Phase 3
N=165
Study to Evaluate the Safety, Pharmacokinetics and Efficacy of Recombinant Factor VIII Fc Fusion Protein (rFVIIIFc) in Previously Treated Subjects With Severe Hemophilia A
Severe Hemophilia A
Bottom Line
View on ClinicalTrials.gov: NCT01181128 ↗Enrolled (actual)
165
Serious AEs
7.3%
Results posted
Aug 2014
Primary outcome: Primary: Incidence Rate of FVIII Inhibitor Development — 0; 0; 0; 0 percentage of participants
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 3
- Interventions
- Factor VIII (rFVIIIFc) (Drug); Advate® (Drug)
- Age
- Pediatric, Adult, Older Adult · 12+ yrs
- Sex
- Male
- Sponsor
- Bioverativ Therapeutics Inc.
- Primary completion
- Aug 2012
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Incidence Rate of FVIII Inhibitor Development |
0; 0; 0; 0; 0; 0 | — |
| PRIMARY Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) |
3; 80; 18; 10; 4; 0 | — |
| PRIMARY Number of Participants With Potentially Clinically Significant Abnormal Laboratory Values From Baseline |
2; 0; 2; 1; 0; 0 | — |
| PRIMARY Number of Participants With Clinically Relevant Abnormalities in Vital Signs or Relevant Changes From Baseline in Vital Signs |
1; 0; 0; 11; 2; 0 | — |
| PRIMARY Annualized Bleeding Rate |
1.60; 3.59; 33.57 | — |
| PRIMARY Comparison of Annualized Bleeding Rates: Arm 1 Versus Arm 3 |
2.91; 37.25 | <0.001 sig |
| PRIMARY Area Under the Curve (AUC) Per Dose (One-stage Clotting Assay) |
51.24; 32.88 | — |
| PRIMARY Elimination Half Life (t1/2; One-stage Clotting Assay) |
18.97; 12.43 | — |
| PRIMARY Clearance (CL; One-stage Clotting Assay) |
1.952; 3.041 | — |
| PRIMARY Mean Residence Time (MRT; One-stage Clotting Assay) |
25.15; 16.84 | — |
| PRIMARY Incremental Recovery (One-stage Clotting Assay) |
2.2395; 2.3516 | — |
| SECONDARY Comparison of Annualized Bleeding Rates: Arm 2 Versus Arm 3 |
8.92; 37.25 | <0.001 sig |
| SECONDARY Annualized rFVIIIFc Consumption Per Participant |
4631.98; 4003.69; 1304.36; 4868.35; 3882.89; 1225.80 | — |
| SECONDARY Participant Assessment of Response to Injections to Treat a Bleeding Episode |
79.7; 64.0; 80.2; 33.7; 18.0; 30.8 | — |
| SECONDARY Investigator's Assessment of Participants' Bleeding Response to rFVIIIFc Injection |
— | — |
| SECONDARY Annualized Bleeding Rate by Location of Bleed (Joint, Muscle, Internal, Skin/Mucosa) |
0.00; 1.93; 22.76; 0.00; 0.00; 5.57 | — |
| SECONDARY Annualized Joint Bleeding Rate (Spontaneous and Traumatic) |
0.00; 0.00; 18.59; 0.00; 0.00; 3.93 | — |
| SECONDARY Number of Days From Last Treatment Injection to a New Bleeding Episode |
19.83; 8.00; 6.55; 42.90; 40.71; 10.12 | — |
| SECONDARY Number of Injections Required for Resolution of a Bleeding Episode |
1.0; 1.0; 1.0; 1.00; 1.00; 1.03 | — |
| 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 |
29.69; 28.23; 27.35; 40.98; 32.12; 27.78 | — |
| SECONDARY Volume at Steady State (Vss; One-stage Clotting Assay) |
49.1; 51.2 | — |
| SECONDARY Volume at Steady State (Vss; Two-stage Chromogenic Assay) |
52.6; 56.8 | — |
| SECONDARY Time to 1% and 3% FVIII Activity (One-stage Clotting Assay) |
3.298; 2.478; 4.918; 3.707 | — |
| SECONDARY Time to 1% and 3% FVIII Activity (Two-stage Chromogenic Assay) |
3.220; 2.306; 5.010; 3.612 | — |
| SECONDARY Time at Maximum Activity (Tmax; One-stage Clotting Assay) |
0.49; 0.48 | — |
| SECONDARY Time at Maximum Activity (Tmax; Two-stage Chromogenic Assay) |
0.55; 0.46 | — |
| SECONDARY Area Under the Curve (AUC) Per Dose (Two-stage Chromogenic Assay) |
47.45; 28.05 | — |
| SECONDARY Elimination Half Life (t1/2; Two-stage Chromogenic Assay) |
20.89; 13.67 | — |
| SECONDARY Clearance (CL; Two-stage Chromogenic Assay) |
2.108; 3.566 | — |
| SECONDARY Mean Residence Time (MRT; Two-stage Chromogenic Assay) |
24.96; 15.94 | — |
| SECONDARY Incremental Recovery (Two-stage Chromogenic Assay) |
2.4912; 2.5589 | — |
| SECONDARY Hemophilia-Specific Quality of Life Index for Adults (Haem-A-QoL) Questionnaire: Change From Baseline to Week 14 |
-2.18; -1.48; -4.73; -2.09; -5.00; -12.50 | — |
| SECONDARY Hemophilia-Specific Quality of Life Index for Adults (Haem-A-QoL) Questionnaire: Change From Baseline to Week 28 |
-1.03; -4.31; -5.81; -0.56; 0.00; -25.00 | — |
| SECONDARY Hemophilia-Specific Quality of Life Index for Children (Haemo-QoL) Questionnaire: Change From Baseline to Week 14 and Week 28 in Haemo-QoL III Total Score |
11.20; 26.30; -3.25; -5.01; -3.73; NA | — |
| SECONDARY Investigators'/Surgeons' Assessment of Participants' Response to rFVIIIFc for Major Surgery |
9; 8; 1; 0; 0 | — |
| SECONDARY Number of Injections Required to Maintain Hemostasis During Major Surgery |
1.0 | — |
| SECONDARY Dose Per Injection and Total Dose Required to Maintain Hemostasis During Major Surgery |
51.4; 51.4 | — |
| SECONDARY Estimated Total Blood Loss During Major Surgery |
15.0 | — |
| SECONDARY Number of Transfusions Required Per Surgery |
8; 0; 1; 0; 0 | — |
Summary
The primary objectives of this study are: to evaluate the safety and tolerability of rFVIIIFc administered as a prophylaxis (Arm 1), weekly (Arm 2), on-demand (Arm 3), and surgical treatment regimen; to evaluate the efficacy of the rFVIIIFc tailored prophylaxis regimen (Arm 1); to evaluate the efficacy of rFVIIIFc administered as an on-demand (Arm 3) and surgical treatment regimen. The secondary objectives of this study are: to characterize the PK profile of rFVIIIFc and compare the PK of rFVIIIFc with the currently marketed product, Advate®; to characterize the range of dose and schedules required to adequately prevent bleeding in a prophylaxis regimen, maintain hemostasis in a surgical setting, or to treat bleeding episodes in an on-demand, weekly treatment, or prophylaxis setting.
Eligibility Criteria
Inclusion Criteria
- Male, ≥12 years of age with weight at least 40 kg
- Diagnosed with severe hemophilia A, defined as <1 IU/dL (<1%) endogenous Factor VIII)
- History of at least 150 documented prior exposure days to any Factor VIII product
- Platelet count ≥100,000 cells/μL
Exclusion Criteria
- History of Factor VIII inhibitors
- Kidney and liver dysfunction
- Diagnosed with other coagulation disorder(s) in addition to hemophilia A
- Prior history of hypersensitivity or anaphylaxis associated with any FVIII or IV immunoglobulin administration
Data sourced from ClinicalTrials.gov (NCT01181128). 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.