Haemophilia B MedDRA version: 19.0 Level: LLT Classification code 10060614 Term: Hemophilia B (Factor IX) System Organ Class: 100000004850
Conditions
Interventions
Product Name: IB1001
Product Code: IB1001
Pharmaceutical Form: Powder and solvent for solution for injection
INN or Proposed INN: TRENONACOG ALFA
Sponsors
Aptevo Europe Limited
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Patient must be willing to give written Institutional Review Board (IRB)/ Independent Ethics Committee (IEC)-approved informed consent, make the required study visits, and follow instructions while enrolled in the study. 2. Severe (factor IX activity =2 U/dL) hemophilia B subjects on-demand therapy with a minimum of 3 bleeding episodes over the preceding 6 months or 6 bleeding episodes over the preceding 12 months; subjects on prophylaxis with a bleeding pattern as above demonstrated prior to starting prophylaxis 3. Immunocompetent (CD4 count >400/mm3) and not receiving immune modulating or chemotherapeutic agents 4. Previously treated patients with a minimum of 150 exposure days to a factor IX preparation 5. Platelet count at least 150,000/mm3 6. Liver function: alanine transaminase [ALT] and aspartate transaminase [AST] =2 times the upper limit of the normal range 7. Total bilirubin =1.5 times the upper limit of the normal range 8. Renal function: serum creatinine =1.25 times the upper limit of the normal range 9. Willingness to participate in the trial for up to 12-15 months 10. European Union (EU), Israel, and India: Age of at least 12 years and body weight of =40 kilograms to participate in any PK Study or the Surgical Sub-study; age of at least 12 years for the prophylaxis and on-demand components of the Treatment Phase and Continuation Study. Subjects in France less than 18 years of age will not be included in any PK study. United States (US): Age of at least 12 years and body weight of =40 kilograms to participate in any PK Study or the Surgical Sub-study; age of at least 5 years for the prophylaxis and on-demand components of the Treatment Phase and Continuation Study 11. Hemoglobin =7 g/dL at the time of the blood draw Are the trial subjects under 18? yes Number of subjects for this age range: 15 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 65 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. History of factor IX inhibitor =0.6 Bethesda units (BU) 2. Existence of another coagulation disorder 3. Evidence of thrombotic disease, fibrinolysis, or disseminated intravascular coagulation (DIC) 4. Use of an investigational drug within 30 days prior to study entry 5. On medications that could impact hemostasis, such as aspirin 6. Hypersensitivity to the active substance or to any of the excipients in the investigational products 7. Known allergic reaction to hamster proteins 8. History of poor compliance, a serious medical or social condition, or any other circumstance that, in the opinion of the investigator, would interfere with participation or compliance with the study protocol 9. History of adverse reaction to either plasma-derived factor IX or recombinant factor IX that interfered with the subject’s ability to treat bleeding episodes with a factor IX product
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the safety, pharmacokinetics (PK) and efficacy with respect to breakthrough bleeding during prophylaxis and with respect to control of haemorrhaging in both the prophylaxis and on demand groups of IB1001 in subjects with haemophilia B; Secondary Objective: 1. To evaluate markers of thrombogenicity including D-dimer, fragment 1 +2 (F1+2), and thrombin-antithrombin III complex (TAT) 2. To obtain information on subject response to an intravenously delivered recombinant factor IX (rFIX) product in terms of tolerance and compliance 3. To estimate the frequency of spontaneous bleeding in subjects with haemophilia B treated on demand 4. To evaluate the ability of IB1001 to provide coverage against bleeding under surgical circumstances, as well as to manage breakthrough bleeding during prophylaxis 5. To evaluate the long-term safety and efficacy of IB1001 ; Primary end point(s): Safety: acute effects associate with infusion, and inhibitor development PK: Cmax, AUC, t1/2, clearance, recovery, Vd Efficacy: breakthrough bleeding during prophylaxis and on demand groups for IB1001 in subjects with haemophilia B ; Timepoint(s) of evaluation of this end point: Safety: - Acute effects are defined as adverse events (AEs) which occur within the first 72 hours after administration of a study product - Inhibitor development: prior to the first infusion of IB1001, after the first 5 infusions (for subjects on prophylaxis), and every 3 months (+/- 2 weeks) thereafter PK: parameters determined for each separate PK assessment period during 72 hours after single infusion Efficacy: diaries maintained by all subjects throughout treatment document breakthrough bleeding and the subjects assessment efficacy of IB1001 to treat breakthrough ( | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Plasma levels of D-dimer, F1+2, TAT 2. Tolerance: defined as the ability to use IB1001 without AE + compliance 3. Frequency of spontaneous bleeding in subjects treated on demand 4. Surgeon estimation of blood loss at the time of surgery + post-surgery haemostasis 5. Evaluate long term safety and efficacy ; Timepoint(s) of evaluation of this end point: 1. During the BeneFix/IB1001 PK study within the first 24 hours after PK infusion dose 2 and 3. Diaries maintained by all subjects during treatment with IB1001 and evaluated during follow-up visits 4, At the time of the surgery and post-surgery (12 and 24 hours) 5. Subjects are seen every 3 months during continuation phase | — |
Countries
France, India, Israel, Italy, Poland, United Kingdom, United States
Contacts
Public ContactClinical Trial Unit
Aptevo Europe Limited
Outcome results
None listed