Article detail · 2019
Subcutaneous concizumab prophylaxis in hemophilia A and hemophilia A/B with inhibitors: phase 2 trial results
- Year
- 2019
- Type
- article
Data source split
- YÖKSİS YÖKSİS article record
- YÖKSİS venue Blood
- Catalog match (ISSN) Blood
- OpenAlex OpenAlex enrichment (abstract, citations, topics)
Abstract
OpenAlex · English
Results from the main parts (24 weeks) of 2 concizumab phase 2 trials are presented: explorer4 in hemophilia A (HA) or B (HB) with inhibitors (HAwI/HBwI) and explorer5 in HA. The trials aimed to evaluate the efficacy of daily subcutaneous concizumab prophylaxis (evaluated as annualized bleeding rate [ABR] at last dose level), with secondary objectives being safety and immunogenicity (assessed as number of adverse events [AEs] and antidrug antibodies [ADAs]). Patients received 0.15 mg/kg concizumab, with potential dose escalation to 0.20 and 0.25 mg/kg (if ≥3 spontaneous bleeding episodes within 12 weeks of concizumab treatment). Relevant pharmacokinetic/pharmacodynamic (PK/PD) parameters were assessed. Thirty-six HA, 9 HAwI, and 8 HBwI patients were exposed to concizumab. Most inhibitor patients (15 of 17; 88.2%) did not escalate the dose; all patients chose to continue to the extension phase of the trials. Clinical proof of concept for prevention of bleeding episodes was demonstrated in both trials. Estimated ABRs in HAwI and HBwI were lower vs HA: 3.0 (95% confidence interval [CI], 1.7; 5.3) and 5.9 (95% CI, 4.2; 8.5) vs 7.0 (95% CI, 4.6; 10.7), respectively. PK/PD results were as expected, with no difference between hemophilia subtypes for concizumab exposure, free tissue factor pathway inhibitor, thrombin generation, prothrombin fragment 1+2, and d-dimers. Concizumab was safe and well tolerated (no severe AEs, AE-related withdrawals, or thromboembolic events). Three patients had (very low to medium titer) ADA+ tests in each trial, with no observed clinical effect. These results support further development of concizumab as a daily prophylactic treatment in all hemophilia patients. These trials were registered at www.clinicaltrials.gov as #NCT03196284 and #NCT03196297.
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Citations
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154 citations
OpenAlex cited_by_count (cache / database)
5 publications in the local catalog that cite this work (OpenAlex reference match; not the full global list).
- Phase 3 Trial of Concizumab in Hemophilia with Inhibitors 2023
- Long-term efficacy and safety of subcutaneous concizumab prophylaxis in hemophilia A and hemophilia A/B with inhibitors 2022
- Gene therapy in haemophilia: literature review and regional perspectives for Turkey 2022
- Gene therapy in haemophilia: literature review and regional perspectives for Turkey 2022
- New Treatment Modalities in Hemophilia 2022