Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
rFVIIIFc · 4 trials · 2 indications
AUCinf is area under the concentration-time curve from time zero to infinity. Results were summarized overall for 15K rFVIIIFc 1000 IU/vial and 6000 IU/Vial (PK2).
Incremental Recovery is defined as the increase in the circulating FVIII activity in international unit per deciliter (IU/dL) per unit dose administered in international unit per kilogram (IU/kg) (IU/dL per IU/kg). Results were summarized overall for 15K rFVIIIFc 1000 IU/vial and 6000 IU/Vial (PK2).
A positive/confirmed inhibitor result occurs when a participant has a value \>=0.6 BU/mL by central laboratory testing using Nijmegen-modified Bethesda assay, that is confirmed on re-testing of a separate sample collected \>=2 weeks after the initial sample. Confirmed inhibitor development was based on all participants who had reached \>=10 EDs and had \>=1 inhibitor test performed at or beyond this milestone or who had an inhibitor. Exposure day (ED) is a 24-hour period in which participant received \>=1 dose of rFVIIIFc injections. Participants who did not develop an inhibitor but reached the milestone number of EDs were included in the denominator during calculation of percentage. Additionally, any participant who developed an inhibitor following the initial rFVIIIFc administration was included in the numerator and denominator during calculation of percentage.
An inhibitor test result greater than or equal to (\>=) 0.6 Bethesda units per milliliter (BU/mL), identified and confirmed by re-testing of a second sample obtained within 2 to 4 weeks, was considered positive. Both tests were to be performed using the Nijmegen-modified Bethesda Assay by the central laboratory. Data was summarized by treatment regimen for participants from 997HA301/997HA307/997HA309 combined and by age cohort (\<6 years and 6 to \<12 years old) and treatment regimen for participants from 8HA02PED per planned analysis. Participants were included in summary of more than 1 treatment regimen if their regimen changed during study.
Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0 - ∞).
The rise in FVIII activity in IU/dL per unit dose administered in IU/kg (IR, K value), as estimated from the FVIII activity data.
| Arm | Type | Description |
|---|---|---|
| rFVIIIFc (15K scale) 1000 IU vial | EXPERIMENTAL | Single injection of rFVIIIFc (current 2K scale) followed by 2 single injections of rFVIIIFc (15K scale) 1000 IU vial at PK2 and PK3 timepoints. Participants will be on prophylaxis regimen along with treatment for bleeding episodes for 26 weeks of treatment period using the rFVIIIFc (15K scale) 1000 IU vial. |
| rFVIIIFc (15K scale) 6000 IU vial | EXPERIMENTAL | Single injection of rFVIIIFc (current 2K scale) followed by 2 single injections of rFVIIIFc high strength vial (15K scale) at PK2 and PK3 timepoints. Participants will be on prophylaxis regimen along with treatment for bleeding episodes for 26 weeks of treatment period using the rFVIIIFc (15K scale) 6000 IU vial. |
| rFVIIIFc | EXPERIMENTAL | Participants were to receive rFVIIIFc as follows- Prophylaxis regimen (PR): rFVIIIFc 25-80 international units per kilogram (IU/kg), at 3- to 5-day intervals until participant reached greater than or equal to (\>=) 50 exposure days (ED: 24-hour period in which \>=1 injection/dose of rFVIIIFc was given), or study withdrawal/end of study. Adjustments to dose/dosing interval was done as needed by investigator; Treatment with an optional ER (Episodic regimen) can be initiated before PR at investigators discretion; ITI: rFVIIIFc 200 IU/kg, daily for participants who, after exposure to rFVIIIFc, had positive high titer inhibitor (\>=5.00 Bethesda Units per milliliter \[BU/mL\]) or positive low titer inhibitor (\>=0.60 and \<5.00 BU/mL) and had poorly controlled bleeding despite increased rFVIIIFc doses, or required bypassing agent to treat bleeding. |
| On-Demand | EXPERIMENTAL | The individual dose of rFVIIIFc to treat bleeding episodes will be based on participant's clinical condition, type and severity of the bleeding event, and if indicated, Factor VIII (FVIII) levels. |
| Prophylaxis | EXPERIMENTAL | Tailored prophylaxis, Weekly prophylaxis or Personalized prophylaxis available. |
| rFVIIIFc 1000 / 3000 PK Assessment | EXPERIMENTAL | A single intravenous (IV) injection of rFVIIIFc 50 IU/kg at a strength of 1000 IU/vial followed by a single IV injection of rFVIIIFc 50 IU/kg at a strength of 3000 IU/vial. Following the PK assessment, participants will receive either an episodic (on-demand) regimen with doses between 20 and 50 IU/kg based on the severity of the bleeding episode, or 1 of 2 prophylactic regimens: 50 IU/kg every 3 to 5 days or 65 IU/kg weekly. Participants will be allowed to switch from one regimen to another if approved by the Investigator. |
| rFVIIIFc 3000 / 1000 PK Assessment | EXPERIMENTAL | A single IV injection of rFVIIIFc 50 IU/kg at a strength of 3000 IU/vial followed by a single IV injection of rFVIIIFc 50 IU/kg at a strength of 1000 IU/vial. Following the PK assessment, participants will receive either an episodic (on-demand) regimen with doses between 20 and 50 IU/kg based on the severity of the bleeding episode, or 1 of 2 prophylactic regimens: 50 IU/kg every 3 to 5 days or 65 IU/kg weekly. Participants will be allowed to switch from one regimen to another if approved by the Investigator. |
| Name | Type | Description |
|---|---|---|
| rFVIIIFc | BIOLOGICAL | As per arm description |
Key Inclusion Criteria: * Have severe hemophilia A, defined as \<1 IU/dL (\<1%) endogenous FVIII as determined by one-stage clotting assay from the central laboratory at Screening. * Previously treated subject, defined as having at least 150 documented prior exposure days (EDs) to any recombinant a...
rFVIIIFc is an investigational recombinant factor VIII Fc fusion protein being studied for the prevention and treatment of bleeding episodes in people with hemophilia A, including severe hemophilia A. It is in clinical development for this hematology indication.
rFVIIIFc is being developed by Sanofi, a global biopharmaceutical company traded on the New York Stock Exchange under the ticker SNY. The company is conducting clinical trials to evaluate the safety and efficacy of this investigational therapy for hemophilia A.
rFVIIIFc is in Phase 3 clinical development. Multiple Phase 3 trials have been completed, including studies in previously treated patients and previously untreated males with severe hemophilia A. It remains an investigational agent and is not yet approved.
rFVIIIFc has been studied in several completed clinical trials. NCT01454739 evaluated long-term safety and efficacy in 240 participants with hemophilia A. NCT02234323 studied safety and efficacy in 108 previously untreated males with severe hemophilia A. NCT02502149 assessed pharmacokinetics and safety in 24 participants.
rFVIIIFc is a recombinant factor VIII Fc fusion protein. It is also known by the name efmoroctocog alfa. This alternative name may be used in some clinical or regulatory contexts to refer to the same investigational therapy for hemophilia A.
rFVIIIFc is a recombinant fusion protein that replaces missing or defective clotting factor VIII in people with hemophilia A. By providing functional factor VIII, it aims to restore the blood clotting cascade and help prevent or control bleeding episodes.