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

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

Status

Completed

Phases

Phase 4

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT00323856

Enrollment

Registered

2006-05-10

Start date

2003-04-08

Completion date

2018-12-14

Last updated

2025-01-16

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Severe Hemophilia A

Keywords

Hemophilia A, Plasma-derived treatment, Factor VIII, Inhibitor

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.

Interventions

DRUGAlphanate SD/HT

Plasma-derived preparation of Factor VIII

Study design

Allocation

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

MALE

Age

6 Years to 65 Years

Healthy volunteers

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).

Design outcomes

Primary

Measure	Time frame	Description
Number of Participants With Factor VIII (FVIII) Inhibitor Development	Up to Month 30	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.

Secondary

Measure	Time frame	Description
Change From Baseline in Alkaline Phosphatase	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)	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.
Change From Baseline in Alanine Aminotransferase	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)	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.
Change From Baseline in Aspartate Aminotransferase	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)	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.
Change From Baseline in Lactate Dehydrogenase	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)	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.
Number of Participants With Adverse Events (AE)	Up to Month 30	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.
Change From Baseline in Blood Urea Nitrogen	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)	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.
Change From Baseline in Creatinine	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)	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.
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	Up to Month 30	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.
Change From Baseline in Bilirubin	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)	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.

Countries

Poland

Participant flow

Recruitment details

This study was conducted in Poland at 2 centers from April 8, 2003 to December 14, 2018.

Pre-assignment details

Male participants diagnosed with severe hemophilia A who have been previously treated with Factor VIII concentrates, cryoprecipitate, or whole blood for a total of 150 cumulative exposure were enrolled. A total of 51 participants were enrolled out of which, 50 participants received the treatment. A total of 45 participants completed the study.

Participants by arm

Arm	Count
Alphanate Participants were treated at home and with in-clinic therapy exclusively with Alphanate as their sole source of Factor VIII (FVIII) concentrate for prophylaxis and treatment of all bleeding episodes and surgical procedures for a period of at least two years and a minimum of 50 exposure days, or, if 50 exposure days were not reached, for a maximum of 30 months. An exposure day was defined as any day on which a participant received one or more infusions of any FVIII containing product. Alphanate was administered intravascularly in accordance with the participant's usual pre-study treatment regimen.	50
Total	50

Arm

Count

Alphanate

Participants were treated at home and with in-clinic therapy exclusively with Alphanate as their sole source of Factor VIII (FVIII) concentrate for prophylaxis and treatment of all bleeding episodes and surgical procedures for a period of at least two years and a minimum of 50 exposure days, or, if 50 exposure days were not reached, for a maximum of 30 months. An exposure day was defined as any day on which a participant received one or more infusions of any FVIII containing product. Alphanate was administered intravascularly in accordance with the participant's usual pre-study treatment regimen.

Total

Withdrawals & dropouts

Period	Reason	FG000
Overall Study	Missing	2
Overall Study	Reason not specified	1
Overall Study	Was uncooperative and noncompliant	1
Overall Study	Withdrawal by Subject	1

Baseline characteristics

Characteristic	Alphanate
Age, Continuous	24.8 years STANDARD_DEVIATION 14.45
Race/Ethnicity, Customized Asian	11 participants
Race/Ethnicity, Customized Caucasian	30 participants
Race/Ethnicity, Customized Hispanic	8 participants
Race/Ethnicity, Customized Other	1 participants
Sex: Female, Male Female	0 Participants
Sex: Female, Male Male	50 Participants
Subjects with antibody inhibitors to FVIII	0 Participants

Adverse events

Event type	EG000 affected / at risk
deaths Total, all-cause mortality	0 / 50
other Total, other adverse events	22 / 50
serious Total, serious adverse events	4 / 50

Outcome results

Primary

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.

Time frame: Up to Month 30

Population: Safety population included all participants who received at least one infusion of study medication.

Arm	Measure	Value (COUNT_OF_PARTICIPANTS)
Alphanate	Number of Participants With Factor VIII (FVIII) Inhibitor Development	0 Participants

Secondary

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.