Hemophilia B
Conditions
Brief summary
This study will investigate the pharmacokinetics (PK), efficacy, and safety of rIX-FP for the routine prophylaxis of bleeding episodes in male Chinese previously treated patients (PTPs) with hemophilia B (FIX activity of ≤ 2%). In addition to the scheduled rIX-FP prophylaxis regimen, subjects may also receive rIX-FP episodic (on-demand) treatment for breakthrough bleeding episodes and rIX-FP for the prophylaxis and treatment of bleeding in emergency surgical procedures.
Interventions
BIOLOGICALRecombinant fusion protein linking coagulation factor IX with albumin (rIX-FP)
Lyophilized powder for solution for intravenous injection
Sponsors
CSL Behring
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
No minimum to 70 Years
Healthy volunteers
No
Inclusion criteria
* Male Chinese subjects aged ≤ 70 years * Subjects with documented severe or moderately severe hemophilia B (FIX activity of ≤ 2%) * Subjects have received FIX products for ≥ 150 exposure days (EDs) (subjects aged ≥ 6 years) or ≥ 50 EDs (subjects aged \< 6 years) * Subjects have no confirmed prior history of FIX inhibitor formation
Exclusion criteria
* Known hypersensitivity (allergic reaction or anaphylaxis) to any FIX product or hamster protein. * Known congenital or acquired coagulation disorder other than congenital FIX deficiency. * Currently receiving intravenous (IV) immunomodulating agents such as immunoglobulin or chronic systemic corticosteroid treatment. * Currently receiving a long-acting recombinant FIX treatment such as coagulation factor IX (recombinant), Fc fusion protein (Alprolix®). * Use of traditional or herbal Chinese medicine(s) with an impact on hemophilia, including coagulation, within 28 days before Day 1 and / or refusal to abstain from these during the study until the end of the subject's participation in the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incremental recovery (IR) (plasma FIX activity) | Before, and at 30 minutes after the end of, rIX-FP infusion on Day 1 | — |
| Maximum plasma concentration (Cmax) | Before, and up to 336 hours after the end of, rIX-FP infusion on Day 1 | — |
| Terminal elimination half-life (t1/2) of rIX-FP | Before, and up to 336 hours after the end of, rIX-FP infusion on Day 1 | — |
| Area under the concentration-time curve (AUC) | Before, and up to 336 hours after the end of, rIX-FP infusion on Day 1 | AUC from time zero to the last measurable concentration (plasma FIX activity) (AUC0-last), and AUC from time zero extrapolated to infinity (AUC0-inf). |
| Clearance (Cl) of rIX-FP | Before, and up to 336 hours after the end of, rIX-FP infusion on Day 1 | — |
| Annualized spontaneous bleeding rate (AsBR) | Up to 18 months | AsBR for treated bleeding episodes, by prophylaxis regimen and overall |
| Number of subjects who develop an inhibitor to FIX | Up to 18 months after rIX-FP infusion | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of area under the concentration-time curve extrapolated (%AUCExt) | Before, and up to 336 hours after the end of, rIX-FP infusion on Day 1 and at Week 26 (Repeat PK) | — |
| Area under the first moment versus time curve extrapolated to infinity (AUMC0-∞) | Before, and up to 336 hours after the end of, rIX-FP infusion on Day 1 and at Week 26 (Repeat PK) | — |
| Mean residence time (MRT) | Before, and up to 336 hours after the end of, rIX-FP infusion on Day 1 and at Week 26 (Repeat PK) | — |
| Apparent volume of distribution during the terminal phase (Vz) | Before, and up to 336 hours after the end of, rIX-FP infusion on Day 1 and at Week 26 (Repeat PK) | — |
| Apparent volume of distribution at steady-state (Vss) | Before, and up to 336 hours after the end of, rIX-FP infusion on Day 1 and at Week 26 (Repeat PK) | — |
| Time to reach Cmax (Tmax) | Before, and up to 336 hours after the end of, rIX-FP infusion on Day 1 and at Week 26 (Repeat PK) | — |
| Elimination rate constant (λz) | Before, and up to 336 hours after the end of, rIX-FP infusion on Day 1 and at Week 26 (Repeat PK) | — |
| Incremental recovery (IR) (plasma FIX activity) - Repeat PK | Before, and at 30 minutes after the end of, rIX-FP infusion at Week 26 | — |
| Maximum plasma concentration (Cmax) - Repeat PK | Before, and up to 336 hours after the end of, rIX-FP infusion at Week 26 | — |
| Terminal elimination half-life (t1/2) of rIX-FP - Repeat PK | Before, and up to 336 hours after the end of, rIX-FP infusion at Week 26 | — |
| Area under the concentration-time curve (AUC) - Repeat PK | Before, and up to 336 hours after the end of, rIX-FP infusion at Week 26 | AUC from time zero to the last measurable concentration (plasma FIX activity) (AUC0-last), and AUC from time zero extrapolated to infinity (AUC0-inf). |
| Clearance (Cl) of rIX-FP - Repeat PK | Before, and up to 336 hours after the end of, rIX-FP infusion at Week 26 | — |
| Annualized bleeding rate (ABR) | Up to 18 months after rIX-FP infusion | ABR for treated, untreated, and both treated and untreated bleeding episodes (spontaneous bleeding, traumatic bleeding, unknown bleeding, and total bleeding episodes), by prophylaxis regimen and overall |
| Annualized joint bleeding rate (AjBR) | Up to 18 months after rIX-FP infusion | AjBR for treated, untreated, and both treated and untreated bleeding episodes, by prophylaxis regimen and overall |
| Clinical evaluation of hemostatic efficacy for major bleeding episodes | Up to 18 months after rIX-FP infusion | The investigator will rate the efficacy of the rIX-FP treatment for major bleeding episodes based on a hemostatic efficacy four point rating scale of "excellent, good, moderate or no efficacy", by prophylaxis regimen and overall |
| Change in target joints | At baseline and up to 18 months after rIX-FP infusion | — |
| Consumption of rIX-FP - number of rIX-FP infusions (doses) | Up to 18 months after rIX-FP infusion | Consumption of rIX-FP expressed as number of rIX-FP infusions (doses), for the prophylaxis regimens, episodic (on-demand) treatment for bleeding episodes (if any), and total (overall) treatment |
| Consumption of rIX-FP - IU/kg per subject per month | Up to 18 months after rIX-FP infusion | Consumption of rIX-FP expressed as total amount (IU/kg) per subject per month, for the prophylaxis regimens, episodic (on-demand) treatment for bleeding episodes (if any), and total (overall) treatment |
| Consumption of rIX-FP - IU/kg per subject per year | Up to 18 months after rIX-FP infusion | Consumption of rIX-FP expressed as total amount (IU/kg) per subject per year, for the prophylaxis regimens, episodic (on-demand) treatment for bleeding episodes (if any), and total (overall) treatment. |
| Number of bleeding episodes requiring rIX-FP to achieve hemostasis | Up to 18 months after rIX-FP infusion | Number of bleeding episodes requiring 1, ≤ 2, or \> 2 infusions (doses) of rIX-FP to achieve hemostasis |
| Percentage of bleeding episodes requiring rIX-FP to achieve hemostasis | Up to 18 months after rIX-FP infusion | Percentage of bleeding episodes requiring 1, ≤ 2, or \> 2 infusions (doses) of rIX-FP to achieve hemostasis |
| Number of subjects who develop antibodies against rIX-FP | Before, and up to 18 months after, rIX-FP infusion | — |
| Number of subjects who develop antibodies against Chinese hamster ovary host cell protein | Before, and up to 18 months after, rIX-FP infusion | — |
| The number of subjects with treatment emergent adverse events (TEAEs) related to rIX-FP | Up to 18 months after rIX-FP infusion | — |
| The percentage of subjects with treatment emergent adverse events (TEAEs) related to rIX-FP | Up to 18 months after rIX-FP infusion | — |
Countries
China
Contacts
STUDY_DIRECTORClinical Program Director
CSL Behring
Outcome results
None listed