Evidence map›Paper›PMID 34741731›Full record

Trial reportDrugs in R&D2021

Clinical and Preclinical Single-Dose Pharmacokinetics of VIR-2218, an RNAi Therapeutic Targeting HBV Infection.

Sneha V Gupta, Marie C Fanget, Christopher MacLauchlin, Valerie A Clausen, Jing Li, Daniel Cloutier, Ling Shen, Gabriel J Robbie, Erik Mogalian

Registry-linked trialOpen access · goldAbstract readRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Drugs in R&D, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03672188 (A Phase 1/2, Randomized, Placebo-Controlled Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Antiviral Activity of VIR-2218), which is not on this map. Cited by 16 papers.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed
3.0field-weighted citation impact, top 8% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT03672188 phase1 / phase2completednot on this map

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

TypeinterventionalSponsorVir Biotechnology, Inc.Ran2018 to 2020Enrolled82ConditionsChronic Hepatitis BArmsVIR-2218, Placebo
3 · Its place in the literature

Who cites it

16 citing papers in PubMed, 28 citations in OpenAlex.

  1. Review
  2. Article
  3. Review
  4. Review
  5. Review
  6. Review
  7. Nucleic acid drugs: recent progress and future perspectives.Signal transduction and targeted therapy · 2024
    Review
  8. Review
  9. Article
  10. Article
  11. Review
  12. Review
  13. Review
  14. Review
  15. Potential of siRNA in COVID-19 therapy: Emphasis onFrontiers in bioengineering and biotechnology · 2023
    Review
  16. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors at 2 institutions in 1 country.

Sneha V GuptaClinical Pharmacology, Vir Biotechnology, Inc., San Francisco, CA, USA. sgupta@vir.bio.
Marie C FangetBioanalytical Sciences, Vir Biotechnology, Inc., San Francisco, CA, USA.
Christopher MacLauchlinDrug Metabolism and Pharmacokinetics, Alnylam Pharmaceuticals, Inc., Cambridge, MA, USA.
Valerie A ClausenBioanalytical Sciences, Alnylam Pharmaceuticals, Inc., Cambridge, MA, USA.
Jing LiBioanalytical Sciences, Alnylam Pharmaceuticals, Inc., Cambridge, MA, USA.
Daniel CloutierClinical Research, Vir Biotechnology, Inc., San Francisco, CA, USA.
Ling ShenBiometrics, Vir Biotechnology, Inc., San Francisco, CA, USA.
Gabriel J RobbieClinical Pharmacology and Pharmacometrics, Alnylam Pharmaceuticals, Inc., Cambridge, MA, USA.
Erik MogalianClinical Pharmacology, Vir Biotechnology, Inc., San Francisco, CA, USA.
VIR Biotechnology (United States) · USAlnylam Pharmaceuticals (United States) · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

BACKGROUND AND

objectiveVIR-2218 is an investigational N-acetylgalactosamine-conjugated RNA interference therapeutic in development for chronic hepatitis B virus (HBV) infection. VIR-2218 was designed to silence HBV transcripts across all genotypes and uses Enhanced Stabilization Chemistry Plus (ESC+) technology. This study was designed to evaluate the single-dose pharmacokinetics of VIR-2218 in preclinical species and healthy volunteers.

methodsPreclinically, a single subcutaneous dose of VIR-2218 (10 mg/kg) was administered to rats and nonhuman primates (NHPs), and the pharmacokinetics were assessed in plasma, urine, and liver using standard noncompartmental analysis (NCA) methods. Clinically, healthy volunteers were randomized (6:2 active:placebo) to receive a single subcutaneous dose of VIR-2218 (50-900 mg) or placebo. Pharmacokinetics were similarly assessed within human plasma and urine using NCA methods.

resultsIn rats and NHPs, VIR-2218 was stable in plasma and was converted to AS(N-1)3'VIR-2218, the most prominent circulating metabolite, at < 10% plasma exposure compared with parent. VIR-2218 rapidly distributed to the liver, reaching peak liver concentrations within 7 and 24 h in rats and NHPs, respectively. In humans, VIR-2218 was rapidly absorbed, with a median time to peak plasma concentration (t

conclusionsVIR-2218 showed favorable pharmacokinetics in healthy volunteers supportive of subcutaneous dosing and continued development in patients with chronic HBV infection. CLINICAL TRIAL REGISTRATION NO: NCT03672188, September 14, 2018.

Indexed as

Hepatitis B, ChronicHepatitis B virusAnimalsArea Under CurveHumansRatsRNA InterferenceRNAi Therapeutics

Identifiers

PMID34741731
PMCPMC8602582
OpenAlexW3214592746

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
Read underepoch 390

Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.