Trial reportClinical and translational science2022
Phase 1 clinical trial evaluating safety, exposure and pharmacodynamics of BTK inhibitor tolebrutinib (PRN2246, SAR442168).
Trial report in Clinical and translational science, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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.
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
26 citing papers in PubMed, 47 citations in OpenAlex.
- Phase 1 clinical trial evaluating safety, exposure and pharmacodynamics of BTK inhibitor tolebrutinib (PRN2246, SAR442168).Clinical and translational science · 2022Trial
- Utilization of Brain Physiologically Based Pharmacokinetic Modeling in Support of CNS Drug Development: Case Example of Fenebrutinib.The AAPS journal · 2026Article
- Review
- Bruton's Tyrosine Kinase Inhibitors in Multiple Sclerosis: Mechanistic Considerations Across Relapsing and Progressive Disease.Molecules (Basel, Switzerland) · 2026Review
- Tolebrutinib: First Approval.Drugs · 2026Review
- High lymphocyte count and bleeding risk in patients with chronic lymphocytic leukemia treated with Bruton's tyrosine kinase inhibitors.Wiener klinische Wochenschrift · 2025Article
- Tolebrutinib Phase 2b Long-Term Extension Study: Two-Year Safety, MRI, and Clinical Efficacy Outcomes in Patients With Relapsing Multiple Sclerosis Patients.Neurology open access · 2025Article
- Beyond relapses: How BTK inhibitors are shaping the future of progressive MS treatment.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2025Review
- Update on novel multiple sclerosis treatments: from dismal defeat to scintillating success.Current opinion in neurology · 2025Review
- The mechanism of lineage-specific tRNA recognition by bacterial tryptophanyl-tRNA synthetase and its implications for inhibitor discovery.Nucleic acids research · 2025Article
- New Frontiers in Multiple Sclerosis Treatment: From Targeting Costimulatory Molecules to Bispecific Antibodies.International journal of molecular sciences · 2025Review
- Advancements in research on the cardiovascular toxicity caused by TEC family kinases inhibitors.Frontiers in pharmacology · 2025Review
- Towards Treating Multiple Sclerosis Progression.Pharmaceuticals (Basel, Switzerland) · 2024Review
- Predicted Expenditure for Prescription Drugs for Multiple Sclerosis in the Italian Market Between 2023 and 2028: Results of the Oracle Project.Neurology and therapy · 2024Article
- Bruton Tyrosine Kinase Inhibition Decreases Inflammation and Differentially Impacts Phagocytosis and Cellular Metabolism in Mouse- and Human-derived Myeloid Cells.ImmunoHorizons · 2024Article
- Comparative CNS Pharmacology of the Bruton's Tyrosine Kinase (BTK) Inhibitor Tolebrutinib Versus Other BTK Inhibitor Candidates for Treating Multiple Sclerosis.Drugs in R&D · 2024Article
- A review of Bruton's tyrosine kinase inhibitors in multiple sclerosis.Therapeutic advances in neurological disorders · 2024Review
- Absorption, Metabolism, and Excretion of [Clinical drug investigation · 2023Article
- Bruton tyrosine kinase inhibitors for multiple sclerosis.Nature reviews. Neurology · 2023Review
- Bioavailable central nervous system disease-modifying therapies for multiple sclerosis.Frontiers in immunology · 2023Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
Abstract
Bruton's tyrosine kinase (BTK), expressed in B cells and cells of innate immunity, including microglia, is an essential signaling element downstream of the B-cell receptor and Fc-receptors. Tolebrutinib (PRN2246, SAR442168) is a potent BTK inhibitor that covalently binds the kinase, resulting in durable inhibition with the potential to target inflammation in the periphery and central nervous system (CNS). Tolebrutinib crosses the blood-brain barrier and potently inhibits BTK in microglial cells isolated from the CNS. A first-in-human randomized, double-blind, placebo-controlled study of tolebrutinib was conducted. The trial design consisted of five single ascending dose arms with oral administration of a single dose of 5, 15, 30, 60, and 120 mg (n = 6 per arm, n = 2 placebo), five multiple ascending dose arms with oral administration of 7.5, 15, 30, 60, and 90 mg (n = 8 per arm, n = 2 placebo) over 10 days, and one arm (n = 4) in which cerebral spinal fluid (CSF) exposure was measured 2 h after a single 120 mg dose. Tolebrutinib was well-tolerated in the study and all treatment-related treatment emergent adverse events were mild. Tolebrutinib was rapidly absorbed following oral administration with a rapid half-life of ~ 2 h. Peripheral BTK occupancy was assessed at various timepoints by an enzyme-linked immunosorbent assay-based readout using an irreversible probe. Assessments demonstrated extensive and prolonged peripheral BTK occupancy at steady-state with once daily doses as low as 7.5 mg. Further, CSF exposure was demonstrated 2 h after administration at 120 mg.
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Identifiers
What OpenQuestion holds
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.