Trial reportTransplantation2017
Blockade of HLA Antibody-Triggered Classical Complement Activation in Sera From Subjects Dosed With the Anti-C1s Monoclonal Antibody TNT009-Results from a Randomized First-in-Human Phase 1 Trial.
Trial report in Transplantation, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers, 1 of them a synthesis 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
12 citing papers in PubMed, 1 synthesis or guideline pooled it, 29 citations in OpenAlex.
- Systematic review of basket trials, umbrella trials, and platform trials: a landscape analysis of master protocols.Trials · 2019Pooled it
- Complement in Antibody-Mediated Rejection of the Kidney Graft: From Pathophysiology to Clinical Practice.Journal of clinical medicine · 2025Review
- Torque Teno Virus Control by the Classical Pathway of Complement Activation-A Retrospective Analysis From a First-in-Human Trial Utilizing Sutimlimab.Journal of medical virology · 2024Article
- Sutimlimab for the Treatment of Cold Agglutinin Disease.HemaSphere · 2023Review
- Sutimlimab: First Approval.Drugs · 2022Review
- Pemphigus and Pemphigoid: From Disease Mechanisms to Druggable Pathways.The Journal of investigative dermatology · 2022Review
- B Cell Immunity in Lung Transplant Rejection - Effector Mechanisms and Therapeutic Implications.Frontiers in immunology · 2022Review
- Complement C1s as a diagnostic marker and therapeutic target: Progress and propective.Frontiers in immunology · 2022Review
- Aberrant activation of the complement system in renal grafts is mediated by cold storage.American journal of physiology. Renal physiology · 2021Article
- An overview of precision oncology basket and umbrella trials for clinicians.CA: a cancer journal for clinicians · 2020Review
- The therapeutic challenge of late antibody-mediated kidney allograft rejection.Transplant international : official journal of the European Society for Organ Transplantation · 2019Review
- Complement Activation in Autoimmune Bullous Dermatoses: A Comprehensive Review.Frontiers in immunology · 2019Review
Corrections and comments
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Authors and funding
11 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundComplement may play a key role in antibody-mediated rejection. A promising therapeutic approach may be classical pathway (CP) inhibition at the level of early component C1.
methodsIn this first-in-human, double-blind, randomized placebo-controlled phase 1 trial, we evaluated the safety and complement inhibitory effect of TNT009, a humanized monoclonal anti-C1s antibody. Sixty-four adult healthy volunteers received either single (n = 48; 7 consecutive cohorts, 0.3-100 mg/kg) or 4 weekly infusions (n = 16; 2 consecutive cohorts, 30 and 60 mg/kg per infusion) of TNT009 or placebo. To assess the effect of treatment on complement activity, sera from dosed subjects were analyzed in a CP activation assay evaluating C3d deposition on HLA-coated microbeads spiked with alloantibodies.
resultsSingle doses of TNT009 at 3 to 100 mg/kg uniformly and profoundly inhibited HLA antibody-mediated C3d deposition (≥86% after 60 minutes), whereby the duration of CP inhibition (2-14 days) was dose-dependent. Four weekly doses persistently blocked complement for 5 to 6 weeks. Ex vivo serum CP activity was profoundly inhibited when TNT009 concentrations exceeded 20 μg/mL. Infusions were well tolerated without serious or severe adverse events.
conclusionsTreatment with TNT009 was safe and potently inhibited CP activity. Future studies in patients are required to assess the potential of TNT009 for preventing or treating antibody-mediated rejection.
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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.