A Randomized, Two-armed, Double-blind, Single-dose, Crossover, Two-sequence, Bioequivalence Clinical Trial to Compare PK Parameters and Safety of rFVIII-Fc (AryoGen Pharmed Co.) Versus Elocta® in PTPs With Severe Hemophilia A

The study is designed as a randomized, two-armed, double-blind, single-dose, crossover, two-sequence, active-controlled, multi-center, bioequivalence clinical trial with a primary endpoint of dose-normalized area under the curve (dnAUC last)

开始日期2023-07-22

申办/合作机构

Aryogen Pharmed

100 项与 Efmoroctocog alfa biosimilar(AryoGen Pharmed) 相关的临床结果

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100 项与 Efmoroctocog alfa biosimilar(AryoGen Pharmed) 相关的专利（医药）

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项与 Efmoroctocog alfa biosimilar(AryoGen Pharmed) 相关的文献（医药）

2023-05-01·CPT: pharmacometrics & systems pharmacology

Relationship between factor VIII levels and bleeding for rFVIII-SingleChain in severe hemophilia A: A repeated time-to-event analysis.

Article

作者: Bukkems, Laura H. ; Cnossen, Marjon H. ; Karlsson, Mats O. ; Mathot, Ron A. A. ; the OPTI-CLOT studies and the SYMPHONY consortium ; Jonsson, Siv

Publications on the exposure-effect relationships of factor concentrates for hemophilia treatment are limited, whereas such analyses give insight on treatment efficacy. Our objective was to examine the relationship between the dose, factor VIII (FVIII) levels and bleeding for rFVIII-SingleChain (lonoctocog alfa, Afstyla). Data from persons with severe hemophilia A on rFVIII-SingleChain prophylaxis from three clinical trials were combined. The published rFVIII-SingleChain population pharmacokinetic (PK) model was evaluated and expanded. The probability of bleeding was described with a parametric repeated time-to-event (RTTE) model. Data included 2080 bleeds, 2545 chromogenic stage assay, and 3052 one-stage assay FVIII levels from 241 persons (median age 19 years) followed for median 1090 days. The majority of the bleeds occurred in joints (65%) and the main bleeding reason was trauma (44%). The probability of bleeding decreased during follow-up and a FVIII level of 8.9 IU/dL (95% confidence interval: 6.9-10.9) decreased the bleeding hazard by 50% compared to a situation without FVIII in plasma. Variability in bleeding hazard between persons with similar FVIII levels was large, and the pre-study annual bleeding rate explained part of this variability. When a FVIII trough level of 1 or 3 IU/dL is targeted during prophylaxis, simulations predicted two (90% prediction interval [PI]: 0-17) or one (90% PI: 0-11) bleeds per year, respectively. In conclusion, the developed PK-RTTE model adequately described the relationship between dose, FVIII levels and bleeds for rFVIII-SingleChain. The obtained estimates were in agreement with those published for the FVIII concentrates BAY 81-8973 (octocog alfa) and BAY 94-9027 (damoctocog alfa pegol), indicating similar efficacy to reduce bleeding.

2023-03-13·Journal of clinical medicine

Clinical Predictors and Prediction Models for rFVIII-Fc Half Life in Real-World People with Severe Hemophilia A.

Article

作者: Liao, Yu-Mei ; Ku, Jung-Tzu ; Lin, Pei-Chin ; Chen, Yeu-Chin ; Liu, Yen-Lin ; Tsai, Chen-Hua ; Weng, Te-Fu ; Lai, Shiue-Wei ; Chang, Chia-Yau ; Tsai, Jia-Ruey ; Hu, Shu-Hsia ; Chiou, Shyh-Shin ; Cheng, Chao-Neng

The half life of recombinant factor VIII-Fc (rFVIII-Fc) for people with hemophilia A (PwHA) varies greatly. Understanding the factors influencing the variation and assessment of rFVIII-Fc half life is important for personalized treatment. Eighty-five severe-type PwHA with rFVIII-Fc treatment receiving an evaluation of half life by the Web-Accessible Population Pharmacokinetic (PK) Service-Hemophilia during 2019-2021 were retrospectively enrolled. The 50-patient PK profiles before 2021 were used for analysis and developing prediction models of half life, and the 35-patient PK profiles in 2021 were used for external validation. The patients in the development cohort were aged 8-64, with a median rFVIII-Fc half life of 20.75 h (range, 8.25-41.5 h). By multivariate linear regression analysis, we found two, four, and five predictors of rFVIII-Fc half life for the blood groups non-O, O patients, and overall patients, respectively, including baseline VWF:Ag, BMI, VWF:activity/VWF:Ag ratio, body weight, O blood group, inhibitor history, HCV infection, and hematocrit. The three prediction equations of rFVIII-Fc half life (T) were respectively developed as T for non-O group patients = -0.81 + 0.63 × (BMI, kg/m²) + 6.07 × (baseline VWF:Ag, IU/mL), T for O group patients = -0.68 + 13.30 × (baseline VWF:Ag, IU/mL) + 0.27 × (BW, kg) - 1.17 × (BMI, kg/m²) + 16.02 × (VWF:activity/VWF:Ag ratio), and T for overall patients = -1.76 + 7.24 × (baseline VWF:Ag, IU/mL) - 3.84 × (Inhibitor history) + 2.99 × (HCV infection) - 2.83 × (O blood group) + 0.30 × (Hct, %), which explained 51.97%, 75.17%, and 66.38% of the half life variability, respectively. For external validation, there was a significant correlation between the predicted and observed half lives in the validation cohort. The median half life deviation was +1.53 h, +1.28 h, and +1.79 h for the equations of non-O group, O group, and overall group patients, respectively. In total, eight predictors influencing rFVIII-Fc half life were identified. Prediction equations of rFVIII-Fc half life were developed for the non-O and O blood groups and overall PwHA with a good degree of external validation. The equations could be applied to patients aged 8-64 without the need for PK blood sampling and clinically valuable for personalized therapy.

2022-10-01·European Journal of Clinical Investigation

rFVIII‐Fc in severe haemophilia A: The incentive switch in case of high risk of joint bleedings

Article

作者: Wargny, Matthieu ; Ardillon, Laurent ; Cussac, Vincent ; Beurrier, Philippe ; Horvais, Valérie ; Trossaërt, Marc ; Pan‐Petesch, Brigitte ; Repessé, Yohann ; Guillet, Benoît

AbstractBackgroundEfmoroctocog alfa, the first recombinant factor VIII fusion protein with extended half‐life (rFVIII‐Fc), has been hypothesized to lower FVIII consumption in patients with severe Haemophilia A (pwSHA), without reducing clinical efficacy. What about real life?MethodMOTHIF‐II was a noninterventional, multicentre, before/after study, via the collection of retrospective data from July 2015 to June 2016 (called T1), and from July 2017 to June 2018 (called T2), in 7 French haemophilia treatment centres. We examined the prescriptions and dispensations of factor VIII and the Annual Bleeding Rate (ABR), in pwSHA without current inhibitors on prophylaxis, before and after the introduction of rFVIII‐Fc. The data gathered from the BERHLINGO research database and from the French Healthcare claims database with a determinist pairing process based on the national unique identification number.ResultsA total of 156 pwSHA were included in the prescription cohort and 83 in the ABR cohort. For switched patients, the mean amounts of prescribed FVIII were significantly higher during T1 compared to T2 (4333 (2052) vs. 3921 (2029) IU/kg/year/patient, p: 0.028); a significant decrease in their ABR was also observed between T1 and T2 (6.3 (6.0) vs. 4.4 (5.4), p: 0.047). These patients had a more severe bleeding profile centred on haemarthrosis.ConclusionThe results are related to those of the pivotal clinical trials for the reduction in FVIII consumption following the switch to rFVIII‐Fc, with a significant improvement in the haemorrhagic phenotype for pwSHA.

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适应症	最高研发状态	国家/地区	公司	日期
血友病A	临床3期	伊朗	Aryogen Pharmed	2023-07-22

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


ISTH2020	N/A	血友病A Von Willebrand Factor Levels \| Factor VIII (FVIII) Pharmacokinetics	20	rFVIII-Fc	(襯壓餘鏇顧網積膚積壓) = 鹹簾醖齋遞鏇積艱鏇鑰築繭襯壓繭窪膚衊膚艱 (衊鏇選積顧醖膚鹽餘鏇 ) 更多	-	2020-07-12
ISTH2019	N/A	血友病A	35	rFVIII-Fc	獵鑰糧遞壓鹽繭獵憲顧(齋蓋糧製窪鏇廠衊範構) = 遞艱觸膚鹹憲襯願餘範網鏇壓製夢衊獵艱膚夢 (糧膚願選淵衊鏇鏇齋顧 ) 更多	-	2019-06-10