E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Previously treated patients (PTPs) with severe (FIX level < 1%) or moderately severe (FIX level ≤ 2%) hemophilia B. |
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E.1.1.1 | Medical condition in easily understood language |
Previously treated patients with severe or moderately severe hemophilia B. |
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E.1.1.2 | Therapeutic area | Diseases [C] - Blood and lymphatic diseases [C15] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10018939 |
E.1.2 | Term | Haemophilia B (Factor IX) |
E.1.2 | System Organ Class | 10010331 - Congenital, familial and genetic disorders |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To further evaluate the safety, immunogenicity, and hemostatic efficacy of BAX 326 in those subjects who completed pivotal study 250901 or Pediatric Study 251101, until BAX 326 is licensed in subject's country or until the total accumulation of at least 100 exposure days (EDs) of treatment with BAX 326, whichever occurs last
To monitor incremental recovery of BAX 326 over time
To evaluate changes in health-related quality of life (HR QoL) and health resource use |
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E.2.2 | Secondary objectives of the trial |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• The subject and/or legal representative has/have voluntartily provided signed informed consent.
• Subject has completed Baxter clinical study 250901 or Pediatric Study 251101.
• Subject was 12 to 65 years old at the time of screening for 250901 study or <12 years old at the time of screening for Pediatric Study 251101.
• Subject has not developed an inhibitory FIX antibody during Baxter clinical study 250901 or Pediatric Study 251101.
• Subject is human immunodeficiency (HIV) negative or is HIV+ with a viral load < 200 particles/μL ~ <400,000 copies/mL
• Subject is immunocompetent as evidenced by a CD4 count ≥ 200 cells/mm3.
• If female of childbearing potential, subject presents with a negative pregnancy test and agrees to continue employing adequate birth control measures for the duration of the study.
• Subject is willing and able to comply with the requirements of the protocol.
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E.4 | Principal exclusion criteria |
• The subject received factor IX product(s) other than BAX 326 upon completion of Baxter pivotal study 250901 or Pediatric Study 251101.
• The subject has been diagnosed with an acquired hemostatic defect other than hemophilia B.
• For subjects transferring from Pivotal Study 250901: The subject’s weight is < 35 kg or > 120 kg.
• The subject’s platelet count is < 100,000/mL.
• The subject has an abnormal renal function (serum creatinine > 1.5 times the upper limit of normal).
• The subject has active hepatic disease with alanine aminotransferase (ALT) or aspartate aminotransferase (AST) levels ≥ 5 times the upper limit of normal.
• The subject is scheduled to receive during the course of the study, an immunomodulating drug (e.g. corticosteroid agents at a dose equivalent to hydrocortisone greater than 10 mg/day, or α-interferon) other than anti-retroviral chemotherapy.
• The subject has a clinically significant medical, psychiatric, or cognitive illness, or recreational drug/alcohol use that, in the opinion of the investigator, would affect subject’s safety or compliance.
• The subject is planned to take part in any other clinical study, with the exception of BAX 326 Surgery study as described in this protocol, during the course of the Continuation Study.
• The subject is a member of the team conducting this study or is in a dependent relationship with one of the study team members. Dependent relationships include close relatives (i.e., children, partner/spouse, siblings, parents) as well as employees of the investigator or site personnel conducting the study. |
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E.5 End points |
E.5.1 | Primary end point(s) |
• Adverse events possibly or probably related to IP |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
Safety and Immunogenicity
• Development of inhibitory and total binding antibodies to FIX.
• Development of antibodies to CHO proteins and rFurin.
• Occurrence of severe allergic reactions, e.g. anaphylaxis.
• Occurrence of thrombotic events
• Clinically significant changes in routine laboratory parameters (hematology and clinical chemistry), and vital signs.
PK
• Incremental recovery (IR) over time.
Hemostatic efficacy
• Treatment of bleeding episodes: number of infusions per bleeding episode, overall hemostatic efficacy rating at resolution of bleed.
• Prophylaxis: annualized bleeding rate.
• Consumption of BAX326:
- Number of infusions and weight-adjusted consumption per month and per year;
- Weight-adjusted consumption per event (prophylaxis and on-demand).
Health Related Quality of Life and Pharmacoeconomic Parameters
Changes in the following HR QoL parameters and health resource use:
• For subjects who are between 2 to 7 years of age (at the time of screening for Study 251101):
- Generic: PedsQL™ (Parent-proxy versions: age group 2-4 years and age group 5-7 years)
- Health resource use (hospitalizations, emergency room visits, doctor office visits, etc.)
• For subjects who are between 8 to 11 years of age (at the time of screening for Study 251101):
- Disease-specific: Haemo-QoL, short version
- Generic: PedsQL™ Child version
- Health resource use (hospitalizations, emergency room visits, doctor office visits, etc.)
• For subjects who are between 12 and 16 years of age (at the time of screening for Study 250901) the following questioninaires will be used:
- Disease-specific: Haemo-QoL short version
- Generic: PedsQL™
- Health utility: EQ-5D
- General pain assessment through a visual analog scale (VAS)
- Health resource use
• For subjects aged 17 years and older (at the time of screening for Study 250901) the following questionnaires will be used:
- Disease-specific: Haem-A-QoL
- Generic: SF-36
- Health Utility: EQ-5D
- General pain assessment through a visual analog scale (VAS)
- Health resource use
Safety and Immunogenicity
Pharmacokinetics
Hemostatic efficacy
health related Quality of Life and Health Resource Use |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | Yes |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
Immunogenicity, hemostatic efficacy |
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E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 20 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Argentina |
Brazil |
Chile |
Colombia |
Japan |
Russian Federation |
Ukraine |
United States |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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Not applicable (licensure of BAX326 in subject's respective country). |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 5 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 4 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |