Phase 4
N=73
Prophylaxis Study of Recombinant Factor VIII Manufactured Protein-Free (rAHF-PFM) in Patients With Hemophilia A
Hemophilia A
Bottom Line
View on ClinicalTrials.gov: NCT00243386 ↗Enrolled (actual)
73
Serious AEs
9.3%
Results posted
Nov 2012
Primary outcome: Primary: Mean Transformed Annualized Bleed Rate Estimates From Each of the 1-year Prophylaxis Regimens — 1.61; 1.46 (bleeds/year)^(1/2) — p=0.6016
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 4
- Interventions
- Antihemophilic factor, recombinant, manufactured protein-free (Drug)
- Age
- Pediatric, Adult, Older Adult · 7+ yrs
- Sex
- All
- Sponsor
- Baxalta now part of Shire
- Primary completion
- Jun 2010
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Mean Transformed Annualized Bleed Rate Estimates From Each of the 1-year Prophylaxis Regimens |
1.61; 1.46 | 0.6016 |
| PRIMARY Median Annualized Bleed Rate Estimates From Each of the 1 Year Prophylaxis Regimens |
2.01; 1.00 | 0.1467 |
| SECONDARY Mean Difference of Transformed Annualized Bleeding Rate Between On-Demand and Standard Prophylaxis Treatment Regimens |
5.29 | <0.0001 sig |
| SECONDARY Mean Difference of Transformed Annualized Bleeding Rate Between On-Demand and PK-Driven Prophylaxis Treatment Regimens |
5.00 | <0.0001 sig |
| SECONDARY Mean Difference of Transformed Annualized Bleeding Rate Between On-Demand and Any Prophylaxis Treatment Regimens |
5.14 | <0.0001 sig |
| SECONDARY Total Weight-Adjusted Dose of rAHF-PFM Used Per Year for Each Prophylaxis Arm |
5197.8; 5768.2 | 0.4924 |
| SECONDARY Bleeding Episodes Treated With 1 to ≥4 Infusions |
1168; 68; 90; 277; 12; 37 | — |
| SECONDARY Assessment of Hemostasis for Treatment of Bleeding Episodes |
547; 39; 33; 943; 38; 75 | — |
| SECONDARY Total Area Under the Curve (AUC) |
1334.45; 1061.26 | — |
| SECONDARY Area Under the Curve |
1213.98; 966.68 | — |
| SECONDARY Maximum Plasma Concentration (C-max) |
91.12; 74.47 | — |
| SECONDARY Adjusted Incremental Recovery (IR) |
1.81; 1.47 | — |
| SECONDARY Terminal Half-life |
13.91; 14.66 | — |
| SECONDARY Weight-Adjusted Clearance |
3.89; 5.17 | — |
| SECONDARY Mean Residence Time |
17.71; 17.88 | — |
| SECONDARY Volume of Distribution at Steady State |
0.65; 0.84 | — |
| SECONDARY Factor VIII Inhibitor Development |
— | — |
| SECONDARY Number of Participants With AEs Related to Investigational Product (IP) |
4 | — |
| SECONDARY Number of Participants Who Reported ≥1 AE Regardless of Relatedness to Investigational Product (IP) |
44 | — |
| SECONDARY Number of Participants Who Reported ≥1 AE Regardless of Relatedness to IP by Treatment Regimen |
33; 15; 19 | — |
| SECONDARY Number of Participants With SAEs by Preferred MedDRA Term and Treatment Regimen |
1; 0; 0; 0; 1; 0 | — |
| SECONDARY AEs With Onset ≤1 Hour Following the End of an Infusion, Regardless of Relatedness |
39 | — |
| SECONDARY Number of Participants With Severe SAEs and Severe Non-SAEs by Preferred MedDRA Term and Treatment Regimen |
1; 0; 0; 0; 0; 1 | — |
| SECONDARY Baseline Health-related Quality of Life (HRQoL) Scores: PF, RP, BP, GH, VT, SF, RE, MH, PCS, and MCS |
44.56; 42.10; 46.48; 43.87; 51.42; 46.28 | — |
| SECONDARY Health-related Quality of Life (HRQoL) Scores: PF, RP, BP, GH, VT, SF, RE, MH, PCS, and MCS at the End of Treatment Regimens |
46.5; 51.6; 51.6; 51.6; 43.9; 48.6 | — |
| SECONDARY HRQoL Scores Change From On-Demand Treatment Regimen Period Through Prophylaxis Period |
0.00; -2.10; -2.10; 0.00; 0.00; 0.00 | — |
| SECONDARY Bodily Pain HRQoL Scores Change From On-Demand Period Through Prophylaxis Period |
0.00 | 0.0007 sig |
| SECONDARY Physical Component Scores (PCS) HRQoL Scores Change From On-Demand Period Through Prophylaxis Period |
-2.76 | 0.0002 sig |
Summary
The primary purpose of this randomized, two-arm parallel clinical study in 66 previously treated patients with severe or moderately severe hemophilia A is to compare the rate of bleeding episodes for standard prophylaxis (20-40 IU/kg every 48 ± 6 hours; actual dose determined by the investigator) with that of alternate prophylaxis (20-80 IU/kg every 72 + 6 hours; actual dose determined by Baxter utilizing an algorithm and the patient's pharmacokinetic data). The rates of bleeding episodes for the on-demand regimen and the prophylaxis regimens will also be compared for the cross-over portion of the study. Enrolled patients will be treated originally on demand for a period of 6 months and then they will be randomized into one of the prophylaxis arms. Prophylactic treatment will last for a period of 12 months +/- 2 weeks.
Eligibility Criteria
Inclusion Criteria
- The subject has severe or moderately severe hemophilia A as defined by a baseline factor VIII level (greater than) 60
- The subject is human immunodeficiency virus negative (HIV-) or is HIV+ with a CD4 count >= 400 cells/mm³ (CD4 count determined at screening, if necessary)
- The subject has been on a documented on-demand treatment regimen for at least 12 months immediately prior to enrollment
- The subject has a documented history (e.g. in medical charts or dispensing information, or signed investigator statement) of at least 8 joint hemorrhages in the 12 months immediately prior to enrollment
- The subject resides within the coverage area of the mobile compliance device; coverage area will be determined at screening
- The subject or the subject's legally authorized representative has provided written informed consent
Exclusion Criteria
- The subject has a known hypersensitivity to factor VIII concentrates or mouse or hamster proteins
- The subject has a history of factor VIII inhibitors with a titer >= 0.6 BU (by Bethesda or Nijmegen assay) at any time prior to screening
- The subject has a detectable factor VIII inhibitor at screening, with a titer >= 0.4 BU (by Nijmegen Assay) in the central laboratory
- The subject has severe chronic liver disease as evidenced by, but not limited to, any of the following: International Normalized Ratio (INR) > 1.4, hypoalbuminemia, portal vein hypertension including presence of otherwise unexplained splenomegaly and history of esophageal varices.
- The subject has been diagnosed with an inherited or acquired hemostatic defect other than hemophilia A (e.g., qualitative platelet defect or von Willebrand's Disease)
- The subject has been treated during the last sixty (60) days prior to or is being treated at screening/enrollment with an immunomodulating drug.
- The subject has participated in another investigational study within thirty (30) days of enrollment
- The subject has previously participated in a clinical study with rAHF-PFM
- The subject's clinical condition may require a major surgery (defined as moderate to critical risk and perioperative blood loss ≥ 500 mL) during the period of the subject's participation in the study
- The subject is female of childbearing potential with a positive pregnancy test
Data sourced from ClinicalTrials.gov (NCT00243386). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.