Trial reportClinical pharmacology in drug development2020
First-in-Human Study of AG10, a Novel, Oral, Specific, Selective, and Potent Transthyretin Stabilizer for the Treatment of Transthyretin Amyloidosis: A Phase 1 Safety, Tolerability, Pharmacokinetic, and Pharmacodynamic Study in Healthy Adult Volunteers.
Trial report in Clinical pharmacology in drug development, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
29 citing papers in PubMed, 61 citations in OpenAlex.
- Specific treatment of ATTR-CM in Germany-expert consensus of the German Society of Amyloid Diseases (DGAK) and German Cardiac Society (DGK).Clinical research in cardiology : official journal of the German Cardiac Society · 2026Review
- Transthyretin at the crossroads of neurodegeneration: a silent guardian in Parkinson's disease.Metabolic brain disease · 2026Review
- Transthyretin Amyloidosis-From Peculiar Neuropathy to a Treatable Chronic Multisystemic Disease.Genes · 2026Review
- Differential Transthyretin Stabilization in Patients With Wild Type and Variant Transthyretin Amyloidosis.JACC. CardioOncology · 2026Article
- Efficacy of Acoramidis in Adults With Transthyretin Amyloid Cardiomyopathy: Propensity Score Comparison Between a Single-Arm Open-Label Phase 3 Trial in Japan and a Global Double-Blind Phase 3 Trial.Circulation reports · 2026Article
- Acoramidis in transthyretin amyloid cardiomyopathy: expanding evidence from ATTRibute-CM.Future cardiology · 2026Review
- Investigation of Acoramidis-based ionic liquids as potential stabilizers of transthyretin using DFT calculations, molecular docking, and ADMET studies.Scientific reports · 2026Article
- Transthyretin amyloid cardiomyopathy: from cause to novel treatments.European heart journal · 2026Review
- Transthyretin Kinetic Stabilizers for ATTR Amyloidosis: A Narrative Review of Mechanisms and Therapeutic Benefits.Cardiology and therapy · 2025Review
- Disease-modifying therapies for amyloid transthyretin cardiomyopathy: Current and emerging medications.Pharmacotherapy · 2025Review
- Cardiac amyloidosis: Innovations in diagnosis and treatment.European heart journal supplements : journal of the European Society of Cardiology · 2025Article
- From Molecular to Radionuclide and Pharmacological Aspects in Transthyretin Cardiac Amyloidosis.International journal of molecular sciences · 2024Review
- Evolution of Disease-modifying Therapy for Transthyretin Cardiac Amyloidosis.Heart international · 2024Review
- A Comprehensive Review on Chemistry and Biology of Tafamidis in Transthyretin Amyloidosis.Mini reviews in medicinal chemistry · 2024Review
- Tafamidis polyneuropathy amelioration requires modest increases in transthyretin stability even though increases in plasma native TTR and decreases in non-native TTR do not predict response.Amyloid : the international journal of experimental and clinical investigation : the official journal of the International Society of Amyloidosis · 2023Article
- Drug and Gene Therapy for Treating Variant Transthyretin Amyloidosis (ATTRv) Neuropathy.Current neuropharmacology · 2023Article
- Oral Therapy for the Treatment of Transthyretin-Related Amyloid Cardiomyopathy.International journal of molecular sciences · 2022Review
- Hereditary transthyretin amyloidosis overview.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2022Review
- Cardiac Amyloidosis.Heart failure clinics · 2022Review
- Novel approaches to diagnosis and management of hereditary transthyretin amyloidosis.Journal of neurology, neurosurgery, and psychiatry · 2022Review
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
AG10 is a novel, potent, and selective oral transthyretin (TTR) stabilizer being developed to treat TTR amyloidosis (ATTR). This randomized, double-blind, placebo-controlled study evaluated safety, tolerability, pharmacokinetics, and pharmacodynamics (ex vivo stabilization) of orally administered AG10 in healthy adult volunteers. Both mutant and wild-type ATTR are underdiagnosed diseases with limited therapeutic options. As TTR amyloidogenesis is initiated by dissociation of TTR tetramers destabilized due to inherited mutations or aging, AG10 is designed to treat the disease at its source. Four single and three multiple ascending dose levels of AG10 or matching placebo were orally administered. Safety and tolerability were assessed by vital signs, electrocardiogram, adverse events, and clinical laboratory tests. Pharmacokinetics were measured using a validated bioanalytical assay. Pharmacodynamics were assessed via three pharmacodynamic assays of TTR stabilization. AG10 was uniformly well tolerated, and no safety signals of clinical concern were observed. Pharmacokinetic observations included time to maximum concentration <1 hour, dose-dependent maximum concentration and area under the plasma concentration-time curve, low intersubject variability, and half-life ∼25 hr. Complete (>90%) stabilization of TTR was observed across the entire dosing interval at steady state on the highest dose tested. Serum TTR levels, an in vivo reflection of TTR stabilization by AG10, increased from baseline following 12 days of dosing. AG10 appears to be safe and well tolerated in healthy adult volunteers and can completely stabilize TTR across the dosing interval, establishing clinical proof of concept. Based on these data, AG10 has the potential to be a safe and effective treatment for patients with either mutant or wild-type ATTR.
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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.