Trial reportPLoS medicine2024
Safety and tolerability of tegoprubart in patients with amyotrophic lateral sclerosis: A Phase 2A clinical trial.
Trial report in PLoS medicine, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04322149 (A Phase 2a Open-Label, Multi-Center Study to Evaluate the Safety and Tolerability of Multiple Doses of AT-1501 in Adults With ALS), which is not on this map. Cited by 8 papers.
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 2a Open-Label, Multi-Center Study to Evaluate the Safety and Tolerability of Multiple Doses of AT-1501 in Adults With ALS
Who cites it
8 citing papers in PubMed.
- Bridging the gap: neuroinflammation and the dawn of precision medicine in amyotrophic lateral sclerosis.Translational neurodegeneration · 2026Review
- Effect of Immunosuppressive Drugs on Glucose-Stimulated Insulin Secretion: Concentration-Response Studies in Dynamic Perifusion Assays.bioRxiv : the preprint server for biology · 2026Article
- The CD40-CD154 axis in transplantation: from immunobiology to therapeutic targeting.Frontiers in immunology · 2026Review
- Therapeutic Challenges and Future Breakthroughs in Amyotrophic Lateral Sclerosis: From Precision Medicine to Innovative Trial Design.Drug design, development and therapy · 2026Review
- Cutting-edge treatments in amyotrophic lateral sclerosis: the role of molecular pathogenesis in targeted therapies.Stem cell research & therapy · 2025Review
- Review
- TDP-43 pathology induces CD8bioRxiv : the preprint server for biology · 2025Article
- Immunosuppressive and Non-Immunosuppressive Drugs for Heart Xenotransplantation in Humans: Is Europe Ready?XenotransplantationReview
Corrections and comments
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Authors and funding
16 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe interaction of CD40L and its receptor CD40 on activated T cells and B cells respectively control pro-inflammatory activation in the pathophysiology of autoimmunity and transplant rejection. Previous studies have implicated signaling pathways involving CD40L (interchangeably referred to as CD154), as well as adaptive and innate immune cell activation, in the induction of neuroinflammation in neurodegenerative diseases. This study aimed to assess the safety, tolerability, and impact on pro-inflammatory biomarker profiles of an anti CD40L antibody, tegoprubart, in individuals with amyotrophic lateral sclerosis (ALS). METHODS AND
findingsIn this multicenter dose-escalating open-label Phase 2A study, 54 participants with a diagnosis of ALS received 6 infusions of tegoprubart administered intravenously every 2 weeks. The study was comprised of 4 dose cohorts: 1 mg/kg, 2 mg/kg, 4 mg/kg, and 8 mg/kg. The primary endpoint of the study was safety and tolerability. Exploratory endpoints assessed the pharmacokinetics of tegoprubart as well as anti-drug antibody (ADA) responses, changes in disease progression utilizing the Revised ALS Functional Rating Scale (ALSFRS-R), CD154 target engagement, changes in pro-inflammatory biomarkers, and neurofilament light chain (NFL). Seventy subjects were screened, and 54 subjects were enrolled in the study. Forty-nine of 54 subjects completed the study (90.7%) receiving all 6 infusions of tegoprubart and completing their final follow-up visit. The most common treatment emergent adverse events (TEAEs) overall (>10%) were fatigue (25.9%), falls (22.2%), headaches (20.4%), and muscle spasms (11.1%). Mean tegoprubart plasma concentrations increased proportionally with increasing dose with a half-life of approximately 24 days. ADA titers were low and circulating levels of tegoprubart were as predicted for all cohorts. Tegoprubart demonstrated dose dependent target engagement associated and a reduction in 18 pro-inflammatory biomarkers in circulation.
conclusionsTegoprubart appeared to be safe and well tolerated in adults with ALS demonstrating dose-dependent reduction in pro-inflammatory chemokines and cytokines associated with ALS. These results warrant further clinical studies with sufficient power and duration to assess clinical outcomes as a potential treatment for adults with ALS.
trial registrationClintrials.gov ID:NCT04322149.
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