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

NCT ID: NCT00623480

Last Updated: 2014-11-17

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

84 participants

Study Classification

INTERVENTIONAL

Study Start Date

2008-03-31

Study Completion Date

2013-11-30

Brief Summary

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

Detailed Description

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Conditions

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Hemophilia A

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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.

Group Type EXPERIMENTAL

Recombinant Factor VIII (Kogenate FS, BAY14-2222)

Intervention Type BIOLOGICAL

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.

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.

Group Type EXPERIMENTAL

Recombinant Factor VIII (Kogenate FS, BAY14-2222)

Intervention Type BIOLOGICAL

Treated according to the Kogenate FS package insert indications and study physician recommendations

Interventions

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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.

Intervention Type BIOLOGICAL

Recombinant Factor VIII (Kogenate FS, BAY14-2222)

Treated according to the Kogenate FS package insert indications and study physician recommendations

Intervention Type BIOLOGICAL

Eligibility Criteria

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Inclusion Criteria

* Males aged 12 to 50 years (US and Argentina)
* Males aged 18 to 50 years (other countries)
* 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
Minimum Eligible Age

12 Years

Maximum Eligible Age

50 Years

Eligible Sex

MALE

Accepts Healthy Volunteers

No

Sponsors

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Bayer

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Bayer Study Director

Role: STUDY_DIRECTOR

Bayer

Locations

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Tucson, Arizona, United States

Site Status

Little Rock, Arkansas, United States

Site Status

Orange, California, United States

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Sacramento, California, United States

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Aurora, Colorado, United States

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Washington D.C., District of Columbia, United States

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Orlando, Florida, United States

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Atlanta, Georgia, United States

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Chicago, Illinois, United States

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Chicago, Illinois, United States

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Indianapolis, Indiana, United States

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Iowa City, Iowa, United States

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Louisville, Kentucky, United States

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Boston, Massachusetts, United States

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Detroit, Michigan, United States

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Minneapolis, Minnesota, United States

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Kansas City, Missouri, United States

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Las Vegas, Nevada, United States

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Newark, New Jersey, United States

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New York, New York, United States

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New York, New York, United States

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Cleveland, Ohio, United States

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Hershey, Pennsylvania, United States

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Pittsburgh, Pennsylvania, United States

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Knoxville, Tennessee, United States

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Houston, Texas, United States

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Salt Lake City, Utah, United States

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Milwaukee, Wisconsin, United States

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Buenos Aires, Ciudad Auton. de Buenos Aires, Argentina

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Rosario, Santa Fe Province, Argentina

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Plovdiv, , Bulgaria

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Sofia, , Bulgaria

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Varna, , Bulgaria

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Timișoara, Timiș County, Romania

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Brasov, , Romania

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Bucharest, , Romania

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Bucharest, , Romania

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Constanța, , Romania

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Countries

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United States Argentina Bulgaria Romania

References

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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.

Reference Type RESULT
PMID: 23528101 (View on PubMed)

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.

Reference Type DERIVED
PMID: 28836341 (View on PubMed)

Other Identifiers

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2008-000985-21

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

12800

Identifier Type: -

Identifier Source: org_study_id