Trial Outcomes & Findings for Safety Study of Alphanate in Previously Treated Patients With Severe Hemophilia A (NCT NCT00323856)

NCT ID: NCT00323856

Last Updated: 2025-01-16

Results Overview

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.

• Recruitment status: COMPLETED
• Study phase: PHASE4
• Target enrollment: 51 participants
• Primary outcome timeframe: Up to Month 30
• Results posted on: 2025-01-16

Participant Flow

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

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.

Participant milestones

Measure	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.
Overall Study STARTED	50
Overall Study COMPLETED	45
Overall Study NOT COMPLETED	5

Reasons for withdrawal

Measure	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.
Overall Study Withdrawal by Subject	1
Overall Study Was uncooperative and noncompliant	1
Overall Study Reason not specified	1
Overall Study Missing	2

Baseline Characteristics

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

Baseline characteristics by cohort

Measure	Alphanate n=50 Participants 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.
Age, Continuous	24.8 years STANDARD_DEVIATION 14.45 • n=5 Participants
Sex: Female, Male Female	0 Participants n=5 Participants
Sex: Female, Male Male	50 Participants n=5 Participants
Race/Ethnicity, Customized Caucasian	30 participants n=5 Participants
Race/Ethnicity, Customized Hispanic	8 participants n=5 Participants
Race/Ethnicity, Customized Asian	11 participants n=5 Participants
Race/Ethnicity, Customized Other	1 participants n=5 Participants
Subjects with antibody inhibitors to FVIII	0 Participants n=5 Participants

PRIMARY outcome

Timeframe: Up to Month 30

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

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.

Outcome measures

Measure

Alphanate n=50 Participants 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.

Number of Participants With Factor VIII (FVIII) Inhibitor Development

0 Participants

SECONDARY outcome

Timeframe: Up to Month 30

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

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.

Outcome measures

Measure

Alphanate n=50 Participants 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.

Number of Participants With Adverse Events (AE)

30 Participants

SECONDARY outcome

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)

Population: Safety population included all participants who received at least one infusion of study medication. Number analyzed signifies number of participants evaluable at each specified timepoint.

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.

Outcome measures

Measure	Alphanate n=50 Participants 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.
Change From Baseline in Alkaline Phosphatase Baseline	2.315 microkatal per liter (μkat/L) Standard Deviation 1.3287
Change From Baseline in Alkaline Phosphatase Change at Quarterly Visit 1 (Month 3)	-0.030 microkatal per liter (μkat/L) Standard Deviation 0.6136
Change From Baseline in Alkaline Phosphatase Change at Quarterly Visit 2 (Month 6)	-0.146 microkatal per liter (μkat/L) Standard Deviation 0.8197
Change From Baseline in Alkaline Phosphatase Change at Quarterly Visit 3 (Month 9)	-0.087 microkatal per liter (μkat/L) Standard Deviation 0.8601
Change From Baseline in Alkaline Phosphatase Change at Quarterly Visit 4 (Month 12)	-0.309 microkatal per liter (μkat/L) Standard Deviation 0.7635
Change From Baseline in Alkaline Phosphatase Change at Quarterly Visit 5 (Month 15)	-0.127 microkatal per liter (μkat/L) Standard Deviation 1.0940
Change From Baseline in Alkaline Phosphatase Change at Quarterly Visit 6 (Month 18)	-0.342 microkatal per liter (μkat/L) Standard Deviation 0.9484
Change From Baseline in Alkaline Phosphatase Change at Quarterly Visit 7 (Month 21)	-0.490 microkatal per liter (μkat/L) Standard Deviation 1.0561
Change From Baseline in Alkaline Phosphatase Change at Quarterly Visit 8 (Month 24)	-0.299 microkatal per liter (μkat/L) Standard Deviation 1.2843
Change From Baseline in Alkaline Phosphatase Change at Quarterly Visit 9 (Month 27)	-1.004 microkatal per liter (μkat/L) Standard Deviation 1.2453
Change From Baseline in Alkaline Phosphatase Change at Quarterly Visit 10 (Month 30)	-0.075 microkatal per liter (μkat/L) Standard Deviation 0.0827

SECONDARY outcome

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)

Population: Safety population included all participants who received at least one infusion of study medication. Number analyzed signifies number of participants evaluable at each specified timepoint

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.

Outcome measures

Measure	Alphanate n=50 Participants 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.
Change From Baseline in Alanine Aminotransferase Baseline	0.577 μkat/L Standard Deviation 0.6770
Change From Baseline in Alanine Aminotransferase Change at Quarterly Visit 1 (Month 3)	-0.005 μkat/L Standard Deviation 0.2437
Change From Baseline in Alanine Aminotransferase Change at Quarterly Visit 2 (Month 6)	-0.055 μkat/L Standard Deviation 0.2754
Change From Baseline in Alanine Aminotransferase Change at Quarterly Visit 3 (Month 9)	-0.089 μkat/L Standard Deviation 0.3625
Change From Baseline in Alanine Aminotransferase Change at Quarterly Visit 4 (Month 12)	-0.114 μkat/L Standard Deviation 0.4310
Change From Baseline in Alanine Aminotransferase Change at Quarterly Visit 5 (Month 15)	-0.081 μkat/L Standard Deviation 0.3539
Change From Baseline in Alanine Aminotransferase Change at Quarterly Visit 6 (Month 18)	-0.133 μkat/L Standard Deviation 0.4109
Change From Baseline in Alanine Aminotransferase Change at Quarterly Visit 7 (Month 21)	-0.117 μkat/L Standard Deviation 0.3861
Change From Baseline in Alanine Aminotransferase Change at Quarterly Visit 8 (Month 24)	-0.077 μkat/L Standard Deviation 0.3951
Change From Baseline in Alanine Aminotransferase Change at Quarterly Visit 9 (Month 27)	-0.074 μkat/L Standard Deviation 0.1730
Change From Baseline in Alanine Aminotransferase Change at Quarterly Visit 10 (Month 30)	-0.150 μkat/L Standard Deviation 0.2688

SECONDARY outcome

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)

Population: Safety population included all participants who received at least one infusion of study medication. Number analyzed signifies number of participants evaluable at each specified timepoint.

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.

Outcome measures

Measure	Alphanate n=50 Participants 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.
Change From Baseline in Aspartate Aminotransferase Baseline	0.544 μkat/L Standard Deviation 0.6337
Change From Baseline in Aspartate Aminotransferase Change at Quarterly Visit 1 (Month 3)	0.023 μkat/L Standard Deviation 0.1312
Change From Baseline in Aspartate Aminotransferase Change at Quarterly Visit 2 (Month 6)	-0.011 μkat/L Standard Deviation 0.2900
Change From Baseline in Aspartate Aminotransferase Change at Quarterly Visit 3 (Month 9)	-0.062 μkat/L Standard Deviation 0.3885
Change From Baseline in Aspartate Aminotransferase Change at Quarterly Visit 4 (Month 12)	-0.092 μkat/L Standard Deviation 0.4350
Change From Baseline in Aspartate Aminotransferase Change at Quarterly Visit 5 (Month 15)	-0.071 μkat/L Standard Deviation 0.3890
Change From Baseline in Aspartate Aminotransferase Change at Quarterly Visit 6 (Month 18)	-0.081 μkat/L Standard Deviation 0.4083
Change From Baseline in Aspartate Aminotransferase Change at Quarterly Visit 7 (Month 21)	-0.074 μkat/L Standard Deviation 0.3769
Change From Baseline in Aspartate Aminotransferase Change at Quarterly Visit 8 (Month 24)	-0.020 μkat/L Standard Deviation 0.3913
Change From Baseline in Aspartate Aminotransferase Change at Quarterly Visit 9 (Month 27)	-0.043 μkat/L Standard Deviation 0.0963
Change From Baseline in Aspartate Aminotransferase Change at Quarterly Visit 10 (Month 30)	-0.039 μkat/L Standard Deviation 0.0632

SECONDARY outcome

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)

Population: Safety population included all participants who received at least one infusion of study medication. Number analyzed signifies number of participants evaluable at each specified timepoint.

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.

Outcome measures

Measure	Alphanate n=50 Participants 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.
Change From Baseline in Lactate Dehydrogenase Baseline	5.64 μkat/L Standard Deviation 2.089
Change From Baseline in Lactate Dehydrogenase Change at Quarterly Visit 1 (Month 3)	-0.07 μkat/L Standard Deviation 0.926
Change From Baseline in Lactate Dehydrogenase Change at Quarterly Visit 2 (Month 6)	-0.04 μkat/L Standard Deviation 1.703
Change From Baseline in Lactate Dehydrogenase Change at Quarterly Visit 3 (Month 9)	-0.01 μkat/L Standard Deviation 1.595
Change From Baseline in Lactate Dehydrogenase Change at Quarterly Visit 4 (Month 12)	-0.31 μkat/L Standard Deviation 2.231
Change From Baseline in Lactate Dehydrogenase Change at Quarterly Visit 5 (Month 15)	-0.47 μkat/L Standard Deviation 1.388
Change From Baseline in Lactate Dehydrogenase Change at Quarterly Visit 6 (Month 18)	-0.52 μkat/L Standard Deviation 1.814
Change From Baseline in Lactate Dehydrogenase Change at Quarterly Visit 7 (Month 21)	-0.65 μkat/L Standard Deviation 1.560
Change From Baseline in Lactate Dehydrogenase Change at Quarterly Visit 8 (Month 24)	-0.21 μkat/L Standard Deviation 2.413
Change From Baseline in Lactate Dehydrogenase Change at Quarterly Visit 9 (Month 27)	-0.21 μkat/L Standard Deviation 1.497
Change From Baseline in Lactate Dehydrogenase Change at Quarterly Visit 10 (Month 30)	0.22 μkat/L Standard Deviation 0.972

SECONDARY outcome

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)

Population: Safety population included all participants who received at least one infusion of study medication. Number analyzed signifies number of participants evaluable at each specified timepoint.

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.

Outcome measures

Measure	Alphanate n=50 Participants 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.
Change From Baseline in Bilirubin Baseline	12.346 micromole per liter (μmol/L) Standard Deviation 6.2515
Change From Baseline in Bilirubin Change at Quarterly Visit 1 (Month 3)	41.387 micromole per liter (μmol/L) Standard Deviation 255.8005
Change From Baseline in Bilirubin Change at Quarterly Visit 2 (Month 6)	-0.815 micromole per liter (μmol/L) Standard Deviation 5.0952
Change From Baseline in Bilirubin Change at Quarterly Visit 3 (Month 9)	40.485 micromole per liter (μmol/L) Standard Deviation 253.2611
Change From Baseline in Bilirubin Change at Quarterly Visit 4 (Month 12)	1.461 micromole per liter (μmol/L) Standard Deviation 7.2030
Change From Baseline in Bilirubin Change at Quarterly Visit 5 (Month 15)	-0.031 micromole per liter (μmol/L) Standard Deviation 4.0146
Change From Baseline in Bilirubin Change at Quarterly Visit 6 (Month 18)	0.759 micromole per liter (μmol/L) Standard Deviation 4.0038
Change From Baseline in Bilirubin Change at Quarterly Visit 7 (Month 21)	0.498 micromole per liter (μmol/L) Standard Deviation 5.3277
Change From Baseline in Bilirubin Change at Quarterly Visit 8 (Month 24)	0.060 micromole per liter (μmol/L) Standard Deviation 4.4453
Change From Baseline in Bilirubin Change at Quarterly Visit 9 (Month 27)	0.760 micromole per liter (μmol/L) Standard Deviation 2.9257
Change From Baseline in Bilirubin Change at Quarterly Visit 10 (Month 30)	-1.539 micromole per liter (μmol/L) Standard Deviation 3.8664

SECONDARY outcome

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)

Population: Safety population included all participants who received at least one infusion of study medication. Number analyzed signifies number of participants evaluable at each specified timepoint.

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.

Outcome measures

Measure	Alphanate n=50 Participants 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.
Change From Baseline in Blood Urea Nitrogen Change at Quarterly Visit 9 (Month 27)	0.728 millimole per liter (mmol/L) Standard Deviation 1.4505
Change From Baseline in Blood Urea Nitrogen Change at Quarterly Visit 7 (Month 21)	0.766 millimole per liter (mmol/L) Standard Deviation 2.2935
Change From Baseline in Blood Urea Nitrogen Change at Quarterly Visit 8 (Month 24)	0.907 millimole per liter (mmol/L) Standard Deviation 2.7810
Change From Baseline in Blood Urea Nitrogen Baseline	5.330 millimole per liter (mmol/L) Standard Deviation 2.8786
Change From Baseline in Blood Urea Nitrogen Change at Quarterly Visit 1 (Month 3)	0.140 millimole per liter (mmol/L) Standard Deviation 1.8371
Change From Baseline in Blood Urea Nitrogen Change at Quarterly Visit 2 (Month 6)	0.177 millimole per liter (mmol/L) Standard Deviation 1.8985
Change From Baseline in Blood Urea Nitrogen Change at Quarterly Visit 3 (Month 9)	0.489 millimole per liter (mmol/L) Standard Deviation 2.1387
Change From Baseline in Blood Urea Nitrogen Change at Quarterly Visit 4 (Month 12)	1.356 millimole per liter (mmol/L) Standard Deviation 5.6452
Change From Baseline in Blood Urea Nitrogen Change at Quarterly Visit 5 (Month 15)	13.476 millimole per liter (mmol/L) Standard Deviation 79.9256
Change From Baseline in Blood Urea Nitrogen Change at Quarterly Visit 6 (Month 18)	1.331 millimole per liter (mmol/L) Standard Deviation 3.6889
Change From Baseline in Blood Urea Nitrogen Change at Quarterly Visit 10 (Month 30)	0.119 millimole per liter (mmol/L) Standard Deviation 2.0300

SECONDARY outcome

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)

Population: Safety population included all participants who received at least one infusion of study medication.Number analyzed signifies number of participants evaluable at each specified timepoint.

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.

Outcome measures

Measure	Alphanate n=50 Participants 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.
Change From Baseline in Creatinine Baseline	61.30 micromole per liter (μmol/L) Standard Deviation 15.067
Change From Baseline in Creatinine Change at Quarterly Visit 1 (Month 3)	3.47 micromole per liter (μmol/L) Standard Deviation 21.125
Change From Baseline in Creatinine Change at Quarterly Visit 2 (Month 6)	-1.76 micromole per liter (μmol/L) Standard Deviation 12.956
Change From Baseline in Creatinine Change at Quarterly Visit 3 (Month 9)	4.18 micromole per liter (μmol/L) Standard Deviation 13.627
Change From Baseline in Creatinine Change at Quarterly Visit 4 (Month 12)	18.56 micromole per liter (μmol/L) Standard Deviation 111.453
Change From Baseline in Creatinine Change at Quarterly Visit 5 (Month 15)	5.80 micromole per liter (μmol/L) Standard Deviation 18.984
Change From Baseline in Creatinine Change at Quarterly Visit 6 (Month 18)	5.44 micromole per liter (μmol/L) Standard Deviation 15.480
Change From Baseline in Creatinine Change at Quarterly Visit 7 (Month 21)	5.55 micromole per liter (μmol/L) Standard Deviation 15.475
Change From Baseline in Creatinine Change at Quarterly Visit 8 (Month 24)	6.11 micromole per liter (μmol/L) Standard Deviation 18.426
Change From Baseline in Creatinine Change at Quarterly Visit 9 (Month 27)	4.93 micromole per liter (μmol/L) Standard Deviation 12.605
Change From Baseline in Creatinine Change at Quarterly Visit 10 (Month 30)	7.37 micromole per liter (μmol/L) Standard Deviation 11.367

SECONDARY outcome

Timeframe: Up to Month 30

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

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.

Outcome measures

Measure	Alphanate n=50 Participants 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.
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 Human Immunodeficiency Virus Type 1 and 2	5 Participants
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 Hepatitis A Virus	21 Participants
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 Hepatitis B Virus (HBsAg)	0 Participants
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 Hepatitis B Virus (HBsAb)	6 Participants
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 Hepatitis C Virus	3 Participants
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 Parvovirus B19	6 Participants

Adverse Events

Alphanate

Serious events: 4 serious events

Other events: 22 other events

Deaths: 0 deaths

Serious adverse events

Measure	Alphanate n=50 participants at risk 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.
Gastrointestinal disorders Gastrointestinal Haemorrhage	2.0% 1/50 • Up to Month 30 Safety population included all participants who received at least one infusion of study medication.
General disorders Device Malfunction	2.0% 1/50 • Up to Month 30 Safety population included all participants who received at least one infusion of study medication.
Injury, poisoning and procedural complications Post Procedural Discharge	2.0% 1/50 • Up to Month 30 Safety population included all participants who received at least one infusion of study medication.
Musculoskeletal and connective tissue disorders Joint Swelling	2.0% 1/50 • Up to Month 30 Safety population included all participants who received at least one infusion of study medication.
Renal and urinary disorders Haematuria	2.0% 1/50 • Up to Month 30 Safety population included all participants who received at least one infusion of study medication.

Other adverse events

Measure	Alphanate n=50 participants at risk 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.
Infections and infestations Upper Respiratory Tract Infection	10.0% 5/50 • Up to Month 30 Safety population included all participants who received at least one infusion of study medication.
Infections and infestations Pharyngitis	6.0% 3/50 • Up to Month 30 Safety population included all participants who received at least one infusion of study medication.
Respiratory, thoracic and mediastinal disorders Cough	16.0% 8/50 • Up to Month 30 Safety population included all participants who received at least one infusion of study medication.
Respiratory, thoracic and mediastinal disorders Oropharyngeal Pain	10.0% 5/50 • Up to Month 30 Safety population included all participants who received at least one infusion of study medication.
Respiratory, thoracic and mediastinal disorders Nasal Congestion	8.0% 4/50 • Up to Month 30 Safety population included all participants who received at least one infusion of study medication.
Injury, poisoning and procedural complications Contusion	6.0% 3/50 • Up to Month 30 Safety population included all participants who received at least one infusion of study medication.
Injury, poisoning and procedural complications Joint Injury	6.0% 3/50 • Up to Month 30 Safety population included all participants who received at least one infusion of study medication.
Injury, poisoning and procedural complications Ligament Sprain	6.0% 3/50 • Up to Month 30 Safety population included all participants who received at least one infusion of study medication.
Injury, poisoning and procedural complications Limb Injury	6.0% 3/50 • Up to Month 30 Safety population included all participants who received at least one infusion of study medication.
Injury, poisoning and procedural complications Skin Abrasion	6.0% 3/50 • Up to Month 30 Safety population included all participants who received at least one infusion of study medication.
Musculoskeletal and connective tissue disorders Arthralgia	8.0% 4/50 • Up to Month 30 Safety population included all participants who received at least one infusion of study medication.
Musculoskeletal and connective tissue disorders Back Pain	6.0% 3/50 • Up to Month 30 Safety population included all participants who received at least one infusion of study medication.
General disorders Pain	8.0% 4/50 • Up to Month 30 Safety population included all participants who received at least one infusion of study medication.
General disorders Pyrexia	8.0% 4/50 • Up to Month 30 Safety population included all participants who received at least one infusion of study medication.
Skin and subcutaneous tissue disorders Acne	6.0% 3/50 • Up to Month 30 Safety population included all participants who received at least one infusion of study medication.
Vascular disorders Haemorrhage	6.0% 3/50 • Up to Month 30 Safety population included all participants who received at least one infusion of study medication.
Nervous system disorders Headche	8.0% 4/50 • Up to Month 30 Safety population included all participants who received at least one infusion of study medication.

Additional Information

Rhonda Griffin

Grifols

Phone: 919-316-6693

Email: rhonda.griffin@grifols.com

Results disclosure agreements

• Principal investigator is a sponsor employee Site may publish results from the Study, after providing Sponsor thirty days' notice prior to submitting a manuscript or other materials related to the Study to any outside party. At Sponsors' request, Site will remove any Confidential Information (other than Study results), and Site will upon Sponsors' request, delay publication or presentation for a period of up to one hundred twenty days to allow Sponsor to protect its interests in any Sponsor Inventions.
• Publication restrictions are in place

Restriction type: OTHER