Trial to Evaluate the Efficacy and Safety of a New Full Length Recombinant Human FVIII for Hemophilia A

Hemophilia A Clinical Trial

— Leopold I  

Official title:

A Two Part Randomized Cross-Over Trial to Evaluate the Pharmacokinetics, Efficacy, and Safety Profile of Plasma Protein-Free Recombinant FVIII Formulated With Sucrose (BAY81-8973) in Previously Treated Subjects With Severe Hemophilia A Under Prophylaxis Therapy

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01029340
• Other study ID #: 12954
• Secondary ID: 2009-012149-43
• Status: Completed
• Phase: Phase 3
• First received: December 8, 2009
• Last updated: July 14, 2015
• Start date: December 2009
• Est. completion date: March 2013

Study information

• Verified date: July 2015
• Source: Bayer
• Contact: n/a
• Is FDA regulated: No
• Health authority: Austria: Agency for Health and Food SafetyChina: Food and Drug AdministrationFinland: Finnish Medicines AgencyGermany: Paul-Ehrlich-InstitutHong Kong: Department of HealthIndonesia: National Agency of Drug and Food ControlIsrael: Ministry of HealthItaly: The Italian Medicines AgencyNorway: Norwegian Medicines AgencySpain: Spanish Agency of MedicinesSweden: Medical Products AgencyUnited Kingdom: Medicines and Healthcare Products Regulatory AgencyTaiwan: Department of HealthDenmark: Danish Medicines AgencyPoland: Office for Registration of Medicinal Products, Medical Devices and Biocidal ProductsUnited States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

The study will assess the pharmacokinetics (part A) safety, tolerability, and efficacy of prophylaxis treatment (2 to 3 times a week) (part B) with BAY81-8973 over a one year period (split into two six month treatment periods). The study will compare 2 different methods (assays) for measuring the amount of study drug, the chromogenic substrate assay per European Pharmacopeia (CS/EP) with the classical assay (Chromogenic Substrate Adjusted, CS/ADJ). During one six month period patients will receive the study drug where the dose has been measured using the" (CS/EP) and during the other six months period the dose will be measured based on the Chromogenic Substrate Adjusted assay CS/ADJ)

Recruitment information / eligibility

• Status: Completed
• Enrollment: 74
• Est. completion date: March 2013
• Est. primary completion date: June 2012
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 12 Years to 65 Years

Eligibility

Inclusion Criteria:

• Male, aged 12 to 65 years

• Severe hemophilia A defined as < 1% FVIII:C

• >/= 150 days of previous treatment with FVIII in lifetime

• Currently receiving on-demand or any type of prophylaxis treatment regimen with any FVIII product

• No history of or current FVIII inhibitors

Exclusion Criteria:

• Presence of another bleeding disease that is different from hemophilia A (e.g., von Willebrand disease, hemophilia B)

• Low platelet count, abnormal kidney function, or liver disease

• Received treatment with immune suppressing drugs within the last 3 months prior or requires treatment during the study. (Some drugs for hepatitis C, Human immunodeficiency virus (HIV), and steroids are allowed)

• Receiving or has received other experimental drugs within 3 months prior to study entry

• Allergy to Factor VIII or hamsters or mouse protein

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Crossover Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Blood Coagulation Disorders
• Hemophilia A
• Hemostatic Disorders

Intervention

Biological:
• Recombinant Factor VIII (BAY81-8973)
Single dose of BAY81-8973 crossed over to single dose of Kogenate FS
• Recombinant Factor VIII (Kogenate FS, BAY14-2222)
Single dose of Kogenate FS crossed over to Single dose of BAY81-8973
• Recombinant Factor VIII (BAY81-8973)
Participants received IV injections of BAY81-8973 at 20-50 IU/kg 2-3 times per week with BAY81-8973 measured by Chromogenic Substrate Assay Potency Per European Pharmacopeia (CS/EP) for 6 months and by Chromogenic Substrate Assay/Adjusted to Label Potency (CS/ADJ) for 6 months, sequence according to randomization.
• Recombinant Factor VIII (BAY81-8973)
Participants received a loading dose of approximately 50 IU/kg of BAY 81-8973 before the first surgical incision followed by further treatment with BAY 81-8973 according to surgical requirements for up to 3 weeks

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Bayer

Countries where clinical trial is conducted

United States,  Argentina,  Austria,  Croatia,  Denmark,  Germany,  Hong Kong,  India,  Indonesia,  Israel,  Italy,  Norway,  Pakistan,  Poland,  Serbia,  South Africa,  Spain,  Sweden,  Taiwan,  Thailand,  Turkey,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Part A - Area Under the Drug Concentration-time Curve (AUC)	To examine the Pharmacokinetic (PK) characteristics of BAY 81-8973 and ensure that the new drug is similar to Kogenate FS. All results are based on the chromogenic assay.	Samples taken at pre-injection, and at 0.25, 0.5, 1, 3, 6, 8, 24, 30 and 48 hours post injection. AUC calculated from time of injection to infinity.	No
Primary	Part A - Half-life (t 1/2)	To examine the PK characteristics of BAY81-8973 and ensure that the new drug is similar to Kogenate FS. All results are based on the chromogenic assay.	Samples taken at pre-injection, and at 0.25, 0.5, 1, 3, 6, 8, 24, 30 and 48 hours post injection.	No
Primary	Part B - Annualized Number of Total Bleeds	The annualized number of bleeds experienced by participants	12 months after randomization	No
Secondary	Part B - The in Vivo Recovery Values of Human Factor VIII (FVIII)	The amount of Factor VIII found in blood samples taken after the injection of the study drug at the beginning of the CS/EP treatment period.	15-30 minutes after the injection	No
Secondary	Part B - Annualized Number of Bleeds in Each 6-month Potency Assignment Period	The annualized number of bleeds experienced by participants in each of the two treatment periods	6 months on each potency	No
Secondary	Part B - Control of Bleeding as Measured by the Number of Injections Required to Treat a Bleed	The number of injections needed by participants to stop a bleed	6 months on each potency	No
Secondary	Part B - Changes From Baseline at 12 Months in Quality of Life (QoL) as Measured by Transformed Total Score of Haemo-QoL Questionnaire	A measure of how treatment with BAY81-8973 affected the daily life of participants. the scoring system has 100 points. 0 is the worst possible score. 100 is the best possible score. Positive changes from baseline indicate an improvement in quality of life and negative changes indicate a deterioration.	Baseline and 12 months	No
Secondary	Part B - Changes From Baseline at 12 Months in Utility Index as Measured by EQ-5D Questionaire	A measure of how treatment with BAY81-8973 affected the daily life of participants. 1.0 = Best possible score, -0.594 = Worst possible score. Positive changes from baseline indicate an improvement and negative changes indicate a deterioration.	Baseline and 12 months	No
Secondary	Part A - Number of Participants With Inhibitory Antibody Formation	A test to ensure that participants have not developed antibodies that will interfere with the action of BAY81-8973	Up to 6 weeks after first injection of study drug	Yes
Secondary	Part B - Number of Participants With Incidence of Inhibitory Antibody Formation	A test to ensure that participants have not developed antibodies that will interfere with the action of BAY81-8973	Up to 12 months after drug administration	Yes
Secondary	Part C - Number of Participants With Incidence of Inhibitory Antibody Formation	A test to ensure that participants have not developed antibodies that will interfere with the action of BAY81-8973	before and 3 weeks after surgery	Yes
Secondary	Part A - Number of Participants With Incidence of Antibody Formation to Heat-shock Protein (HSP-70)	A test to analyze the formation of antibodies to HSP-70	Up to 6 weeks after drug administration	Yes
Secondary	Part B - Number of Participants With Incidence of Antibody Formation to Heat-shock Protein (HSP-70)	A test to analyze the formation of antibodies to HSP-70	Up to 12 months after drug administration	Yes
Secondary	Part C - Number of Participants With Incidence of Antibody Formation to Heat-shock Protein (HSP-70)	A test to analyze the formation of antibodies to HSP-70	before and 3 weeks after surgery	Yes
Secondary	Part A - Number of Participants With Incidence of Antibody Formation to Host Cell Proteins (HCP)	A test to ensure that participants have not developed antibodies to HCP during the study	Up to 4 weeks after drug administration	Yes
Secondary	Part B - Number of Participants With Incidence of Antibody Formation to Host Cell Proteins (HCP)	A test to ensure that participants have not developed antibodies to HCP during the study	Up to 12 months after drug administration	Yes
Secondary	Part C - Number of Participants With Incidence of Antibody Formation to Host Cell Proteins (HCP)	A test to ensure that participants have not developed antibodies to HCP during the study	before and 3 weeks after surgery	Yes
Secondary	Part B - Number of Participants With Assessment of the Hemostasis During Major Surgery	An assessment made by surgeons of how effective BAY81-8973 was in stopping bleeding during major operations	An average of 1 month after start of treatment	Yes
Secondary	Part C - Number of Participants With Assessment of the Hemostasis During Major Surgery	An assessment made by surgeons of how effective BAY81-8973 was in stopping bleeding during major operations	at the time of surgery	Yes

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