Congenital Hemophilia A
Conditions
Brief summary
For bridging the available global clinical data of rVIII-SingleChain, with the Chinese population, the aim of this study in China is to investigate the pharmacokinetics (PK) of rVIII-SingleChain after an initial and repeat dose and to assess efficacy and safety during 2 to 3 times weekly prophylaxis treatment with rVIII-SingleChain in male Chinese PTPs with severe hemophilia A (FVIII activity less than \[\<\] 1%).
Interventions
BIOLOGICALRecombinant single-chain factor VIII (rVIII-SingleChain)
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
0 Days to 65 Years
Healthy volunteers
No
Inclusion criteria
* • Male Chinese participants \<= 65 years of age. * • Participants with severe hemophilia A (FVIII activity \< 1%). * • Participants who have received FVIII products for \>= 150 EDs (\>= 6 years of age) or \>= 50 EDs (\< 6 years of age).
Exclusion criteria
* • Known hypersensitivity (allergic reaction or anaphylaxis) to any FVIII product or hamster protein. * • Known congenital or acquired coagulation disorder other than congenital FVIII deficiency. * • Currently receiving intravenous (IV) immunomodulating agents such as immunoglobulin or chronic systemic corticosteroid treatment. * • Receiving any cryoprecipitate, whole blood, or plasma within 30 days before administration of rVIII-SingleChain. * • 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 participant's participation in the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incremental Recovery (IR) of rVIII-SingleChain | Before, and at 30 minutes after the end of, rVIII-SingleChain administration on Day 1 | — |
| Maximum Concentration (Cmax) of rVIII-SingleChain | Before, and up to 72 hours (participants ≥ 12 years ) and 48 hours (participants < 12 years) after rVIII-SingleChain administration on Day 1 | — |
| Area Under the Plasma Concentration Time Curve from Time Zero to the Last Measurable Concentration (AUC0-last) of rVIII-SingleChain | Before, and up to 72 hours (participants ≥ 12 years ) and 48 hours (participants < 12 years) after rVIII-SingleChain administration on Day 1 | — |
| Area Under the Plasma Concentration Time Curve from Time Zero to Infinity (AUC0-inf) of rVIII-SingleChain | Before, and up to 72 hours (participants ≥ 12 years ) and 48 hours (participants < 12 years) after rVIII-SingleChain administration on Day 1 | — |
| Half-life (t1/2) of rVIII-SingleChain | Before, and up to 72 hours (participants ≥ 12 years ) and 48 hours (participants < 12 years) after rVIII-SingleChain administration on Day 1 | — |
| Clearance (Cl) of rVIII-SingleChain | Before, and up to 72 hours (participants ≥ 12 years ) and 48 hours (participants < 12 years) after rVIII-SingleChain administration on Day 1 | — |
| Annualized Spontaneous Bleeding Rate (AsBR) | Up to 29 weeks after rVIII-SingleChain administration | AsBR for treated bleeding episodes |
| Number of participants who develop FVIII inhibitors | During routine rVIII-SingleChain prophylaxis dosing, up to 29 weeks after rVIII-SingleChain administration. | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to reach maximum concentration (Tmax) of rVIII-SingleChain | Before, and up to 72 hours (participants ≥ 12 years ) and 48 hours (participants < 12 years) after rVIII-SingleChain administration on Day 1 | — |
| Last Concentration (Clast) of rVIII-SingleChain | Before, and up to 72 hours (participants ≥ 12 years ) and 48 hours (participants < 12 years) after rVIII-SingleChain administration on Day 1 | Last observed quantifiable plasma concentration |
| IR (participants ≥ 12 years of age) of rVIII-SingleChain (Repeat pharmacokinetic [PK]) | Before, and at up to 72 hours after the end of, rVIII-SingleChain infusion at Week 28 | — |
| Cmax (participants ≥ 12 years of age) of rVIII-SingleChain (Repeat PK) | Before, and at up to 72 hours after the end of, rVIII-SingleChain infusion at Week 28 | — |
| AUC0-last of rVIII-SingleChain (Repeat PK) | Before, and at up to 72 hours after the end of, rVIII-SingleChain infusion at Week 28 | — |
| AUC0-inf of rVIII-SingleChain (Repeat PK) | Before, and at up to 72 hours after the end of, rVIII-SingleChain infusion at Week 28 | — |
| t1/2 of rVIII-SingleChain (participants ≥ 12 years of age) (Repeat PK) | Before, and at up to 72 hours after the end of, rVIII-SingleChain infusion at Week 28 | — |
| Cl of rVIII-SingleChain (participants ≥ 12 years of age) (Repeat PK) | Before, and at up to 72 hours after the end of, rVIII-SingleChain infusion at Week 28 | — |
| Annualized Bleeding Rate (ABR) | Up to 29 weeks after rVIII-SingleChain administration | Total ABR for treated, untreated, and both treated and untreated bleeding episodes (spontaneous, traumatic, and unknown cause) |
| Hemostatic Efficacy for Major and Nonmajor Bleeding Episodes | Up to 29 weeks after rVIII-SingleChain administration | The investigator will rate the efficacy of the rVIII-SingleChain treatment for major and nonmajor bleeding episodes based on a hemostatic efficacy four point rating scale of "excellent, good, moderate or no efficacy". |
| Consumption of rVIII-SingleChain - number of infusions (doses) | Up to 29 weeks after rVIII-SingleChain administration | — |
| Consumption of rVIII-SingleChain - IU/kg per participant per month | Up to 29 weeks after rVIII-SingleChain administration | rVIII-SingleChain consumption (IU/kg) per participant per month, for the weekly regimen, on-demand treatment, and total treatment. |
| Consumption of rVIII-SingleChain - IU/kg per participant per year | Up to 29 weeks after rVIII-SingleChain administration | rVIII-SingleChain consumption (IU/kg) per participant per year, for the weekly regimen, on-demand treatment, and total treatment. |
| Number of bleeding episodes requiring rVIII-SingleChain to achieve hemostasis | Up to 29 weeks after rVIII-SingleChain administration | Number of bleeding episodes requiring 1, \<= 2, or \> 2 infusions (doses) of rVIII-SingleChain to achieve hemostasis |
| Percentage of bleeding episodes requiring rVIII-SingleChain to achieve hemostasis | Up to 29 weeks after rVIII-SingleChain administration | Percentage of bleeding episodes requiring 1, \<= 2, or \> 2 infusions (doses) of rVIII-SingleChain to achieve hemostasis |
| Number of participants who develop noninhibitory antibodies against rVIII-SingleChain | Before, and up to 29 weeks after, rVIII-SingleChain administration | — |
| Number of participants who develop antibodies against Chinese hamster ovary host cell protein | Before, and up to 29 weeks after, rVIII-SingleChain administration | — |
| Number of participants with Treatment-emergent Adverse Events (TEAEs), including related TEAEs, and serious adverse events (SAEs) | Up to 33 weeks after rVIII-SingleChain administration | — |
| Percentage of participants with TEAEs, including related TEAEs, and serious adverse events (SAEs) | Up to 33 weeks after rVIII-SingleChain administration | — |
| Number of TEAEs (events) | Up to 33 weeks after rVIII-SingleChain administration | — |
Countries
China
Contacts
STUDY_DIRECTORStudy Director
CSL Behring
Outcome results
None listed