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Chronic Hepatitis BPhase 1/2NCT03672188

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

A Phase 1/2 study testing VIR-2218 in people with Chronic Hepatitis B, run by Vir Biotechnology, Inc. at 14 sites in 5 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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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). Read more about this study

Who is it for?
Ages 18 to 65 yearsHealthy volunteers can take part
Conditions the study is for
Chronic Hepatitis B
What is being tested?
VIR-2218
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
82 participants
Where
14 sitesin 5 countries
Study dates
14 Nov 2018to 3 Sep 2020
Phase
Phase 1/2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 65 years
  • All sexes
  • Healthy volunteers accepted
  • Adult, Older adult

Who may be able to join

  • Male or female age 18 - 55
  • BMI 18 - 32 kg/m^2
  • Male or female age 18 - 65
  • BMI 18 - 32 kg/m^2
  • Chronic HBV infection for >/= 6 months

Who cannot join

  • 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:
  • Any clinically significant chronic or acute medical condition that makes the volunteer unsuitable for participation
  • Significant fibrosis or cirrhosis
Show all 10Show fewer
  • 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

Trial locations and contacts

14 sites in 5 countries.

14 sites in 5 countries

Thailand5 sites
  • Investigative Site

    Bangkok, 10330

  • Investigative Site

    Bangkok, 10400

  • Investigative Site

    Bangkok, 10700

  • Investigative Site

    Hat Yai, 90110

  • Investigative Site

    Khon Kaen, 40002

Other trials in Thailand

Australia3 sites
  • Investigative Site

    Birtinya, Queensland, 4575

  • Investigative Site

    Clayton, Victoria, 3168

  • Investigative Site

    Fitzroy, Victoria, 3065

Other trials in Australia

South Korea3 sites
  • Investigative Site

    Busan, 49241

  • Investigative Site

    Seoul, 03080

  • Investigative Site

    Seoul, 05505

Other trials in South Korea

New Zealand2 sites
  • Investigative Site

    Auckland, 1010

  • Investigative Site

    Auckland, 2025

Other trials in New Zealand

Hong Kong1 site
  • Investigative Site

    Hong Kong

Other trials in Hong Kong

About this study

Official title: 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.

Being tested
VIR-2218, Placebo
Keywords
Hepatitis B Virus, Chronic Hepatitis B, HBV, Hepatitis
Medical subject headings
Hepatitis B, Chronic, Hepatitis B, Hepatitis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • VIR-2218Drug

    VIR-2218 given by subcutaneous injection

  • PlaceboDrug

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

Study groups in NCT03672188
Study groupRoleWhat they receive
Part A: SAD VIR-2218 50 mgExperimentalHealthy subjects received a single dose of VIR-2218 of 50 mg administered SC
Receives: Drug: VIR-2218
Part A: SAD VIR-2218 100 mgExperimentalHealthy subjects received a single dose of VIR-2218 of 100 mg administered SC
Receives: Drug: VIR-2218
Part A: SAD VIR-2218 200 mgExperimentalHealthy subjects received a single dose of VIR-2218 of 200 mg administered SC
Receives: Drug: VIR-2218
Part A: SAD VIR-2218 400 mgExperimentalHealthy subjects received a single dose of VIR-2218 of 400 mg administered SC
Receives: Drug: VIR-2218
Part A: SAD VIR-2218 600 mgExperimentalHealthy subjects received a single dose of VIR-2218 of 600 mg administered SC
Receives: Drug: VIR-2218
Part A: SAD VIR-2218 900 mgExperimentalHealthy subjects received a single dose of VIR-2218 of 900 mg administered SC
Receives: Drug: VIR-2218
Part A: SAD PlaceboPlacebo comparatorHealthy subjects received a single dose of placebo administered SC
Receives: Drug: Placebo
Part B: MAD VIR-2218 20 mgExperimentalChronic HBV, HBeAg negative, subjects received 2 SC doses of 20 mg VIR-2218 administered 4 weeks apart.
Receives: Drug: VIR-2218
Part B: MAD VIR-2218 50 mgExperimentalChronic HBV, HBeAg negative, subjects received 2 SC doses of 50 mg VIR-2218 administered 4 weeks apart.
Receives: Drug: VIR-2218
Part B: MAD VIR-2218 100 mgExperimentalChronic HBV, HBeAg negative, subjects received 2 SC doses of 100 mg VIR-2218 administered 4 weeks apart.
Receives: Drug: VIR-2218
Part B: MAD VIR-2218 200 mgExperimentalChronic HBV, HBeAg negative, subjects received 2 SC doses of 200 mg VIR-2218 administered 4 weeks apart.
Receives: Drug: VIR-2218
Part C: MAD VIR-2218 50 mgExperimentalChronic HBV, HBeAg positive, subjects received 2 SC doses of 50 mg VIR-2218 administered 4 weeks apart.
Receives: Drug: VIR-2218
Part C: MAD VIR-2218 200 mgExperimentalChronic HBV, HBeAg positive, subjects received 2 SC doses of 200 mg VIR-2218 administered 4 weeks apart.
Receives: Drug: VIR-2218
Part B: MAD PlaceboPlacebo comparatorChronic HBV, HBeAg negative, subjects received 2 SC doses of placebo administered 4 weeks apart.
Receives: Drug: Placebo
Part C: MAD PlaceboPlacebo comparatorChronic HBV, HBeAg positive, subjects received 2 SC doses of placebo administered 4 weeks apart.
Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: Up to 364 days

  2. 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.

    Measured: Up to 336 days

Secondary outcomes (13)
  1. Maximum Plasma Concentration (ng/mL)

    VIR-2218 and metabolite Maximum Concentration in Plasma

    Measured: 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

  2. Time to Reach Maximum Plasma Concentration (h)

    VIR-2218 and metabolite time of Cmax in Plasma: Median (Inter-Quartile Range Q1-Q3)

    Measured: 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

  3. 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

    Measured: 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

  4. Apparent Terminal Elimination Half-life (h)

    VIR-2218 Apparent Elimination Half-life t1/2 in Plasma: Median (Inter-Quartile Range Q1-Q3)

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

  5. Apparent Plasma Clearance (L/h)

    VIR-2218 CL/F Apparent plasma clearance

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

  6. Apparent Volume of Distribution (L)

    VIR-2218 VZ/F apparent volume of distribution

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

  7. 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.

    Measured: Pooled urine was collected at time interval D1 (0-4 hrs) (4-8 hrs) (8-12 hrs) and (12-24 hrs)

  8. 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.

    Measured: Pooled Urine was collected at time interval D1 (0-4 hrs) (4-8 hrs) (8-12 hrs) and (12-24 hrs)

  9. Maximum Reduction of Serum HBsAg From Baseline

    Maximum reduction of serum HBsAg from Day 1 until Week 16.

    Measured: Up to 112 days

  10. 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

    Measured: Up to 336 days

  11. 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

    Measured: Up to 336 days

  12. 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

    Measured: Up to 336 days

  13. 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

    Measured: Up to 336 days

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted14 Sep 2018
  2. Study start14 Nov 2018
  3. Primary completion3 Sep 2020
  4. Study completion3 Sep 2020

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
82 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03672188
Sponsor's protocol ID
VIR-2218-1001
Status last verified
Dec 2021
First submitted
11 Sep 2018
Last updated
13 Dec 2021
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • 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.

    PubMed 39389081
  • 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.

    PubMed 37290591
  • 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.

    PubMed 34741731

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing VIR-2218 in people with Chronic Hepatitis B, run by Vir Biotechnology, Inc. at 14 sites in 5 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 13 Dec 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 14 sites in Thailand, Australia, South Korea, New Zealand, Hong Kong. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 13 Dec 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Incidence of Adverse Events (AEs) (time frame: Up to 364 days). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03672188, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Dec 2021.

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