Clinical trial NCT00623480: Trial to Evaluate the Effect of Secondary Prophylaxis With rFVIII Therapy in Severe Hemophilia A Adult and/or Adolescent Subjects Compared to That of Episodic Treatment
Official title: Randomized, Controlled, Parallel, Prospective Trial to Evaluate the Effect of Secondary Prophylaxis With rFVIII Therapy in Severe Hemophilia A Adult and/or Adolescent Subjects, as Applicable, Compared to That of Episodic Treatment
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Hemophilia A
Keywords: Hemophilia A
Lead sponsor: Bayer
Sponsor class: INDUSTRY
First posted: 2008-02-26
Enrollment: 84
Sex: MALE
Minimum age (years): 12
Maximum age (years): 50
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: To evaluate the effect of secondary prophylaxis as compared to episodic treatment on bleeding frequency (number of bleeds per year) and on joint damage.


Eligibility criteria: Inclusion Criteria:

* Males aged 12 to 50 years (US and Argentina)
* Males aged 18 to 50 years (other countries)
* Subjects with severe hemophilia A (\<1% FVIII:C) as confirmed by the central lab from a sample obtained at least 96 hours after FVIII administration wash-out. Allow for the inclusion of a maximum of 10% (n=8) of patients with 1-2% FVIII:C baseline levels as long as they exhibit clinical severity and comply with all other inclusion criteria.
* Subjects with at least 150 prior exposure days with any FVIII
* Subjects who have been on episodic treatment and no known regular prophylaxis treatment for more than 12 consecutive months in the previous 5 years
* Subjects with 6 to 24 bleeding events and/or treatments in the previous 6 months prior to study entry which are documented and available in the subjects medical records. Documentation can include records from previous physicians, specific home treatment records, emergency room or hospital records, x-ray reports, etc. The investigator can also document with a detailed note the number of bleeds reported by the subject in the last 6 months.
* Subjects with inhibitor formation surveillance (inhibitor or recovery testing) over the ten years prior to enrollment documented by the investigator and who do not have a history of any of the following:

  * A positive inhibitor titer of 5.0 Bethesda Unit (BU) or greater by either BU assay system at any time since first exposure to exogenous factor VIII
  * A positive inhibitor test result of 1.0 or greater performed by the original BU assay at any time in the past 10 years (A subject can have more than one positive inhibitor test of 0.6 or greater by the original BU assay test but all must be less than 1.0 BU using the original BU assay.)
  * A positive inhibitor test result of 0.6 or greater performed by the Nijmegen method at any time in the past 10 years
* Subjects with no inhibitor activity by Nijmegen-modified Bethesda assay, either positive (\> 0.6 BU is considered positive) or borderline (\> 0.3 and \< 0.6 BU is considered borderline) as measured in the current study reference laboratory

Exclusion Criteria:

* Subjects with any other bleeding disease besides hemophilia A (i.e. von Willebrand disease)
* Subjects with thrombocytopenia (platelets \< 100,000/mm3)
* Subjects with abnormal renal function (Cockcroft-Gault Creatinine Clearance value of 60 mL/min or lower)
* Subjects with active hepatic disease (Aspartate aminotransferase \[AST\] or Alanine aminotransferase \[ALT\] \> 5xUpper Limit of Normal (ULN))
* Subjects on treatment with immunomodulatory agents within the last 3 months prior to study entry or during the study (the following drugs are however allowed: interferon-a treatment for Hepatitis C virus (HCV), Highly active anti-retroviral therapy (HAART) therapy for human immunodeficiency virus (HIV) and/or a total of two courses of pulse treatment with steroids for a maximum of 7 days at 1mg/kg or less)
* Subjects with an absolute CD4 lymphocyte cell count \< 200 cells/mm3 (due to HIV, HCV or another suspected medical condition)
* Subjects with known hypersensitivity to rFVIII, mouse or hamster proteins
* Subjects who are receiving or had received other experimental drugs within 1 month prior to study entry
* Subjects who require any pre-medication to tolerate FVIII injections (e.g. anti-histamines)
* Subjects who are unwilling to comply with study visits or either of the possible treatment regimens
* Subjects who have a planned orthopedic intervention to be performed during the study that may substantially affect bleeding (e.g. surgical or chemical or radiological synovectomy)
* Subjects who are not suitable for participation in this study for any reason, according to the Investigator
* Subjects who have poor joint status as defined by routine need for a wheelchair or unable to ambulate without the assistance of a brace, cane or crutches
* Three or more joints that are already fused or "frozen" also called ankylosis

Primary outcomes:
measure: Bleeding Frequency (Number of Total Bleeds)
timeFrame: After the last enrolled patient has been in the study for 1 year. At the cut-off, the median follow-up duration was 616 days (minimum was 111 days and maximum was 1109 days)
Secondary outcomes:
measure: Change From Baseline to 3 Years in the MRI (Magnetic Resonance Imaging) Scale.
timeFrame: Baseline and 3 years
measure: Change From Baseline to 3 Years in the Colorado Adult Joint Assessment Scale
timeFrame: Baseline and 3 years
Other outcomes:
measure: Change From Baseline to 3 Years in the Physical Functioning Domain of the Haemo-QoL-A
timeFrame: Baseline and 3 years
Locations:
city: Tucson
country: United States
state: Arizona
city: Little Rock
country: United States
state: Arkansas
city: Orange
country: United States
state: California
city: Sacramento
country: United States
state: California
city: Aurora
country: United States
state: Colorado
city: Washington
country: United States
state: District of Columbia
city: Orlando
country: United States
state: Florida
city: Atlanta
country: United States
state: Georgia
city: Chicago
country: United States
state: Illinois
city: Chicago
country: United States
state: Illinois
city: Indianapolis
country: United States
state: Indiana
city: Iowa City
country: United States
state: Iowa
city: Louisville
country: United States
state: Kentucky
city: Boston
country: United States
state: Massachusetts
city: Detroit
country: United States
state: Michigan
city: Minneapolis
country: United States
state: Minnesota
city: Kansas City
country: United States
state: Missouri
city: Las Vegas
country: United States
state: Nevada
city: Newark
country: United States
state: New Jersey
city: New York
country: United States
state: New York
city: New York
country: United States
state: New York
city: Cleveland
country: United States
state: Ohio
city: Hershey
country: United States
state: Pennsylvania
city: Pittsburgh
country: United States
state: Pennsylvania
city: Knoxville
country: United States
state: Tennessee
city: Houston
country: United States
state: Texas
city: Salt Lake City
country: United States
state: Utah
city: Milwaukee
country: United States
state: Wisconsin
city: Buenos Aires
country: Argentina
state: Ciudad Auton. de Buenos Aires
city: Rosario
country: Argentina
state: Santa Fe
city: Plovdiv
country: Bulgaria
city: Sofia
country: Bulgaria
city: Varna
country: Bulgaria
city: Timisoara
country: Romania
state: Timis
city: Brasov
country: Romania
city: Bucharest
country: Romania
city: Bucharest
country: Romania
city: Constanta
country: Romania
Study officials:
affiliation: Bayer
name: Bayer Study Director
role: STUDY_DIRECTOR
References:
citation: Manco-Johnson MJ, Kempton CL, Reding MT, Lissitchkov T, Goranov S, Gercheva L, Rusen L, Ghinea M, Uscatescu V, Rescia V, Hong W. Randomized, controlled, parallel-group trial of routine prophylaxis vs. on-demand treatment with sucrose-formulated recombinant factor VIII in adults with severe hemophilia A (SPINART). J Thromb Haemost. 2013 Jun;11(6):1119-27. doi: 10.1111/jth.12202.
citation: Manco-Johnson MJ, Lundin B, Funk S, Peterfy C, Raunig D, Werk M, Kempton CL, Reding MT, Goranov S, Gercheva L, Rusen L, Uscatescu V, Pierdominici M, Engelen S, Pocoski J, Walker D, Hong W. Effect of late prophylaxis in hemophilia on joint status: a randomized trial. J Thromb Haemost. 2017 Nov;15(11):2115-2124. doi: 10.1111/jth.13811. Epub 2017 Oct 10.