Try our beta test site
IMPORTANT: Listing of a study on this site does not reflect endorsement by the National Institutes of Health. Talk with a trusted healthcare professional before volunteering for a study. Read more...

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 (SPINART)

This study has been completed.
Information provided by (Responsible Party):
Bayer Identifier:
First received: February 4, 2008
Last updated: November 5, 2014
Last verified: November 2014
To evaluate the effect of secondary prophylaxis as compared to episodic treatment on bleeding frequency (number of bleeds per year) and on joint damage.

Condition Intervention Phase
Hemophilia A
Biological: Recombinant Factor VIII (Kogenate FS, BAY14-2222)
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: 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

Resource links provided by NLM:

Further study details as provided by Bayer:

Primary Outcome Measures:
  • Bleeding Frequency (Number of Total Bleeds) [ Time Frame: 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 Outcome Measures:
  • Change From Baseline to 3 Years in the MRI (Magnetic Resonance Imaging) Scale. [ Time Frame: Baseline and 3 years ]
    The Extended MRI Scale total score has a range between 0 (normal unaffected joint) to 45 (maximal joint damage) points. It is composed of 2 domains, the soft tissue domain with a maximum of 9 points and the osteochondral domain with a maximum of 36 points. A single score for each subject was to be calculated from the sum of both domains and the average over all joints for the Extended MRI endpoint. Higher MRI score denotes greater joint structure damage thus a positive change from baseline means worsening.

  • Change From Baseline to 3 Years in the Colorado Adult Joint Assessment Scale [ Time Frame: Baseline and 3 years ]
    The total joint score is derived for each of six joints: left and right sides for knees (score: 0-25), ankles (score: 0-25), and elbows (score: 0-21). Higher CAJAS (Colorado Adult Joint Assessment Scale) score denotes greater joint structure damage thus a positive change from baseline means worsening. CAJAS total score is the sum of all 6 joints, ranging from 0 (best possible outcome) to 142 (worst possible outcome).

Other Outcome Measures:
  • Change From Baseline to 3 Years in the Physical Functioning Domain of the Haemo-QoL-A [ Time Frame: Baseline and 3 years ]
    The Haemo-QoL-A total score as well as each of its domains have a range between 0 (worst Quality of Life) and 100 (best Quality of Life) points. Therefore, a higher Haemo-QoL-A score denotes greater Quality of Life.

Enrollment: 84
Study Start Date: March 2008
Study Completion Date: November 2013
Primary Completion Date: September 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Recombinant Factor VIII prophylaxis treatment
Participants received 25 IU/kg of Recombinant Factor VIII (Kogenate FS, BAY14-2222) intravenously (IV), 3 times per week. Dose escalation steps by 5 IU/kg (to 30 IU/kg or 35 IU/kg maximum) for patients exhibiting a bleeding frequency of 12 bleeding episodes per year or greater.
Biological: Recombinant Factor VIII (Kogenate FS, BAY14-2222)
Prophylaxis treatment includes three times per week administration of 25 IU/kg of Kogenate FS. Dose escalation steps by 5 IU/kg (to 30 IU/kg or 35 IU/kg maximum) exhibiting a bleeding frequency of 12 bleeding episodes per year or greater.
Experimental: Recombinant Factor VIII on-demand treatment
Participants received Recombinant Factor VIII (Kogenate FS, BAY14-2222) IV for bleeds in accordance with package insert instructions and study physician recommendations.
Biological: Recombinant Factor VIII (Kogenate FS, BAY14-2222)
Treated according to the Kogenate FS package insert indications and study physician recommendations


Ages Eligible for Study:   12 Years to 50 Years   (Child, Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its identifier: NCT00623480

  Hide Study Locations
United States, Arizona
Tucson, Arizona, United States, 85724
United States, Arkansas
Little Rock, Arkansas, United States, 72202
United States, California
Orange, California, United States, 92868
Sacramento, California, United States, 95817
United States, Colorado
Aurora, Colorado, United States, 80045
United States, District of Columbia
Washington, District of Columbia, United States, 20007-2197
United States, Florida
Orlando, Florida, United States, 32801
United States, Georgia
Atlanta, Georgia, United States, 30322
United States, Illinois
Chicago, Illinois, United States, 60611
Chicago, Illinois, United States, 60612
United States, Indiana
Indianapolis, Indiana, United States, 46260
United States, Iowa
Iowa City, Iowa, United States, 52242-1089
United States, Kentucky
Louisville, Kentucky, United States, 40202
United States, Massachusetts
Boston, Massachusetts, United States, 02115
United States, Michigan
Detroit, Michigan, United States, 48201-2196
United States, Minnesota
Minneapolis, Minnesota, United States, 55455
United States, Missouri
Kansas City, Missouri, United States, 64108
United States, Nevada
Las Vegas, Nevada, United States, 89109-2803
United States, New Jersey
Newark, New Jersey, United States, 07112
United States, New York
New York, New York, United States, 10029
New York, New York, United States, 10065
United States, Ohio
Cleveland, Ohio, United States, 44106
United States, Pennsylvania
Hershey, Pennsylvania, United States, 17033-0850
Pittsburgh, Pennsylvania, United States, 15213
United States, Tennessee
Knoxville, Tennessee, United States, 37920
United States, Texas
Houston, Texas, United States, 77030
United States, Utah
Salt Lake City, Utah, United States, 84132
United States, Wisconsin
Milwaukee, Wisconsin, United States, 53226
Buenos Aires, Ciudad Auton. de Buenos Aires, Argentina, C1221 ADC
Rosario, Santa Fe, Argentina, S2000CKF
Plovdiv, Bulgaria, 4002
Sofia, Bulgaria, 1756
Varna, Bulgaria, 9010
Timisoara, Timis, Romania, 300011
Brasov, Romania, 50035
Bucharest, Romania, 022328
Bucharest, Romania, 11026
Constanta, Romania, 900591
Sponsors and Collaborators
Study Director: Bayer Study Director Bayer
  More Information

Additional Information:
Responsible Party: Bayer Identifier: NCT00623480     History of Changes
Other Study ID Numbers: 12800
2008-000985-21 ( EudraCT Number )
Study First Received: February 4, 2008
Results First Received: May 2, 2013
Last Updated: November 5, 2014

Keywords provided by Bayer:
Hemophilia A

Additional relevant MeSH terms:
Hemophilia A
Blood Coagulation Disorders, Inherited
Blood Coagulation Disorders
Hematologic Diseases
Coagulation Protein Disorders
Hemorrhagic Disorders
Genetic Diseases, Inborn
Factor VIII
Coagulants processed this record on April 28, 2017