Phase 2
N=51
Haemophilia Patients With Inhibitors Being Treated for Acute Joint Bleeds
Congenital Bleeding Disorder · Haemophilia A · Haemophilia B
Bottom Line
View on ClinicalTrials.gov: NCT00486278 ↗Enrolled (actual)
51
Serious AEs
11.5%
Results posted
Dec 2014
Primary outcome: Primary: Number of Adverse Events (AEs) — 10; 8; 5; 5 events
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- eptacog alfa (activated) (Drug); vatreptacog alfa (activated) (Drug)
- Age
- Pediatric, Adult, Older Adult · 12+ yrs
- Sex
- Male
- Sponsor
- Novo Nordisk A/S
- Primary completion
- Jun 2010
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Number of Adverse Events (AEs) |
10; 8; 5; 5; 0; 11 | — |
| SECONDARY Activated Recombinant Human Factor VII Analogue Activity in the Blood |
0.1; 0.1; 0; 0.1; 5.3; 12.8 | — |
| SECONDARY Prothrombin Time (PT) |
80.1; 77.6; 79.1; 85.9; 85.5; 88.3 | — |
| SECONDARY F1 + 2 (Prothrombin Fragments 1+2) |
289.8; 131.8; 139.1; 121.2; 125.4; 169.3 | — |
| SECONDARY Activated Partial Thromboplastin Time (aPTT) |
120.6; 126.0; 122.8; 119.2; 117.4; 113.8 | — |
| SECONDARY Cessation of Bleeding: Number of Doses Needed to Control Bleeding |
3; 3; 2; 5; 4; 6 | — |
| SECONDARY Number of Subjects With Need for Additional Haemostatic Agents |
4; 1; 1; 1; 1; 1 | — |
| SECONDARY Pharmacokinetic Parameters Based on FVIIa Activity: AUC 0-t (Area Under the Plasma FVIIa Activity-time Curve From Time Zero to the Time (t) ) |
34.24; 66.85; 136.19; 74.35 | — |
| SECONDARY Pharmacokinetic Parameters Based on FVIIa Activity: AUC(0-inf) (Area Under the Plasma FVIIa Activity-time Curve From Time Zero to Infinity) |
35.76; 71.23; 139.63; 101.38 | — |
| SECONDARY Pharmacokinetic Parameters Based on FVIIa Activity: MRT (Mean Residence Time) |
0.68; 0.88; 0.56; 2.23 | — |
| SECONDARY Pharmacokinetic Parameters Based on FVIIa Activity: t½ (Terminal Half-life) |
0.92; 1.28; 0.71; 1.66 | — |
| SECONDARY Pharmacokinetic Parameters Based on FVIIa Activity: CL (Total Clearance) |
9365.8; 11247; 10409; 3078.3 | — |
| SECONDARY Pharmakokinetic Parameters Based on FVIIa Activity: Vss (Distribution Volume at Steady State) |
5396.9; 9597.0; 5538.7; 6696.7 | — |
| SECONDARY Immunogenicity (Inhibitor Development) |
0; 0; 0; 0; 0; 0 | — |
| SECONDARY Biochemistry: ALAT (Alanine Aminotransferase) |
26.0; 32.8; 30.6; 39.3; 24.2; 30.1 | — |
| SECONDARY Biochemistry: Creatinine |
66.9; 67.2; 63.6; 67.7; 60.0; 66.9 | — |
| SECONDARY Haematology: Haemoglobin |
13.9; 14.7; 14.2; 14.2; 14.6; 13.8 | — |
| SECONDARY Haematology: Red Cell Count |
5.0; 5.4; 5.3; 5.1; 5.7; 5.3 | — |
| SECONDARY Haematology: Packed Cell Volume |
41.6; 43.7; 42.2; 42.4; 44.0; 41.6 | — |
| SECONDARY Haematology: White Cell Count |
6.7; 6.3; 7.2; 6.9; 6.6; 5.8 | — |
| SECONDARY Haematology: Platelet Count |
259.8; 253.8; 250.8; 276.1; 272.5; 259.0 | — |
Summary
This trial is conducted in Africa, Asia, Europe, Japan, and North and South America.
The aim of this trial is to evaluate the safety and efficacy of activated recombinant human factor VII analogue (vatreptocog alfa (activated)) in haemophilia patients with inhibitors.
Eligibility Criteria
Inclusion Criteria
- 12 years of age or older (at least 18 years in Croatia, France and United Kingdom (UK))
- Clinical diagnosis of congenital haemophilia A or B with a current positive inhibitor titre and a known peak inhibitor of above 5 Bethesda units (BU) (present or in the past) to human FVIII or IX and known antihuman FVIII or IX anamnestic response
- Minimum of 2 joint bleeds (haemarthroses of ankles, knees, or elbows) requiring haemostatic drug treatment within the previous 6 months, or at least 4 joint bleeds (hemarthroses of ankles, knees, or elbows) requiring haemostatic drug treatment within the previous 12 months at trial entry
Exclusion Criteria
- Known allergy to rFVIIa, and/or suspected allergy to trial product
- Platelet count lower than 50, 000 mm^3 based on medical records at trial entry (visit 1)
- Any clinical signs or history of thromboembolic events
- Advanced atherosclerotic disease
- Severe liver disease based on medical records within the past 12 months at trial entry (Visit 1), as defined by alanine aminotransferase (ALAT) above 3 times the upper limit of normal reference range
- Known active pseudo tumours (documented bleeding requiring treatment within the last 3 months
- Subject had any (major) surgical procedure in the 30 days prior to screening into the trial. a. Catheter, ports and dental extractions do not count as surgeries and will not exclude the subject
Data sourced from ClinicalTrials.gov (NCT00486278). 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.