www.HemophiliaTreatmentReport.com
https://clinicaltrials.gov/ct2/show/NCT03196297?type=Intr&cond=hemophilia&lupd_s=05%2F08%2F2019&lupd_d=14
Conditions : Haemostasis; Haemophilia A
Interventions : Drug: Concizumab; Drug: Turoctocog alfa
Sponsor : Novo Nordisk A/S
Active, not recruiting
A Trial Evaluating Efficacy and Safety of Prophylactic Administration of Concizumab in Patients With Severe Haemophilia A Without Inhibitors
NCT03196297
Thu, 22 Jun 2017 12:00:00 EDT
Last Update Posted: 05/22/19 07:39AM
https://clinicaltrials.gov/ct2/show/NCT03196284?type=Intr&cond=hemophilia&lupd_s=05%2F08%2F2019&lupd_d=14
Conditions : Congenital Bleeding Disorder; Haemophilia A With Inhibitors; Haemophilia B With Inhibitors
Interventions : Drug: Concizumab; Drug: Eptacog alfa
Sponsor : Novo Nordisk A/S
Active, not recruiting
A Trial Evaluating the Efficacy and Safety of Prophylactic Administration of Concizumab in Haemophilia A and B Patients With Inhibitors
NCT03196284
Thu, 22 Jun 2017 12:00:00 EDT
Last Update Posted: 05/22/19 07:39AM
https://www.ncbi.nlm.nih.gov/pubmed/30408848?dopt=Abstract
Related Articles
Concizumab restores thrombin generation potential in patients with haemophilia: Pharmacokinetic/pharmacodynamic modelling results of concizumab phase 1/1b data.
Haemophilia. 2019 Jan;25(1):60-66
Authors: Eichler H, Angchaisuksiri P, Kavakli K, Knoebl P, Windyga J, Jiménez-Yuste V, Harder Delff P, Chowdary P
Abstract
INTRODUCTION: Concizumab enhances thrombin generation (TG) potential in haemophilia patients by inhibiting tissue factor pathway inhibitor (TFPI). In EXPLORER3 (phase 1b), a dose-dependent pharmacokinetic/pharmacodynamic (PK/PD) relationship was confirmed between concizumab dose, free TFPI and TG potential.
AIM: Determine the association between concizumab exposure, PD markers (free TFPI; peak TG) and bleeding episodes to establish the minimum concizumab concentration for achieving sufficient efficacy.
METHODS: Free TFPI predictions were generated using an estimated concizumab-free TFPI exposure-response (Emax ) model based on concizumab phase 1/1b data for which simultaneously collected concizumab and free TFPI samples were available. Concizumab concentration at the time of a bleed was predicted using a PK model, based on available data for concizumab doses >50 μg/kg to ≤9 mg/kg. Peak TG vs concizumab concentration analyses and an Emax model were constructed based on EXPLORER3 observations.
RESULTS: The Emax model showed a tight PK/PD relationship between concizumab exposure and free TFPI; free TFPI decreased with increasing concizumab concentration. A strong correlation between concizumab concentration and peak TG was observed; concizumab >100 ng/mL re-established TG potential to within the normal reference range. Estimated EC50 values for the identified concizumab-free TFPI and concizumab-TG potential models were very similar, supporting free TFPI as an important biomarker. A correlation between bleeding episode frequency and concizumab concentration was indicated; patients with a concizumab concentration >100 ng/mL experienced less frequent bleeding. The PK model predicted that once-daily dosing would minimize within-patient concizumab PK variability.
CONCLUSION: Concizumab phase 2 trials will target an exposure ≥100 ng/mL, with a once-daily regimen.
PMID: 30408848 [PubMed – indexed for MEDLINE]
