Phase 1
Completed N=19
Pharmacokinetics of rFVIIIFc at Two Vial Strengths
Source: ClinicalTrials.gov NCT02083965 ↗Enrolled (actual)
19
Serious AEs
10.5%
Results posted
Aug 2016
Primary outcomePrimary: Area Under the Concentration-time Curve From Time Zero to Infinity (AUCinf) as Measured by Activated Partial Thromboplastin Time (aPTT) Clotting Assay — 2888.9; 2646.3 IU*h/dL
Summary
The primary objective of the study is to characterize the pharmacokinetics (PK) of rFVIIIFc administered at vial strengths of 1000 and 3000 IU in subjects with severe hemophilia A. The secondary objective of the study is to evaluate the safety of rFVIIIFc beyond the PK assessment for up to 6 months for a continued treatment period.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Area Under the Concentration-time Curve From Time Zero to Infinity (AUCinf) as Measured by Activated Partial Thromboplastin Time (aPTT) Clotting Assay |
2888.9; 2646.3 | — |
| PRIMARY Incremental Recovery (IR, K Value) as Estimated From the FVIII Activity Data Measured by aPTT Clotting Assay |
2.33; 2.412 | — |
| SECONDARY Maximum Activity (Cmax) as Measured by the aPTT Clotting Assay |
122.2; 129.08 | — |
| SECONDARY Half-life (t½) as Measured by aPTT Clotting Assay |
18.28; 17.49 | — |
| SECONDARY Clearance (CL) as Measured by the aPTT Clotting Assay |
1.807; 2.016 | — |
| SECONDARY Volume of Distribution at Steady State (Vss) as Measured by the aPTT Clotting Assay |
47.00; 48.65 | — |
| SECONDARY Mean Residence Time (MRT) as Measured by the aPTT Clotting Assay |
26.01; 24.13 | — |
| SECONDARY Time of Cmax (Tmax) as Measured by aPTT Clotting Assay |
0.66; 0.58 | — |
| SECONDARY Area Under the Curve to the Last Measurable Time Point (AUClast) as Measured by aPTT Clotting Assay |
2792.5; 2562.2 | — |
| SECONDARY Terminal Exponential Rate Constant (Lambda Z) as Measured by aPTT Clotting Assay |
0.03792; 0.03963 | — |
| SECONDARY Percentage of AUCinf From the Last Data Point to Infinity (AUCext) as Measured by aPTT Clotting Assay |
2.561; 2.279 | — |
| SECONDARY Dose Normalized Area Under the Curve (DNAUC) as Measured by aPTT Clotting Assay |
55.35; 49.6 | — |
| SECONDARY Terminal Exponential Volume of Distribution (Vz) as Measured by aPTT |
47.65; 50.87 | — |
| SECONDARY AUCinf as Estimated From the FVIII Activity Data as Measured by Two-Stage Chromogenic Clotting Assay |
2649.0; 2628.0 | — |
| SECONDARY IR, K Value as Measured by Two-Stage Chromogenic Clotting Assay |
2.535; 2.287 | — |
| SECONDARY Cmax as Measured by Two-Stage Chromogenic Clotting Assay |
132.61; 122.29 | — |
| SECONDARY t½ as Measured by Two-Stage Chromogenic Clotting Assay |
18.58; 19.10 | — |
| SECONDARY CL as Measured by Two-Stage Chromogenic Clotting Assay |
1.962; 2.006 | — |
| SECONDARY Vss as Measured by Two-Stage Chromogenic Clotting Assay |
47.41; 51.27 | — |
| SECONDARY MRT as Measured by Two-Stage Chromogenic Clotting Assay |
24.17; 25.56 | — |
| SECONDARY Tmax as Measured by Two-Stage Chromogenic Clotting Assay |
0.61; 0.61 | — |
| SECONDARY AUClast as Measured by Two-Stage Chromogenic Clotting Assay |
2555.4; 2520.5 | — |
| SECONDARY Lambda Z as Measured by Two-Stage Chromogenic Clotting Assay |
0.03730; 0.03629 | — |
| SECONDARY AUCext as Measured by Two-Stage Chromogenic Clotting Assay |
2.923; 2.965 | — |
| SECONDARY DNAUC as Measured by Two-Stage Chromogenic Clotting Assay |
50.97; 49.85 | — |
| SECONDARY Vz as Measured by Two-Stage Chromogenic Clotting Assay |
52.59; 55.28 | — |
| SECONDARY Development of Inhibitor as Measured by the Nijmegen-Modified Bethesda Assay |
— | — |
Eligibility Criteria
Key Inclusion Criteria
- Have severe hemophilia A
- Previously treated subject, defined as having at least 150 documented prior exposure days to any recombinant and/or plasma-derived FVIII and/or cryoprecipitate products (other than any use of rFVIIIFc- study drug or commercial product) at Day 1. Fresh frozen plasma treatment must not be considered in the count for documented exposure days.
- No history of a positive inhibitor test or clinical signs of decreased response to FVIII administrations. Family history of inhibitors will not exclude subjects.
- No measurable inhibitor activity using the Nijmegen-modified Bethesda assay at Screening.
- Platelet count ≥100,000 platelets/μL at screening
- CD4 lymphocytes >200 mm3 if known as HIV antibody positive at screening.
- Viral load of <400 copies/mL if known HIV antibody positive at screening.
Key Exclusion Criteria
- Subject is at high risk of bleeding during the 5-day period between the first and second injections for PK analyses, as per Investigator discretion.
- Previous treatment with rFVIIIFc as study drug or commercial product.
- Other coagulation disorder(s) in addition to hemophilia A.
- History of hypersensitivity or anaphylaxis associated with any FVIII or IV immunoglobulin administration.
- Currently taking (or likely to require during the study) acetylsalicylic acid (ASA), except for low-dose ASA as prophylaxis (other nonsteroidal anti-inflammatory drugs are permitted).
- Concurrent systemic treatment with immunosuppressive drugs within 12 weeks prior to Day 1. Exceptions to this include: ribavirin for treatment of hepatitis C virus (HCV), and/or systemic steroids (a total of 2 courses of pulse treatments lasting no more than 7 days at a dose of ≤1 mg/kg within 12 weeks prior to Day 1) and/or inhaled steroids.
NOTE: Other protocol-defined inclusion/exclusion Criteria May Apply
Data sourced from ClinicalTrials.gov (NCT02083965). 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.