Phase 3
Completed N=24
Pharmacokinetics and Safety of rFVIIIFc Manufactured at 15,000 L (15K) Scale
Source: ClinicalTrials.gov NCT02502149 ↗Enrolled (actual)
24
Serious AEs
0.0%
Results posted
Apr 2018
Primary outcomePrimary: Area Under the Concentration-time Curve From Time Zero to Infinity (AUCinf) as Measured by One-stage Activated Partial Thromboplastin Time (aPTT) Clotting Assay for Pharmacokinetic Assessment 1 (PK1) and Pharmacokinetic Assessment 2 (PK2) — 2255.6; 2425.8 International unit*hour per deciliter
◆ Published Evidence
No publication linked
No peer-reviewed publication reporting this trial's results has been linked yet. This can indicate results are unpublished — a known publication-bias signal. We re-check periodically.
Summary
The primary objective of the study is to compare the pharmacokinetic (PK) of recombinant coagulation factor VIII Fc fusion protein (rFVIIIFc) manufactured at the current scale of 2000 L (2K) to the PK of rFVIIIFc manufactured at the 15,000 L (15K) scale in previously treated participants with severe hemophilia A. The secondary objectives are: to characterize the PK of rFVIIIFc manufactured at the 15K scale at the 15K baseline and after 13 weeks of treatment; to characterize the PK of rFVIIIFc manufactured at the 15K scale at 1000 IU/vial and 6000 IU/vial strengths; and to evaluate the safety of rFVIIIFc manufactured at the 15K scale.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Area Under the Concentration-time Curve From Time Zero to Infinity (AUCinf) as Measured by One-stage Activated Partial Thromboplastin Time (aPTT) Clotting Assay for Pharmacokinetic Assessment 1 (PK1) and Pharmacokinetic Assessment 2 (PK2) |
2255.6; 2425.8 | — |
| PRIMARY Incremental Recovery (IR) as Measured by One-stage aPTT Clotting Assay for PK1 and PK2 |
2.684; 2.700 | — |
| SECONDARY Maximum Activity (Cmax) of rFVIIIFc as Measured by One-stage aPTT Clotting Assay for PK1 and PK2 |
133.20; 134.67 | — |
| SECONDARY Half-life (t½) of rFVIIIFc as Measured by One-stage aPTT Clotting Assay for PK1 and PK2 |
14.229; 14.771 | — |
| SECONDARY Clearance (CL) of rFVIIIFc as Measured by One-stage aPTT Clotting Assay for PK1 and PK2 |
2.1847; 2.0420 | — |
| SECONDARY Volume of Distribution at Steady State (Vss) of rFVIIIFc as Measured by One-stage aPTT Clotting Assay for PK1 and PK2 |
43.80; 43.01 | — |
| SECONDARY Mean Residence Time (MRT) of rFVIIIFc as Measured by One-stage aPTT Clotting Assay for PK1 and PK2 |
20.048; 21.063 | — |
| SECONDARY Area Under the Concentration-time Curve From Time Zero to Infinity (AUCinf) as Measured by One-stage aPTT Clotting Assay for PK2 and PK3 |
2448.6; 2697.8 | — |
| SECONDARY Incremental Recovery (IR) as Measured by One-stage aPTT Clotting Assay for PK2 and PK3 |
2.693; 2.804 | — |
| SECONDARY Maximum Activity (Cmax) of rFVIIIFc as Measured by One-stage aPTT Clotting Assay for PK2 and PK3 |
134.67; 140.38 | — |
| SECONDARY Half-life (t½) of rFVIIIFc as Measured by One-stage aPTT Clotting Assay for PK2 and PK3 |
14.771; 15.493 | — |
| SECONDARY Clearance (CL) of rFVIIIFc as Measured by One-stage aPTT Clotting Assay for PK2 and PK3 |
2.0420; 1.8556 | — |
| SECONDARY Volume of Distribution at Steady State (Vss) of rFVIIIFc as Measured by One-stage aPTT Clotting Assay for PK2 and PK3 |
43.01; 40.19 | — |
| SECONDARY Mean Residence Time (MRT) of rFVIIIFc as Measured by One-stage aPTT Clotting Assay for PK2 and PK3 |
21.063; 21.657 | — |
| SECONDARY Area Under the Concentration-time Curve From Time Zero to Infinity (AUCinf) as Measured by One-stage aPTT Clotting Assay for PK2 at Different Vial Strengths (1000 and 6000 IU/Vial) |
2356.8; 2535.8 | — |
| SECONDARY Incremental Recovery (IR) of rFVIIIFc as Measured by One-stage aPTT Clotting Assay for PK2 at Different Vial Strengths (1000 and 6000 IU/Vial) |
2.614; 2.768 | — |
| SECONDARY Maximum Activity (Cmax) of rFVIIIFc as Measured by One-stage aPTT Clotting Assay for PK2 at Different Vial Strengths (1000 and 6000 IU/Vial) |
130.73; 138.40 | — |
| SECONDARY Half-life (t½) of rFVIIIFc as Measured by One-stage aPTT Clotting Assay for PK2 at Different Vial Strengths (1000 and 6000 IU/Vial) |
14.118; 15.395 | — |
| SECONDARY Clearance (CL) of rFVIIIFc as Measured by One-stage aPTT Clotting Assay for PK2 at Different Vial Strengths (1000 and 6000 IU/Vial) |
2.1215; 1.9718 | — |
| SECONDARY Volume of Distribution at Steady State (Vss) of rFVIIIFc as Measured by One-stage aPTT Clotting Assay for PK2 at Different Vial Strengths (1000 and 6000 IU/Vial) |
42.61; 43.38 | — |
| SECONDARY Mean Residence Time (MRT) of rFVIIIFc as Measured by One-stage aPTT Clotting Assay for PK2 at Different Vial Strengths (1000 and 6000 IU/Vial) |
20.087; 22.000 | — |
| SECONDARY Area Under the Concentration-time Curve From Time Zero to Infinity (AUCinf) as Measured by One-stage aPTT Clotting Assay for PK3 at Different Vial Strengths (1000 and 6000 IU/Vial) |
2634.5; 2746.3 | — |
| SECONDARY Incremental Recovery (IR) of rFVIIIFc as Measured by One-stage aPTT Clotting Assay for PK3 at Different Vial Strengths (1000 and 6000 IU/Vial) |
2.623; 2.982 | — |
| SECONDARY Maximum Activity (Cmax) of rFVIIIFc as Measured by One-stage aPTT Clotting Assay for PK3 at Different Vial Strengths (1000 and 6000 IU/Vial) |
131.15; 149.41 | — |
| SECONDARY Half-life (t½) of rFVIIIFc as Measured by One-stage aPTT Clotting Assay for PK3 at Different Vial Strengths (1000 and 6000 IU/Vial) |
15.599; 15.414 | — |
| SECONDARY Clearance (CL) of rFVIIIFc as Measured by One-stage aPTT Clotting Assay for PK3 at Different Vial Strengths (1000 and 6000 IU/Vial) |
1.8979; 1.8246 | — |
| SECONDARY Volume of Distribution at Steady State (Vss) of rFVIIIFc as Measured by One-stage aPTT Clotting Assay for PK3 at Different Vial Strengths (1000 and 6000 IU/Vial) |
42.12; 38.80 | — |
| SECONDARY Mean Residence Time (MRT) of rFVIIIFc as Measured by One-stage aPTT Clotting Assay for PK3 at Different Vial Strengths (1000 and 6000 IU/Vial) |
22.193; 21.264 | — |
| SECONDARY Area Under the Concentration-time Curve From Time Zero to Infinity (AUCinf) as Measured by the Two-stage Chromogenic Assay for PK1 and PK2 |
2386.4; 2777.6 | — |
| SECONDARY Incremental Recovery (IR) as Measured by the Two-stage Chromogenic Assay for PK1 and PK2 |
2.807; 3.253 | — |
| SECONDARY Maximum Activity (Cmax) of rFVIIIFc as Measured by the Two-stage Chromogenic Assay for PK1 and PK2 |
140.36; 162.73 | — |
| SECONDARY Half-life (t½) of rFVIIIFc as Measured by the Two-stage Chromogenic Assay for PK1 and PK2 |
17.312; 18.146 | — |
| SECONDARY Clearance (CL) of rFVIIIFc as Measured by the Two-stage Chromogenic Assay for PK1 and PK2 |
2.0952; 1.8001 | — |
| SECONDARY Volume of Distribution at Steady State (Vss) of rFVIIIFc as Measured by the Two-stage Chromogenic Assay for PK1 and PK2 |
46.87; 42.02 | — |
| SECONDARY Mean Residence Time (MRT) of rFVIIIFc as Measured by the Two-stage Chromogenic Assay for PK1 and PK2 |
22.370; 23.342 | — |
| SECONDARY Area Under the Concentration-time Curve From Time Zero to Infinity (AUCinf) as Measured by the Two-stage Chromogenic Assay for PK2 and PK3 |
2777.6; 2754.9 | — |
| SECONDARY Incremental Recovery (IR) as Measured by the Two-stage Chromogenic Assay for PK2 and PK3 |
3.253; 2.956 | — |
| SECONDARY Maximum Activity (Cmax) of rFVIIIFc as Measured by the Two-stage Chromogenic Assay for PK2 and PK3 |
162.73; 147.97 | — |
| SECONDARY Half-life (t½) of rFVIIIFc as Measured by the Two-stage Chromogenic Assay for PK2 and PK3 |
18.146; 17.289 | — |
| SECONDARY Clearance (CL) of rFVIIIFc as Measured by the Two-stage Chromogenic Assay for PK2 and PK3 |
1.8001; 1.8173 | — |
| SECONDARY Volume of Distribution at Steady State (Vss) of rFVIIIFc as Measured the Two-stage Chromogenic Assay for PK2 and PK3 |
42.02; 40.59 | — |
| SECONDARY Mean Residence Time (MRT) of rFVIIIFc as Measured by the Two-stage Chromogenic Assay for PK2 and PK3 |
23.342; 22.337 | — |
| SECONDARY Area Under the Concentration-time Curve From Time Zero to Infinity (AUCinf) as Measured by the Two-stage Chromogenic Assay for PK2 at Different Vial Strengths (1000 and 6000 IU/Vial) |
2599.2; 2951.9 | — |
| SECONDARY Incremental Recovery (IR) of rFVIIIFc as Measured by the Two-stage Chromogenic Assay for PK2 at Different Vial Strengths (1000 and 6000 IU/Vial) |
3.225; 3.278 | — |
| SECONDARY Maximum Activity (Cmax) of rFVIIIFc as Measured by the Two-stage Chromogenic Assay for PK2 at Different Vial Strengths (1000 and 6000 IU/Vial) |
161.38; 163.97 | — |
| SECONDARY Half-life (t½) of rFVIIIFc as Measured by the Two-stage Chromogenic Assay for PK2 at Different Vial Strengths (1000 and 6000 IU/Vial) |
16.687; 19.595 | — |
| SECONDARY Clearance (CL) of rFVIIIFc as Measured by the Two-stage Chromogenic Assay for PK2 at Different Vial Strengths (1000 and 6000 IU/Vial) |
1.9236; 1.6938 | — |
| SECONDARY Volume of Distribution at Steady State (Vss) of rFVIIIFc as Measured by the Two-stage Chromogenic Assay for PK2 at Different Vial Strengths (1000 and 6000 IU/Vial) |
41.15; 42.83 | — |
| SECONDARY Mean Residence Time (MRT) of rFVIIIFc as Measured by the Two-stage Chromogenic Assay for PK2 at Different Vial Strengths (1000 and 6000 IU/Vial) |
21.391; 25.287 | — |
| SECONDARY Area Under the Concentration-time Curve From Time Zero to Infinity (AUCinf) as Measured by the Two-stage Chromogenic Assay for PK3 at Different Vial Strengths (1000 and 6000 IU/Vial) |
2646.8; 2829.4 | — |
| SECONDARY Incremental Recovery (IR) of rFVIIIFc as Measured by the Two-stage Chromogenic Assay for PK3 at Different Vial Strengths (1000 and 6000 IU/Vial) |
2.891; 3.016 | — |
| SECONDARY Maximum Activity (Cmax) of rFVIIIFc as Measured by the Two-stage Chromogenic Assay for PK3 at Different Vial Strengths (1000 and 6000 IU/Vial) |
144.58; 151.15 | — |
| SECONDARY Half-life (t½) of rFVIIIFc as Measured by the Two-stage Chromogenic Assay for PK3 at Different Vial Strengths (1000 and 6000 IU/Vial) |
16.945; 17.522 | — |
| SECONDARY Clearance (CL) of rFVIIIFc as Measured by the Two-stage Chromogenic Assay for PK3 at Different Vial Strengths (1000 and 6000 IU/Vial) |
1.8891; 1.7709 | — |
| SECONDARY Volume of Distribution at Steady State (Vss) of rFVIIIFc as Measured by the Two-stage Chromogenic Assay for PK3 at Different Vial Strengths (1000 and 6000 IU/Vial) |
41.78; 39.82 | — |
| SECONDARY Mean Residence Time (MRT) of rFVIIIFc as Measured by the Two-stage Chromogenic Assay for PK3 at Different Vial Strengths (1000 and 6000 IU/Vial) |
22.119; 22.483 | — |
| SECONDARY Development of Inhibitors as Measured by the Nijmegen-modified Bethesda Assay |
— | — |
| SECONDARY Number of Participants With Treatment Emergent Adverse Events (TEAEs) at 15K Manufacturing Scale |
10 | — |
| SECONDARY Number of Participants With Treatment Emergent Serious Adverse Events (TESAEs) at 15K Manufacturing Scale |
— | — |
Eligibility Criteria
Key Inclusion Criteria
- Have severe hemophilia A, defined as =0.6 Bethesda Unit per milliliter [BU/mL] is considered positive) at Screening.
Key Exclusion Criteria
- Current enrollment in any interventional clinical study in which an investigational drug or approved therapy for investigational use is administered within 30 days prior to the Baseline Visit OR prior participation in any of the following Biogen studies: 998HA101 (NCT01027377), 997HA301 (NCT01181128), 8HA02PED (NCT01458106), 997HA307 (NCT02083965), and 8HA01EXT (NCT01454739).
- Previous participation in this study.
- Any concurrent clinically significant major disease that, in the opinion of the Investigator or Biogen, makes the subject unsuitable for participation in the study.
- Other coagulation disorder(s) in addition to hemophilia A.
- History of hypersensitivity or anaphylaxis associated with FVIII or intravenous (IV) immunoglobulin administration.
NOTE: Other protocol-defined inclusion/exclusion criteria may apply.
Data sourced from ClinicalTrials.gov (NCT02502149). 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. Informational only — not medical advice.