Study to Compare How the Body Distributes and Excretes the Drugs Jivi (BAY 94-9027) and Adynovi in Patients With Severe Hemophilia A (Bleeding Disorder Resulting From a Lack of Blood Clotting Factor VIII)

Study Overview
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Brief Summary
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This study is being conducted to compare how the body distributes and excretes the drugs Jivi (BAY 94-9027) and Adynovi. Jivi is a recently approved blood clotting Factor VIII (FVIII) medication for the treatment of hemophilia A (bleeding disorder resulting from a lack of FVIII). Both drugs are FVIII products which have been manufactured via recombinant technology and have an extended half-live, i.e. they will stay longer in the body than other FVIII products. Therefore these products act longer in the body which reduces the frequency of drug injections. To compare the two drugs, a cross-over design was chosen, i.e. each patient will receive both products one after another. Patients participating in this study will receive one dose of Jivi and one dose of Adynovi. Both drugs are injected into a vein. Observation will last for about 10 weeks, and blood samples will be taken from the participants to measure the blood levels of FVIII. Generic name of Jivi is Damoctocog-alfa-pegol, generic name of Adynovi is Rurioctocog alfa pegol.

Official Title
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Single Dose, Open Label, Randomized, Cross-over Study in Participants With Severe Hemophilia A Comparing Pharmacokinetic Parameters of BAY 94-9027 and Adynovi

Conditions
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Hemophilia A

Intervention / Treatment
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* Biological: Damoctocog-alfa-pegol (BAY94-9027, Jivi)
* Biological: Rurioctocog alfa pegol (Adynovi)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participants with severe hemophilia A (baseline FVIII activity FVIII:C <1%), determined by measurement at the time of screening (following a washout period of at least 72 h after their last FVIII treatment for standard half-life FVIII products or of 120 h for extended half-life FVIII products) or from reliable prior documentation (e.g. measurement in other clinical studies, result from approved clinical laboratory or diagnostic genetic testing). ≥150 exposure days with FVIII concentrate(s) (plasma-derived or recombinant) as supported by medical records. Body mass index (BMI) within the range 18 kg/m2 to 29.9 kg/m2 (inclusive). Exclusion Criteria: Inability to stop FVIII treatment to complete a minimum of 72 h washout for standard half-life FVIII product or 120 h washout for extended half-life FVIII product Evidence of current or past inhibitor antibody History of any congenital or acquired coagulation disorders other than hemophilia A Platelet count <75,000/mm3 Human immunodeficiency virus (HIV) infection with a cluster of differentiation 4 (CD4+) lymphocyte count of <200/mm3 Abnormal renal function (serum creatinine >2x the upper limit of the normal range [ULN]) Active liver disease verified by medical history or persistently elevated alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >5x ULN or severe liver disease as evidenced by, but not limited to any of the following: International Normalized Ratio >1.4, hypoalbuminemia, portal vein hypertension including presence of otherwise unexplained splenomegaly and history of esophageal varices Requirement of any pre-medication to tolerate FVIII treatment (e.g. anti-histamines) Prior treatment with immunomodulatory agents or chemotherapy within the last 3 months prior to study entry or requirement of treatment during the study. The following drugs are allowed: α interferon, PEG interferon, highly active anti-retroviral therapy for HIV, and/or a total of two courses of pulse treatment with steroid for a maximum of 7 days at 1 mg/kg or less

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BAY94-9027 / Adynovi<br>Treatment sequence A-B with washout before each treatment | Biological: Damoctocog-alfa-pegol (BAY94-9027, Jivi)<br>* Single dose, 50 IU/kg BAY94-9027 (IU: international Units)<br>Biological: Rurioctocog alfa pegol (Adynovi)<br>* Single dose, 50 IU/kg Adynovi<br>|
| Experimental: Adynovi / BAY94-9027<br>Treatment sequence B-A with washout before each treatment | Biological: Damoctocog-alfa-pegol (BAY94-9027, Jivi)<br>* Single dose, 50 IU/kg BAY94-9027 (IU: international Units)<br>Biological: Rurioctocog alfa pegol (Adynovi)<br>* Single dose, 50 IU/kg Adynovi<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area under the concentration versus time curve from time 0 to the last data point (AUC(0-tlast)) for BAY 94-9027 |  | Pre-dose to 120 hours after the end of the infusion | 
| Area under the concentration versus time curve from time 0 to the last data point (AUC(0-tlast)) for Adynovi |  | Pre-dose to 120 hours after the end of the infusion |