Phase 3
N=123
Study of Recombinant Factor IX Fc Fusion Protein (rFIXFc) in Participants With Hemophilia B
Severe Hemophilia B
Bottom Line
View on ClinicalTrials.gov: NCT01027364 ↗Enrolled (actual)
123
Serious AEs
10.9%
Results posted
Sep 2014
Primary outcome: Primary: Number of Participants With Potentially Clinically Significant Laboratory Abnormalities — 2; 0; 2; 0 participants
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 3
- Interventions
- Factor IX (rFIXFc) (Drug); rFIX (Drug)
- Age
- Pediatric, Adult, Older Adult · 12+ yrs
- Sex
- Male
- Sponsor
- Bioverativ Therapeutics Inc.
- Primary completion
- Jul 2012
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Number of Participants With Potentially Clinically Significant Laboratory Abnormalities |
2; 0; 2; 0; 0; 0 | — |
| PRIMARY Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) |
2; 45; 23; 20; 10; 0 | — |
| PRIMARY Number of Participants With Non-serious Treatment-emergent Adverse Events (TEAEs) During the Surgical / Rehabilitation Period |
2; 1; 1; 1; 1; 1 | — |
| PRIMARY Number of Participants With Treatment-emergent Serious Adverse Events (TESAEs) During the Surgical / Rehabilitation Period |
1; 1; 1; 1; 1 | — |
| PRIMARY Incidence Rate of FIX Inhibitor Development |
0; 0; 0; 0; 0; 0 | — |
| PRIMARY Annualized Bleeding Rate |
2.95; 1.38; 17.69 | — |
| PRIMARY Comparison of Annualized Bleeding Rates |
3.12; 2.40; 18.67 | <0.001 sig |
| SECONDARY Participant Assessment of Response to Injections to Treat a Bleeding Episode |
78.8; 74.6; 87.1; 35.3; 31.7; 37.3 | — |
| SECONDARY Physicians' Global Assessments of Participants' Response to Treatment With rFIXFc |
74.5; 73.2; 58.3; 24.3; 26.0; 39.6 | — |
| SECONDARY Annualized rFIXFc Consumption Per Participant |
2686.94; 3371.92; 936.70; 2467.32; 3497.78; 957.73 | — |
| SECONDARY Average Weekly Dose For the Fixed Weekly Interval Prophylaxis Arm |
46.26; 43.10 | — |
| SECONDARY Average Dosing Interval For the Individualized Interval Prophylaxis Arm |
12.53; 14.00 | — |
| SECONDARY Annualized Bleeding Rate by Type of Bleed (Spontaneous and Traumatic) |
1.04; 0.88; 11.78; 0.99; 0.00; 2.21 | — |
| SECONDARY Annualized Bleeding Rate by Location of Bleed (Joint, Muscle, Internal, Skin/Mucosa) |
1.11; 0.36; 13.58; 0.00; 0.00; 3.96 | — |
| SECONDARY Number of Days From Last Injection to Treat a New Bleeding Episode |
40.78; 39.48; 13.42; 59.52; 76.13; 19.67 | — |
| SECONDARY Number of Injections Required for Resolution of a Bleeding Episode |
1.0; 1.0; 1.0; 1.00; 1.09; 1.04 | — |
| SECONDARY Number of Injections Required for Resolution of a Bleeding Episode by Location of Bleed |
1.0; 1.0; 1.0; 1.0; 1.0; 1.0 | — |
| SECONDARY Total Dose Per Injection Required for Resolution of a Bleeding Episode by Location of Bleed |
50.14; 45.29; 46.73; 55.56; 67.17; 46.57 | — |
| SECONDARY Hemophilia-Specific Quality of Life Index for Adults (Haem-A-QoL) Questionnaire: Change From Baseline to Week 26 |
-6.82; -6.25; -10.00; -15.00; 0.00; 0.00 | — |
| SECONDARY Haem-A-QoL Questionnaire for Adults: Change From Baseline to Week 52 |
-4.35; -6.06; -10.00; -15.00; 0.00; 0.00 | — |
| SECONDARY Hemophilia-Specific Quality of Life Index for Children (Haemo-QoL) Questionnaire: Change From Baseline to Week 26 and Week 52 |
— | — |
| SECONDARY Investigators'/Surgeons' Assessment of Participants' Response to rFIXFc for Major Surgery |
14; 13; 1; 0; 0 | — |
| SECONDARY Number of Injections Required to Maintain Hemostasis During Major Surgery |
1.00 | — |
| SECONDARY Dose Per Injection and Total Dose Required to Maintain Hemostasis During Major Surgery |
90.91; 102.59 | — |
| SECONDARY Estimated Total Blood Loss During Major Surgery |
65.50 | — |
| SECONDARY Number of Transfusions Required Per Surgery |
12; 0; 1; 0; 1 | — |
| SECONDARY Maximum Concentration (Cmax) |
40.81; 43.08 | — |
| SECONDARY Area Under the Curve (AUC) Per Dose |
31.32; 15.77 | — |
| SECONDARY Half Life (t1/2) Alpha and t1/2 Beta |
5.0279; 2.4113; 82.12; 33.77 | — |
| SECONDARY Clearance (CL) |
3.193; 6.340 | — |
| SECONDARY Mean Residence Time (MRT) |
98.60; 41.19 | — |
| SECONDARY Volume in Steady State (Vss) |
314.8; 261.1 | — |
| SECONDARY Incremental Recovery |
0.9211; 0.9451 | — |
| SECONDARY Time to 1% and 3% FIX Activity |
11.224; 5.087; 5.767; 2.832 | — |
| SECONDARY Number of Participants With Clinically Relevant Abnormalities or Relevant Changes From Baseline in Vital Signs |
0; 0; 0; 1; 2; 0 | — |
| SECONDARY Coagulation Parameter: Change From Pre-dose Values in Prothrombin Split Fragments 1+ 2 (F 1+2) |
134.1; 130.0; 131.6; 176.7; 73.4; 8.6 | — |
| SECONDARY Coagulation Parameter: Change From Pre-dose Values in Thrombin-antithrombin (TAT) Complex |
2.87; 2.87; 3.11; 4.28; 6.67; 1.05 | — |
| SECONDARY Coagulation Parameter: Change From Pre-dose Values in D-dimer |
153.0; 176.2; 120.5; 134.7; 35.9; 89.6 | — |
Summary
The primary objectives of the study were: to evaluate the safety and tolerability of rFIXFc; to evaluate the efficacy of rFIXFc in all treatment arms; to evaluate the effectiveness of prophylaxis over on-demand (episodic) therapy by comparing the annualized number of bleeding episodes between participants receiving rFIXFc on each prevention (prophylaxis) regimen and participants receiving rFIXFc on an episodic regimen. The secondary objectives of the study were: to evaluate and assess the pharmacokinetic (PK) parameter estimates of rFIXFc and rFIX (BeneFIX®) at baseline in the Sequential PK subgroup as well as rFIXFc at Week 26 (±1 week); to evaluate participants' response to treatment; to evaluate rFIXFc consumption.
Eligibility Criteria
Inclusion Criteria
- Male and 12 years of age and older and weigh at least 40 kg
- Diagnosed with hemophilia B (baseline Factor IX level less than or equal to 2%)
- History of at least 100 exposure days to any Factor IX product
- Platelet count ≥100,000 cells/μL
Exclusion Criteria
- History of Factor IX inhibitors
- Kidney or liver dysfunction
- Diagnosed with another coagulation defect other than hemophilia B
- Prior history of anaphylaxis associated with any Factor IX or intravenous (IV) immunoglobulin administration
Data sourced from ClinicalTrials.gov (NCT01027364). 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.