Safety Study of Alphanate in Previously Treated Patients With Severe Hemophilia A

Study Overview
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Brief Summary
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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
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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.

Official Title
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Phase IV A Study of Immunologic Safety for Alphanate in Previously Treated Patients Diagnosed With Severe Hemophilia A

Conditions
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Severe Hemophilia A

Intervention / Treatment
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* Drug: Alphanate SD/HT


Participation Criteria
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Eligibility Criteria
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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).

Ages Eligible for Study
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Minimum Age: 6 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Coagulation factor VIII (Human)<br>Anti-Hemophilic coagulation factor VIII (Human) Alphanate SD/HT | Drug: Alphanate SD/HT<br>* Plasma-derived preparation of Factor VIII<br>* Other names: Anti-hemophilic (human) coagulation factor VIII;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Factor VIII (FVIII) Inhibitor Development | Incidence of FVIII inhibitor development was defined as any result determined positive at a central laboratory (inhibitor titer of greater than 0.6 modified Bethesda Units/milliliters [BU/mL]) using Nijmegen modification of the Bethesda assay. | Up to Month 30 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Adverse Events (AE) | An AE is defined as any untoward medical occurrence in a participant or clinical investigation participant administered a medicinal product or study treatment, and which did not necessarily have a causal relationship with this administration. Here end of study is defined as completion/discontinuation visit. | Up to Month 30 | 
| Change From Baseline in Alkaline Phosphatase | The Baseline value was the last non-missing value before study drug was taken and end of study was defined as completion/discontinuation visit. Change from Baseline was calculated by subtracting Baseline value from the post-infusion visit value. | 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) | 
| Change From Baseline in Alanine Aminotransferase | The Baseline value was the last non-missing value before study drug was taken and end of study was defined as completion/discontinuation visit. Change from Baseline was calculated by subtracting Baseline value from the post-infusion visit value. | 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) | 
| Change From Baseline in Aspartate Aminotransferase | The Baseline value was the last non-missing value before study drug was taken and end of study was defined as completion/discontinuation visit. Change from Baseline was calculated by subtracting Baseline value from the post-infusion visit value. | 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) | 
| Change From Baseline in Lactate Dehydrogenase | The Baseline value was the last non-missing value before study drug was taken and end of study was defined as completion/discontinuation visit. Change from Baseline was calculated by subtracting Baseline value from the post-infusion visit value. | 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) | 
| Change From Baseline in Bilirubin | The Baseline value was the last non-missing value before study drug was taken and end of study was defined as completion/discontinuation visit. Change from Baseline was calculated by subtracting Baseline value from the post-infusion visit value. | 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) | 
| Change From Baseline in Blood Urea Nitrogen | The Baseline value was the last non-missing value before study drug was taken and end of study was defined as completion/discontinuation visit. Change from Baseline was calculated by subtracting Baseline value from the post-infusion visit value. | 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) | 
| Change From Baseline in Creatinine | The Baseline value was the last non-missing value before study drug was taken and end of study was defined as completion/discontinuation visit. Change from Baseline was calculated by subtracting Baseline value from the post-infusion visit value. | 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) | 
| 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 | Seroconversion based on Enzyme-linked Immunosorbent Assay (ELISA). Seronegative defined as non-reactive in an ELISA test for antibody to the virus in question. Seropositive defined as reactive in an ELISA test for antibody to the virus in question. | Up to Month 30 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hemophilia A, Plasma-derived treatment, Factor VIII, Inhibitor