SC doses of 200 mg VIR-2218 administered 4 weeks apart.

Drug: VIR-2218

Part C: MAD VIR-2218 50 mg

EXPERIMENTAL

Chronic HBV, HBeAg positive, subjects received 2 SC doses of 50 mg VIR-2218 administered 4 weeks apart.

Drug: VIR-2218

Part C: MAD VIR-2218 200 mg

EXPERIMENTAL

Chronic HBV, HBeAg positive, subjects received 2 SC doses of 200 mg VIR-2218 administered 4 weeks apart.

Drug: VIR-2218

Part B: MAD Placebo

PLACEBO COMPARATOR

Chronic HBV, HBeAg negative, subjects received 2 SC doses of placebo administered 4 weeks apart.

Drug: Placebo

Part C: MAD Placebo

PLACEBO COMPARATOR

Chronic HBV, HBeAg positive, subjects received 2 SC doses of placebo administered 4 weeks apart.

Drug: Placebo

Interventions

VIR-2218DRUG

VIR-2218 given by subcutaneous injection

Part A: SAD VIR-2218 100 mgPart A: SAD VIR-2218 200 mgPart A: SAD VIR-2218 400 mgPart A: SAD VIR-2218 50 mgPart A: SAD VIR-2218 600 mgPart A: SAD VIR-2218 900 mgPart B: MAD VIR-2218 100 mgPart B: MAD VIR-2218 20 mgPart B: MAD VIR-2218 200 mgPart B: MAD VIR-2218 50 mgPart C: MAD VIR-2218 200 mgPart C: MAD VIR-2218 50 mg
PlaceboDRUG

Sterile normal saline (0.9% NaCl) given by subcutaneous injection

Part A: SAD PlaceboPart B: MAD PlaceboPart C: MAD Placebo

Eligibility Criteria

Age18 Years - 65 Years
Sexall
Healthy VolunteersYes
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Male or female age 18 - 55
  • BMI 18 - 32 kg/m\^2

You may not qualify if:

  • 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:
  • Male or female age 18 - 65
  • BMI 18 - 32 kg/m\^2
  • Chronic HBV infection for \>/= 6 months
  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (14)

Investigative Site

Birtinya, Queensland, 4575, Australia

Location

Investigative Site

Clayton, Victoria, 3168, Australia

Location

Investigative Site

Fitzroy, Victoria, 3065, Australia

Location

Investigative Site

Hong Kong, Hong Kong

Location

Investigative Site

Auckland, 1010, New Zealand

Location

Investigative Site

Auckland, 2025, New Zealand

Location

Investigative Site

Busan, 49241, South Korea

Location

Investigative Site

Seoul, 03080, South Korea

Location

Investigative Site

Seoul, 05505, South Korea

Location

Investigative Site

Bangkok, 10330, Thailand

Location

Investigative Site

Bangkok, 10400, Thailand

Location

Investigative Site

Bangkok, 10700, Thailand

Location

Investigative Site

Hat Yai, 90110, Thailand

Location

Investigative Site

Khon Kaen, 40002, Thailand

Location

Related Publications (3)

  • Yuen MF, Lim YS, Yoon KT, Lim TH, Heo J, Tangkijvanich P, Tak WY, Thanawala V, Cloutier D, Mao S, Arizpe A, Cathcart AL, Gupta SV, Hwang C, Gane E. VIR-2218 (elebsiran) plus pegylated interferon-alfa-2a in participants with chronic hepatitis B virus infection: a phase 2 study. Lancet Gastroenterol Hepatol. 2024 Dec;9(12):1121-1132. doi: 10.1016/S2468-1253(24)00237-1. Epub 2024 Oct 8.

    PMID: 39389081DERIVED

  • Gane E, Lim YS, Kim JB, Jadhav V, Shen L, Bakardjiev AI, Huang SA, Cathcart AL, Lempp FA, Janas MM, Cloutier DJ, Kaittanis C, Sepp-Lorenzino L, Hinkle G, Taubel J, Haslett P, Milstein S, Anglero-Rodriguez YI, Hebner CM, Pang PS, Yuen MF. Evaluation of RNAi therapeutics VIR-2218 and ALN-HBV for chronic hepatitis B: Results from randomized clinical trials. J Hepatol. 2023 Oct;79(4):924-932. doi: 10.1016/j.jhep.2023.05.023. Epub 2023 Jun 7.

    PMID: 37290591DERIVED

  • 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.

    PMID: 34741731DERIVED

MeSH Terms

Conditions

Hepatitis B, ChronicHepatitis BHepatitis

Condition Hierarchy (Ancestors)

Blood-Borne InfectionsCommunicable DiseasesInfectionsHepadnaviridae InfectionsDNA Virus InfectionsVirus DiseasesHepatitis, Viral, HumanHepatitis, ChronicLiver DiseasesDigestive System DiseasesChronic DiseaseDisease AttributesPathologic ProcessesPathological Conditions, Signs and Symptoms

Results Point of Contact

Title
Study Inquiry
Organization
Vir Biotechnology, Inc.
clinicaltrials@vir.bio
415-654-5281

Publication Agreements

PI is Sponsor Employee
No
Restriction Type
OTHER
Restrictive Agreement
Yes

Study Design

Study Type
interventional
Phase
phase 1
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

September 11, 2018

First Posted

September 14, 2018

Study Start

November 14, 2018

Primary Completion

September 3, 2020

Study Completion

September 3, 2020

Last Updated

December 13, 2021

Results First Posted

December 13, 2021

Record last verified: 2021-12

Locations

AU(3)NZ(2)KR(3)TH(5)HK(1)