Trial reportAntimicrobial agents and chemotherapy2013
Characterization of Hepatitis C virus resistance from a multiple-dose clinical trial of the novel NS5A inhibitor GS-5885.
Trial report in Antimicrobial agents and chemotherapy, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01193478 (A Phase 1, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Antiviral Activity of Escalating, Multiple, Oral Doses of GS 5885 in Treatment Naïve Subjects With Chronic Genotype 1 Hepatitis C Virus Infection), which is not on this map. Cited by 36 papers, 2 of them syntheses that pooled it.
What it found
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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.
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.
A Phase 1, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Antiviral Activity of Escalating, Multiple, Oral Doses of GS 5885 in Treatment Naïve Subjects With Chronic Genotype 1 Hepatitis C Virus Infection
Who cites it
36 citing papers in PubMed, 2 syntheses or guidelines pooled it, 95 citations in OpenAlex.
- SASLT guidelines: Update in treatment of Hepatitis C virus infection.Saudi journal of gastroenterology : official journal of the Saudi Gastroenterology Association · 2016Guideline
- Hepatitis C virus genotype 3: Meta-analysis on sustained virologic response rates with currently available treatment options.World journal of gastroenterology · 2016Pooled it
- Trial
- Preclinical Profile and Clinical Efficacy of a Novel Hepatitis C Virus NS5A Inhibitor, EDP-239.Antimicrobial agents and chemotherapy · 2016Trial
- Preclinical and Clinical Resistance Profile of EDP-239, a Novel Hepatitis C Virus NS5A Inhibitor.Antimicrobial agents and chemotherapy · 2016Trial
- Clinical Resistance to Velpatasvir (GS-5816), a Novel Pan-Genotypic Inhibitor of the Hepatitis C Virus NS5A Protein.Antimicrobial agents and chemotherapy · 2016Trial
- Analysis of Hepatitis C Virus Genotype 1b Resistance Variants in Japanese Patients Treated with Paritaprevir-Ritonavir and Ombitasvir.Antimicrobial agents and chemotherapy · 2016Trial
- Successful Retreatment of Chronic HCV Genotype-1 Infection With Ledipasvir and Sofosbuvir After Initial Short Course Therapy With Direct-Acting Antiviral Regimens.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2016Trial
- Potent Antiviral Activities of the Direct-Acting Antivirals ABT-493 and ABT-530 with Three-Day Monotherapy for Hepatitis C Virus Genotype 1 Infection.Antimicrobial agents and chemotherapy · 2015Trial
- Infrequent development of resistance in genotype 1-6 hepatitis C virus-infected subjects treated with sofosbuvir in phase 2 and 3 clinical trials.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2014Trial
- Article
- NS5A-P32 deletion as a factor involved in virologic failure in patients receiving glecaprevir and pibrentasvir.Journal of gastroenterology · 2019Article
- Association Between Baseline Creatinine Clearance and Treatment Failure in Patients With Hepatitis C Virus Treated With Ledipasvir and Sofosbuvir.Open forum infectious diseases · 2019Article
- Resistance detection and re-treatment options in hepatitis C virus-related chronic liver diseases after DAA-treatment failure.Infection · 2018Review
- Hepatitis C Guidance 2018 Update: AASLD-IDSA Recommendations for Testing, Managing, and Treating Hepatitis C Virus Infection.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2018Article
- Article
- The global origins of resistance-associated variants in the non-structural proteins 5A and 5B of the hepatitis C virus.Virus evolution · 2018Article
- Sofosbuvir (SOF) Suppresses Ledipasvir (LDV)-resistant Mutants during SOF/LDV Combination Therapy against Genotype 1b Hepatitis C Virus (HCV).Scientific reports · 2017Article
- Retreatment with sofosbuvir, ledipasvir, and add-on ribavirin for patients who failed daclatasvir and asunaprevir combination therapy.Journal of gastroenterology · 2017Article
- Hepatitis C Virus-Genotype 3: Update on Current and Emergent Therapeutic Interventions.Current infectious disease reports · 2017Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
GS-5885 is a novel hepatitis C virus (HCV) NS5A inhibitor. In a 3-day monotherapy study in treatment-naive genotype 1a (GT1a) and GT1b HCV-infected subjects, median viral load reductions ranged from 2.3 to 3.3 log10 HCV RNA IU/ml across dosing cohorts (1, 3, 10, 30, or 90 mg once daily). Here, we report viral sequencing and phenotypic analysis of clinical isolates from this study. Detection of baseline NS5A amino acid substitutions at positions 28, 30, 31, or 93 in GT1a was associated with a reduced treatment response. In the GT1b cohort, Y93H was detected in 100% of subjects at day 4 or 14. In the Gt1a cohort, population sequencing detected NS5A resistance-associated mutations at day 4 or 14 for 3/10 subjects at the 1-mg dose and for all subjects dosed at ≥3 mg. A subset of mutants that confer a low level of reduced susceptibility to GS-5885 was not detected by population sequencing at the 30- and 90-mg doses. Subject-derived M28T, Q30R, L31M, and Y93C mutations all conferred >30-fold reductions in GS-5885 and daclatasvir susceptibilities in vitro. Site-directed NS5A mutants also showed reduced susceptibility to GS-5885. However, all NS5A mutants tested remained fully susceptible to other classes of direct-acting antivirals (DAAs), interferon alpha, and ribavirin. Importantly, the nonoverlapping resistance profile and high potency of GS-5885 support its further development with other direct-acting antivirals for the treatment of chronic HCV. (This study has been registered at ClinicalTrials.gov under registration number NCT01193478.).
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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.