Efficacy and Safety Study of a Recombinant Protein-Free Manufactured Factor VIII (rAHF-PFM) in Previously Untreated Hemophilia A Patients

Phase 3

Completed

Conditions: Hemophilia A

Interventions: Biological: Recombinant Antihemophilic Factor Manufactured and Formulated without Added Human or Animal Proteins (rAHF-PFM)

Registration Number: NCT00157157

Lead Sponsor: Baxalta now part of Shire

Brief Summary: The purpose of this study is to evaluate whether Antihemophilic factor, recombinant, manufactured protein-free (rAHF-PFM) is effective and safe in the treatment of hemophilia A patients who have not been treated with factor VIII (FVIII) before.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 66

Inclusion Criteria

The subject has severe or moderately severe hemophilia A as defined by a baseline factor VIII level <= 2% of normal, as documented at screening
The subject is < 6 years of age
The subject's legally authorized representative has provided written informed consent

Exclusion Criteria

The subject has a history of exposure to factor VIII other than rAHF PFM or more than 3 infusions of commercially available rAHF PFM (i.e., ADVATE) within 28 days prior to screening, as determined by the subject's medical history. Any infusion of factor VIII replacement products prior to the 28-day period excludes the subject from participation
The subject has received more than 3 infusions of rAHF PFM (commercially available and/or study product) between screening and prior to the initial recovery infusion
The subject has a detectable inhibitor to factor VIII, as measured in the screening sample by the Nijmegen assay in the central laboratory
The subject has a history of inhibitor to factor VIII at any time prior to screening
The subject has a known hypersensitivity to rAHF PFM
The subject has any 1 of the following laboratory abnormalities at the time of screening:
1. Platelet count < 100,000/mm^3
2. Hemoglobin concentration < 10 g/dL (100 g/L)
3. Serum creatinine > 1.5 times the upper limit of normal (ULN) for age
4. Total bilirubin > 2 times the ULN for age
The subject has an inherited or acquired hemostatic defect other than hemophilia A (e.g., qualitative platelet defect or von Willebrand's disease)
The subject is known to be seropositive for human immunodeficiency virus (HIV), hepatitis C virus (HCV), or hepatitis B virus (HBV), as determined by the subject's medical history
At the time of enrollment, the subject has a clinically significant chronic disease other than hemophilia A
The subject is currently participating in another investigational drug study, or has participated in any clinical study involving an investigational drug within 120 days of the screening visit
The subject (or the subject's legally authorized representative) is identified by the investigator as being unable or unwilling to cooperate with study procedures
The subject has received any blood product, including packed red blood cells (RBC), platelets, plasma, or cryoprecipitate

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Single Arm - All Participants	Recombinant Antihemophilic Factor Manufactured and Formulated without Added Human or Animal Proteins (rAHF-PFM)	All subjects enrolled in the study who meet the eligibility criteria.

Primary Outcome Measures

Name	Time	Method
Factor VIII Inhibitor Development	Assessed during study period which was to be at least 75 exposure days or 3 years (whichever came first)	Percentage of treated participants who developed factor VIII inhibitors

Secondary Outcome Measures

Name	Time	Method
Assessment of Intra-operative Hemostasis	Assessed at the time of discharge from recovery room	Number of surgical procedures managed with rAHF-PFM and with surgeon's assessment of hemostasis based on a 4-point ordinal scale: Excellent: ≤ average predicted blood loss for matched procedures in healthy individuals Good: \> average predicted blood loss, but ≤ maximal predicted blood loss for matched procedures in healthy individuals Fair: \> maximal predicted blood loss for matched procedures in healthy individuals, and hemostasis was achieved None: uncontrolled hemostasis with proper dosing, necessitating a change in treatment regimen
Assessment of Postoperative Hemostasis	Assessed at the time of discharge from hospital or clinic	Number of surgical procedures managed with rAHF-PFM and with investigator's assessment of hemostasis based on a 4-point ordinal scale: Excellent: hemostasis was as good as or better than other licensed factor VIII products for matched procedure Good: hemostasis was probably as good as other licensed factor VIII products for matched procedure Fair: hemostasis was clearly \< optimal for matched procedure, without need to change regimen None: bleeding from inadequate response with proper dosing, necessitating a change in regimen
Development of Antibodies to Heterologous Proteins	Assessed at baseline, throughout the duration of the study, which was to be at least 75 exposure days or 3 years (whichever came first), and at the termination visit.	Percentage of treated participants who developed antibodies to heterologous proteins (ie, Chinese Hamster Ovary Cell Protein, Murine IgG, or Recombinant Human VWF)
Assessment of Blood Loss During Surgical Procedures	Predicted volumes preoperatively estimated and actual volumes intraoperatively recorded	Percentage of actual intraoperative blood loss compared to preoperatively predicted average and maximal blood loss in hemostatically normal matched individuals (from institutional blood bank records)
Bleeding Episodes Treated With 1 to ≥4 Infusions	Reported during study period which was to be at least 75 exposure days or 3 years (whichever came first)	The number of bleeding episodes treated with 1, 2, 3, or ≥4 infusions of rAHF-PFM to achieve adequate hemostasis
Assessment of Hemostasis for Treatment of Bleeding Episodes	Reported during study period which was to be at least 75 exposure days or 3 years (whichever came first)	Number of rAHF-PFM-treated bleeding episodes with treater assessment of hemostasis (4-point ordinal scale): Excellent: Full pain relief \& bleeding cessation within \~8 hrs of 1 infusion. Additional infusions may have been given to maintain hemostasis; Good: Definite pain relief and/or improvement in bleeding within \~8 hrs after infusion. Possibly requires \>1 infusion for complete resolution; Fair: Probable or slight relief of pain \& slight improvement in bleeding within \~8 hrs after infusion. Requires \>1 infusion for complete resolution; or None: No improvement or condition worsens.
Annualized Rate of Bleeding Episodes	Reported during study period which was to be at least 75 exposure days or 3 years (whichever came first)	Number of bleeding episodes per subject annualized over 1 year for all etiologies
Weekly rAHF-PFM Utilization	Reported during study period which was to be at least 75 exposure days or 3 years (whichever came first)	Weight-Adjusted Weekly Dose for Prophylaxis, On-Demand Treatment, and Perioperative Management. rAHF-PFM dose determined by the investigator (ie: standard regimen \[25-50 IU/kg body weight, 3-4 times per week\]; modified prophylactic regimen \[dose and frequency selected by investigator\] or on-demand treatment \[dose selected by investigator\]). Dosing to treat BEs was at investigator's discretion and in accordance with institution's standard of care. rAHF-PFM was administered I.V. via bolus infusion, except for perioperative management when it was given either by continuous or bolus infusion.
In Vivo Incremental Recovery	30 minutes pre-infusion to 30 minutes post-infusion	Change in factor VIII concentration from pre- to post-infusion at initial and termination study visits.
Adverse Events Deemed Related to Treatment	Reported during the study period which was to be at least 75 exposure days or 3 years (whichever came first)	Percentage of participants who reported AEs deemed related to treatment with rAHF-PFM