Clinical trial NCT01029340: Trial to Evaluate the Efficacy and Safety of a New Full Length Recombinant Human FVIII for Hemophilia A
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Blood Coagulation Disorders
Hemophilia A
Keywords: Hemophilia A
Factor VIII
Prophylaxis
Lead sponsor: Bayer
Sponsor class: INDUSTRY
First posted: 2009-12-09
Enrollment: 74
Sex: MALE
Minimum age (years): 12
Maximum age (years): 65
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief 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)


Eligibility criteria: 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

Primary outcomes:
measure: Part A - Area Under the Drug Concentration-time Curve (AUC)
timeFrame: 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.
measure: Part A - Half-life (t 1/2)
timeFrame: Samples taken at pre-injection, and at 0.25, 0.5, 1, 3, 6, 8, 24, 30 and 48 hours post injection.
measure: Part B - Annualized Number of Total Bleeds
timeFrame: 12 months after randomization
Secondary outcomes:
measure: Part B - The in Vivo Recovery Values of Human Factor VIII (FVIII)
timeFrame: 15-30 minutes after the injection
measure: Part B - Annualized Number of Bleeds in Each 6-month Potency Assignment Period
timeFrame: 6 months on each potency
measure: Part B - Control of Bleeding as Measured by the Number of Injections Required to Treat a Bleed
timeFrame: 6 months on each potency
measure: Part B - Changes From Baseline at 12 Months in Quality of Life (QoL) as Measured by Transformed Total Score of Haemo-QoL Questionnaire
timeFrame: Baseline and 12 months
measure: Part B - Changes From Baseline at 12 Months in Utility Index as Measured by EQ-5D Questionaire
timeFrame: Baseline and 12 months
measure: Part A - Number of Participants With Inhibitory Antibody Formation
timeFrame: Up to 6 weeks after first injection of study drug
measure: Part B - Number of Participants With Incidence of Inhibitory Antibody Formation
timeFrame: Up to 12 months after drug administration
measure: Part C - Number of Participants With Incidence of Inhibitory Antibody Formation
timeFrame: before and 3 weeks after surgery
measure: Part A - Number of Participants With Incidence of Antibody Formation to Heat-shock Protein (HSP-70)
timeFrame: Up to 6 weeks after drug administration
measure: Part B - Number of Participants With Incidence of Antibody Formation to Heat-shock Protein (HSP-70)
timeFrame: Up to 12 months after drug administration
measure: Part C - Number of Participants With Incidence of Antibody Formation to Heat-shock Protein (HSP-70)
timeFrame: before and 3 weeks after surgery
measure: Part A - Number of Participants With Incidence of Antibody Formation to Host Cell Proteins (HCP)
timeFrame: Up to 4 weeks after drug administration
measure: Part B - Number of Participants With Incidence of Antibody Formation to Host Cell Proteins (HCP)
timeFrame: Up to 12 months after drug administration
measure: Part C - Number of Participants With Incidence of Antibody Formation to Host Cell Proteins (HCP)
timeFrame: before and 3 weeks after surgery
measure: Part B - Number of Participants With Assessment of the Hemostasis During Major Surgery
timeFrame: An average of 1 month after start of treatment
measure: Part C - Number of Participants With Assessment of the Hemostasis During Major Surgery
timeFrame: at the time of surgery
Other outcomes:
Locations:
city: Orange
country: United States
state: California
city: Sacramento
country: United States
state: California
city: Tampa
country: United States
state: Florida
city: Boston
country: United States
state: Massachusetts
city: East Lansing
country: United States
state: Michigan
city: Kansas City
country: United States
state: Missouri
city: Cleveland
country: United States
state: Ohio
city: Bahia Blanca
country: Argentina
state: Buenos Aires
city: Rosario
country: Argentina
state: Santa Fe
city: Graz
country: Austria
city: Wien
country: Austria
city: Zagreb
country: Croatia
city: DK-Aarhus N
country: Denmark
city: Frankfurt
country: Germany
state: Hessen
city: Bonn
country: Germany
state: Nordrhein-Westfalen
city: Mainz
country: Germany
state: Rheinland-Pfalz
city: Homburg
country: Germany
state: Saarland
city: Magdeburg
country: Germany
state: Sachsen-Anhalt
city: Hongkong
country: Hong Kong
city: Bangalore
country: India
city: Mumbai
country: India
city: Pune
country: India
city: Jakarta
country: Indonesia
city: Ramat Gan
country: Israel
city: Catanzaro
country: Italy
state: Calabria
city: Napoli
country: Italy
state: Campania
city: Napoli
country: Italy
state: Campania
city: Roma
country: Italy
state: Lazio
city: Milano
country: Italy
state: Lombardia
city: Vicenza
country: Italy
state: Veneto
city: Oslo
country: Norway
city: Karachi
country: Pakistan
city: Krakow
country: Poland
city: Warszawa
country: Poland
city: Belgrade
country: Serbia
city: Beograd
country: Serbia
city: Nis
country: Serbia
city: Novi Sad
country: Serbia
city: Pretoria
country: South Africa
state: Gauteng
city: Parktown
country: South Africa
city: Oviedo
country: Spain
state: Asturias
city: Santander
country: Spain
state: Cantabria
city: A Coruña
country: Spain
city: Barcelona
country: Spain
city: Jaén
country: Spain
city: Valencia
country: Spain
city: Göteborg
country: Sweden
city: Malmö
country: Sweden
city: Stockholm
country: Sweden
facility: Karolinska Universitetssjukhuset i Solna
city: Changhua
country: Taiwan
city: Taipei
country: Taiwan
city: Taipei
country: Taiwan
city: Bangkok
country: Thailand
city: Bangkok
country: Thailand
city: Adana
country: Turkey
city: Antalya
country: Turkey
city: Izmir
country: Turkey
city: Dundee
country: United Kingdom
state: Dundee City
city: Oxford
country: United Kingdom
state: Oxfordshire
city: Sheffield
country: United Kingdom
state: South Yorkshire
city: London
country: United Kingdom
Study officials:
affiliation: Bayer
name: Bayer Study Director
role: STUDY_DIRECTOR
References:
citation: Kitchen S, Katterle Y, Beckmann H, Maas Enriquez M. Chromogenic assay for BAY 81-8973 potency assignment has no impact on clinical outcome or monitoring in patient samples. J Thromb Haemost. 2016 Jun;14(6):1192-9. doi: 10.1111/jth.13322. Epub 2016 May 3.
citation: Oldenburg J, Windyga J, Hampton K, Lalezari S, Tseneklidou-Stoeter D, Beckmann H, Maas Enriquez M. Safety and efficacy of BAY 81-8973 for surgery in previously treated patients with haemophilia A: results of the LEOPOLD clinical trial programme. Haemophilia. 2016 May;22(3):349-53. doi: 10.1111/hae.12839. Epub 2016 Mar 1.
citation: Saxena K, Lalezari S, Oldenburg J, Tseneklidou-Stoeter D, Beckmann H, Yoon M, Maas Enriquez M. Efficacy and safety of BAY 81-8973, a full-length recombinant factor VIII: results from the LEOPOLD I trial. Haemophilia. 2016 Sep;22(5):706-12. doi: 10.1111/hae.12952. Epub 2016 Jun 24.