Clinical trial NCT00323856: Safety Study of Alphanate in Previously Treated Patients With Severe Hemophilia A
Official title: Phase IV A Study of Immunologic Safety for Alphanate in Previously Treated Patients Diagnosed With Severe Hemophilia A
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Severe Hemophilia A
Keywords: Hemophilia A
Plasma-derived treatment
Factor VIII
Inhibitor
Lead sponsor: Grifols Biologicals, LLC
Sponsor class: INDUSTRY
First posted: 2006-05-10
Enrollment: 51
Sex: MALE
Minimum age (years): 6
Maximum age (years): 65
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to determine the immunologic and overall safety associated with long-term use of Alphanate in subjects diagnosed with severe hemophilia A (Factor VIII:C less than 0.01 IU/ml), who have been previously treated with plasma-derived Factor VIII products other than Alphanate and who have no history of developing either antibody inhibitors to Factor VIII or nonspecific inhibitors of coagulation.

Detailed description: This is a Phase IV, non-randomized, multicenter study of at least 50 evaluable subjects diagnosed with severe hemophilia A. Enrolled subjects will be treated at home and with in-clinic therapy exclusively with Alphanate as their sole source of Factor VIII concentrate for prophylaxis and treatment of all bleeding episodes and surgical procedures. Subjects will be treated for at least 2 years and a minimum of 50 exposure days, or if 50 exposure days are not reached, for a maximum of 30 months and in accordance with the subject's usual pre-study treatment regimen. Subjects will continue treatment as above or until they develop inhibitors to Factor VIII at a titer greater than or equal to 5 Bethesda units (BU/ml); Factor VIII becomes ineffective at providing hemostasis, or the subject exhibits severe or serious adverse events that prevent completion of the study.

Eligibility criteria: Inclusion Criteria:

* Male.
* At least 6 years of age and not more than 65 years of age.
* Signed and dated Informed Consent Form and Patient Authorization for Release of Information approved by the appropriate Institutional Review Board (IRB) prior to screening and enrollment. If the subject is a minor (i.e., less than 18 years of age) both he and his parent or legal guardian must sign and date the informed consent.
* Diagnosis of severe hemophilia A.
* Levels of Factor VIII less than 0.01 IU/mL.
* Treatment with cryoprecipitate, Factor VIII concentrates, and/or whole blood, for at least 150 cumulative exposure days (CEDs) prior to enrollment.
* No treatment with cryoprecipitate, Factor VIII concentrate, or any other blood product, for at least 72 hours prior to screening.
* No previous diagnosis with inhibitors to Factor VIII at any detectable titer.
* Subjects must never have been diagnosed with nonspecific inhibitors of coagulation.
* Negative test for the presence of Factor VIII inhibitors at screening and enrollment.
* CD4 counts greater than or equal to 400 cells/µL.
* Vaccination against hepatitis A and hepatitis B, or evidence of antibodies against hepatitis A and hepatitis B. (A subject who has no prior immunity against hepatitis A will be offered a course of vaccination for hepatitis A).
* Karnofsky Performance Score of at least 50.

Exclusion Criteria:

* Any immunosuppressive medications including intravenous immunoglobulins at the time of enrollment.
* Clinical signs or symptoms of an infection, such as fever, chills or nausea during screening or enrollment.
* History of frequent reactions to Factor VIII concentrates (e.g., chills or headaches).
* Prior treatment with Alphanate® (Solvent-Detergent/ Heat-Treated).
* Immunocompromised (including HIV+ status or has an impaired immune system due to disease or treatment).

Primary outcomes:
measure: Number of Participants With Factor VIII (FVIII) Inhibitor Development
timeFrame: Up to Month 30
Secondary outcomes:
measure: Number of Participants With Adverse Events (AE)
timeFrame: Up to Month 30
measure: Change From Baseline in Alkaline Phosphatase
timeFrame: Baseline and Quarterly Visit 1 (Month 3), 2 (Month 6), 3 (Month 9), 4 (Month 12), 5 (Month 15), 6 (Month 18), 7 (Month 21), 8 (Month 24), 9 (Month 27) and 10 (Month 30)
measure: Change From Baseline in Alanine Aminotransferase
timeFrame: Baseline and Quarterly Visit 1 (Month 3), 2 (Month 6), 3 (Month 9), 4 (Month 12), 5 (Month 15), 6 (Month 18), 7 (Month 21), 8 (Month 24), 9 (Month 27) and 10 (Month 30)
measure: Change From Baseline in Aspartate Aminotransferase
timeFrame: Baseline and Quarterly Visit 1 (Month 3), 2 (Month 6), 3 (Month 9), 4 (Month 12), 5 (Month 15), 6 (Month 18), 7 (Month 21), 8 (Month 24), 9 (Month 27) and 10 (Month 30)
measure: Change From Baseline in Lactate Dehydrogenase
timeFrame: Baseline and Quarterly Visit 1 (Month 3), 2 (Month 6), 3 (Month 9), 4 (Month 12), 5 (Month 15), 6 (Month 18), 7 (Month 21), 8 (Month 24), 9 (Month 27) and 10 (Month 30)
measure: Change From Baseline in Bilirubin
timeFrame: Baseline and Quarterly Visit 1 (Month 3), 2 (Month 6), 3 (Month 9), 4 (Month 12), 5 (Month 15), 6 (Month 18), 7 (Month 21), 8 (Month 24), 9 (Month 27) and 10 (Month 30)
measure: Change From Baseline in Blood Urea Nitrogen
timeFrame: Baseline and Quarterly Visit 1 (Month 3), 2 (Month 6), 3 (Month 9), 4 (Month 12), 5 (Month 15), 6 (Month 18), 7 (Month 21), 8 (Month 24), 9 (Month 27) and 10 (Month 30)
measure: Change From Baseline in Creatinine
timeFrame: Baseline and Quarterly Visit 1 (Month 3), 2 (Month 6), 3 (Month 9), 4 (Month 12), 5 (Month 15), 6 (Month 18), 7 (Month 21), 8 (Month 24), 9 (Month 27) and 10 (Month 30)
measure: Number of Participants Human Immunodeficiency Virus Type 1 and 2 (HIV-1/HIV-2), Hepatitis A Virus (HAV), Hepatitis B Virus (HBV), Hepatitis C Virus (HCV) or Parvovirus B19 -Negative at Baseline Who Are Seropositive for Any of These Viruses
timeFrame: Up to Month 30
Other outcomes:
Locations:
city: Poznan
country: Poland
facility: Oddzial Chorob Wewnetrznych i Hematologii
state: Szkolna
city: Krakow
country: Poland
facility: Katedra i Klinika Hematologii Collegium Medicum UJ
Study officials:
affiliation: Instituto Grifols SA
name: Michael Ken Woodward
role: STUDY_DIRECTOR
References: