Trial reportClinical pharmacokinetics2018
A Pharmacometric Approach to Substitute for a Conventional Dose-Finding Study in Rare Diseases: Example of Phase III Dose Selection for Emicizumab in Hemophilia A.
Trial report in Clinical pharmacokinetics, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT06320626 (Pharmacokinetic-guided Dosing of Emicizumab in Congenital Haemophilia A Patients - The DosEmi Study), which is not on this map. Cited by 33 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.
Pharmacokinetic-guided Dosing of Emicizumab in Congenital Haemophilia A Patients - The DosEmi Study
Who cites it
33 citing papers in PubMed, 1 synthesis or guideline pooled it, 77 citations in OpenAlex.
- Pharmacokinetics and Associated Efficacy of Emicizumab in Humans: A Systematic Review.Clinical pharmacokinetics · 2021Pooled it
- Emicizumab dose up-titration in case of suboptimal bleeding control in people with haemophilia A.Haemophilia : the official journal of the World Federation of Hemophilia · 2023Trial
- Population repeated time-to-event analysis of exacerbations in asthma patients: A novel approach for predicting asthma exacerbations based on biomarkers, spirometry, and diaries/questionnaires.CPT: pharmacometrics & systems pharmacology · 2021Trial
- Pharmacokinetics and Pharmacodynamics of Emicizumab in Persons with Hemophilia A with Factor VIII Inhibitors: HAVEN 1 Study.Thrombosis and haemostasis · 2021Trial
- Evaluation of the Pharmacokinetics, Pharmacodynamics, and Safety of a Single Dose of Emicizumab in Healthy Chinese Subjects.Clinical pharmacology in drug development · 2021Trial
- Trial
- Relative and Absolute Bioavailability Study of Emicizumab to Bridge Drug Products and Subcutaneous Injection Sites in Healthy Volunteers.Clinical pharmacology in drug development · 2019Trial
- From Small Data to Big Decisions: How Clinical Pharmacology Shapes Rare Disease Development.Journal of clinical pharmacology · 2026Review
- Emicizumab prophylaxis beyond clinical trials: a multicenter, prospective real-world study of pediatric hemophilia patients with and without inhibitors.European journal of pediatrics · 2026Article
- Emicizumab: the hemophilia A game-changer.Haematologica · 2024Review
- Exposure-Response Relationship between VWF/FVIII Activity and Spontaneous Bleeding Events Following Recombinant VWF Prophylaxis in Severe VWD.TH open : companion journal to thrombosis and haemostasis · 2024Article
- Pharmacokinetics and coagulation biomarkers in children and adults with hemophilia A receiving emicizumab prophylaxis every 1, 2, or 4 weeks.Research and practice in thrombosis and haemostasis · 2024Article
- Article
- Data mining and analysis for emicizumab adverse event signals based on the Food and Drug Administration Adverse Event Reporting System database.International journal of clinical pharmacy · 2023Article
- Efficacy of emicizumab is maintained throughout dosing intervals for bleed prophylaxis.Research and practice in thrombosis and haemostasis · 2023Article
- Optimizing maintenance dosing of emicizumab-kxwh as prophylaxis in hemophilia A: Dosing to product labeling while minimizing drug waste.Journal of managed care & specialty pharmacy · 2023Article
- Dose-finding studies in drug development for rare genetic diseases.Orphanet journal of rare diseases · 2022Article
- A Model-Based Framework to Inform the Dose Selection and Study Design of Emicizumab for Pediatric Patients With Hemophilia A.Journal of clinical pharmacology · 2022Article
- Low immunogenicity of emicizumab in persons with haemophilia A.Haemophilia : the official journal of the World Federation of Hemophilia · 2021Article
- Exposure-Bleeding Count Modeling of Emicizumab for the Prophylaxis of Bleeding in Persons with Hemophilia A with/Without Inhibitors Against Factor VIII.Clinical pharmacokinetics · 2021Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundEmicizumab (ACE910) is a bispecific antibody mimicking the cofactor function of activated coagulation factor VIII. In phase I-I/II studies, emicizumab reduced the bleeding frequency in patients with severe hemophilia A, regardless of the presence of factor VIII inhibitors, at once-weekly subcutaneous doses of 0.3, 1, and 3 mg/kg.
methodsUsing the phase I-I/II study data, population pharmacokinetic and repeated time-to-event (RTTE) modeling were performed to quantitatively characterize the relationship between the pharmacokinetics of emicizumab and reduction in bleeding frequency. Simulations were then performed to identify the minimal exposure expected to achieve zero bleeding events for 1 year in at least 50% of patients and to select the dosing regimens to be tested in phase III studies.
resultsThe RTTE model adequately predicted the bleeding onset over time as a function of plasma emicizumab concentration. Simulations suggested that plasma emicizumab concentrations of ≥ 45 μg/mL should result in zero bleeding events for 1 year in at least 50% of patients. This efficacious exposure provided the basis for selecting previously untested dosing regimens of 1.5 mg/kg once weekly, 3 mg/kg every 2 weeks, and 6 mg/kg every 4 weeks for phase III studies.
conclusionsA pharmacometric approach guided the phase III dose selection of emicizumab in hemophilia A, without conducting a conventional dose-finding study. Phase III studies with the selected dosing regimens are currently ongoing. This case study indicates that a pharmacometric approach can substitute for a conventional dose-finding study in rare diseases and will streamline the drug development process.
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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.