Evidence map›Paper›PMID 40409326›Full record

ArticleThe lancet. HIV2025

Safety and pharmacokinetics of N6LS, a broadly neutralising monoclonal antibody for HIV: a phase 1, open-label, dose-escalation study in healthy adults.

Richard L Wu, Katherine V Houser, Martin R Gaudinski, Alicia T Widge, Seemal F Awan, Cristina A Carter, LaSonji A Holman, Jamie Saunders, Cynthia S Hendel, Aba Eshun and 41 more

Registry-linked trialAbstract readClinical Trial, Phase I
PubMed Full text at PMC Publisher
In one paragraph

Article in The lancet. HIV, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03538626 (VRC 609), which is not on this map. Cited by 7 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed, 1 pooled it
–field-weighted citation impact
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.

NCT03538626 phase1completednot on this map

VRC 609: A Phase I, Open-Label, Dose-Escalation Study of the Safety and Pharmacokinetics of a Human Monoclonal Antibody, VRC-HIVMAB091-00-AB (N6LS), Administered Intravenously or Subcutaneously With or Without Recombinant Human Hyaluronidase PH20 (rHuPH20) to Healthy Adults

TypeinterventionalSponsorNational Institute of Allergy and Infectious Diseases (NIAID)Ran2018 to 2022Enrolled33ConditionsHIV AntibodiesArmsVRC-HIVMAB091-00-AB, rHuPH20
3 · Its place in the literature

Who cites it

7 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Article
  3. Article
  4. Article
  5. Review
  6. Review
  7. Article
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

51 authors.

Richard L WuVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA; US Public Health Service Commissioned Corps, Rockville, MD, USA.
Katherine V HouserVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA. Electronic address: katherine.houser@nih.gov.
Martin R GaudinskiVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA; US Public Health Service Commissioned Corps, Rockville, MD, USA.
Alicia T WidgeVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
Seemal F AwanVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
Cristina A CarterVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
LaSonji A HolmanVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
Jamie SaundersVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
Cynthia S HendelVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
Aba EshunVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
William R WhalenVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
Xiaolin WangVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
Anita ArthurVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
Jennifer E CunninghamVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
Allison BeckVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
Joseph P CasazzaVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
Galina V YamshchikovVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
Ro Shauna RothwellVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
Larisa StromVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
Tejaswi DittakaviVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
Myra HappeVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
Somia P HickmanVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
Michelle Conan-CibottiVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
Kevin CarltonVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
Lily ZhangFred Hutchinson Cancer Research Center, Seattle, WA, USA.
Yunda HuangFred Hutchinson Cancer Research Center, Seattle, WA, USA.
Edmund V CapparelliSchool of Medicine and Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, San Diego, CA, USA.
Mike CastroVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
Bob C LinVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
Sarah O'ConnellVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
Britta S FlachVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
Robert T BailerVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
Sandeep R NarpalaVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
Leonid SerebryannyyVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
Adrian B McDermottVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
Frank J ArnoldVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
Jason G GallVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
Sandra VazquezVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
Nina M BerkowitzVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
Ingelise J GordonVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
Grace L ChenVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
Peter D KwongVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
Jinghe HuangHIV-Specific Immunity Section, Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
Theodore C PiersonVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
Mark ConnorsHIV-Specific Immunity Section, Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
John R MascolaVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
Tongqing ZhouVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
Nicole A Doria-RoseVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
Richard A KoupVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
Lesia K DropulicVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
VRC 609 study team

Funding

Intramural NIH HHS Z99 AI999999
6 · The paper itself

Abstract

backgroundBroadly neutralising antibodies (bNAbs) have shown promise as both prevention and treatment strategies against HIV-1. The clinical effectiveness of bNAbs depends on enhancing their neutralisation breadth and extending their serum half-lives. In this study, we aimed to assess the safety, tolerability, pharmacokinetic profile, and neutralisation activity in serum of N6LS, a HIV-1 bNAb.

methodsIn this first-in-human, dose-escalation, open-label, phase 1 trial, healthy adult participants (aged 18-50 years) who were HIV-1 negative were recruited to the National Institutes of Health Clinical Center (Bethesda, MD, USA). Three groups received one intravenous administration of N6LS at 5 mg/kg (n=3), 20 mg/kg (n=3), or 40 mg/kg (n=3); one group received one subcutaneous administration of 5 mg/kg N6LS (n=3); two groups received three administrations of either 5 mg/kg subcutaneous (n=5) or 20 mg/kg intravenous (n=5) N6LS every 12 weeks; and two groups received one subcutaneous administration of either 5 mg/kg (n=5) or 20 mg/kg (n=5) N6LS with ENHANZE drug product (EDP), recombinant human hyaluronidase PH20. The primary objectives were the safety and tolerability of N6LS with and without EDP. All participants who received N6LS were included in the primary safety analyses. This trial is registered at ClinicalTrials.gov, NCT03538626, and is complete.

findingsBetween June 18, 2018, and April 11, 2022, we enrolled 33 healthy adults (19 female individuals and 14 male individuals). One participant did not receive N6LS and one participant was lost to follow-up after 8 weeks. N6LS had an encouraging safety profile similar to other HIV-1 bNAbs, with no serious adverse events. Local reactogenicity was observed after administration of N6LS, with the most common symptom being mild to moderate injection site pain or tenderness in subcutaneous groups, reported in six of eight participants. All ten participants who received N6LS with EDP had mild to severe injection site erythema, which, despite being graded as severe in size, was generally not noticed by participants or deemed bothersome, and resolved without intervention. Systemic reactogenicity was mild in all groups. N6LS had an overall mean serum half-life of 48·6 days and retained its broad and potent neutralisation characteristics in serum. EDP administration increased N6LS bioavailability. No functional anti-drug antibodies to N6LS were detected following administration.

interpretationN6LS showed a promising safety and pharmacokinetics profile while retaining its potent neutralisation characteristics in serum, making it a promising candidate for inclusion in HIV-1 prevention and therapeutic combination strategies. The addition of EDP can enable safe subcutaneous administration of higher doses and larger volumes of N6LS, supporting additional methods for prophylactic and therapeutic bNAb administration.

fundingUS National Institute of Allergy and Infectious Diseases Intramural Research Program, National Institutes of Health.

Indexed as

Antibodies, MonoclonalAntibodies, NeutralizingBroadly Neutralizing AntibodiesHIV-1HIV AntibodiesHIV InfectionsAdolescentAdultFemaleHealthy VolunteersHumansInjections, SubcutaneousMaleMiddle AgedYoung AdultAntibodies, MonoclonalAntibodies, NeutralizingBroadly Neutralizing AntibodiesHIV Antibodies

Identifiers

PMID40409326
PMCPMC12282510

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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.