Hemophilia A, Severe Hemophilia A
Conditions
Brief summary
This multicenter, open-label, phase 3 extension study will investigate the safety and efficacy of rVIII-SingleChain for prophylaxis and on-demand treatment of bleeding episodes in at least 200 previously treated patients (PTPs) with severe congenital hemophilia A and previous exposure to FVIII products who achieve at least 100 exposure days (EDs) to rVIII-SingleChain in this study, as well as in previously untreated patients (PUPs) with no previous exposure to any FVIII product who achieve at least 50 EDs to rVIII-SingleChain in this study. A substudy (open to both PTPs and PUPs) will investigate the use of rVIII-SingleChain in surgery. A substudy (open to PUPs who develop an inhibitor to rVIII-SingleChain) will investigate the use of rVIII-SingleChain in immune tolerance induction (ITI) therapy.
Interventions
BIOLOGICALrVIII-SingleChain
Recombinant single-chain coagulation factor VIII
Sponsors
CSL Behring
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Healthy volunteers
No
Inclusion criteria
PTPs: * Males of any age who have been diagnosed with severe congenital hemophilia A (FVIII activity levels \< 1%) and who participated in a previous CSL-sponsored clinical study with rVIII-SingleChain. * Males 0 to \<65 years age who have been diagnosed with severe congenital hemophilia A (FVIII activity levels \< 1%), who have at least 50 EDs to any FVIII product, and who are not currently enrolled in a CSL-sponsored clinical study with rVIII-SingleChain. PUPs: * Males 0 to \<18 years of who have been diagnosed with severe congenital hemophilia A (FVIII activity levels \< 1%) * No prior exposure to any Factor VIII product (with the exception of short-term use of blood products). ITI substudy: * PUPs who have developed a confirmed inhibitor to rVIII-SingleChain in the main study.
Exclusion criteria
* Known or suspected hypersensitivity to rVIII-SingleChain or to any excipients of rVIII-SingleChain or Chinese hamster ovary (CHO) proteins. * Currently receiving a therapy not permitted during the study. * Serum creatinine \> 2 x upper limit of normal, alanine aminotransferase or aspartate aminotransferase \> 5 x upper limit of normal at Screening (if specified) * Any first-order family (eg, siblings) history of FVIII inhibitors * For PTPs not rolling over directly from a CSL-sponsored clinical study with rVIII-SingleChain: any history of or current FVIII inhibitors
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Inhibitor Formation to FVIII in Previously Treated Patients (PTPs) With 100 Exposure Days (EDs) to CSL627 | At the closest visit after 100 EDs (up to 5 years). | — |
| Number of Previously Untreated Patients (PUPs) With High-titer Inhibitor Formation to FVIII With at Least 50 EDs to CSL627 | At the closest visit after 50 EDs (up to 5 years). | High-titer inhibitor is defined as an inhibitor titer of ≥ 5 Bethesda units/mL. |
| Percent Treatment Success for Major Bleeding Episodes in PUPs | Up to 5 years | Percentage of major bleeding episodes treated successfully where treatment success for a bleeding episode is defined as a rating of excellent or good on the investigator's clinical assessment of hemostatic efficacy 4-point scale excellent, good, moderate or poor/no response. Major bleeding episodes are defined as bleeding episodes for which a subject is required to seek treatment at the hemophilia center or that threatens the subject's life or loss of limb. |
| Annualized Spontaneous Bleeding Rate in PUPs | Up to 5 years | The annualized spontaneous bleeding rate for PUPs taking prophylaxis and on-demand treatment regimens. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean On-demand Dose Administered of CSL627 | Up to 5 years | — |
| Mean Prophylaxis Dose Administered of CSL627 | Up to 5 years | — |
| Mean Total Amount of CSL627 Administered During Surgery Period in PTPs | Day of surgery up to 336 hours post-surgery | — |
| Total Amount of CSL627 Administered During Surgery Period in PUPs | Day of surgery up to 336 hours post-surgery | — |
| Hemostatic Efficacy of rVIII-SingleChain for PTPs and PUPs Who Undergo Surgery | From the start of surgery through the post-operative recovery (generally up to 14 days after surgery) | The investigator will rate the efficacy of the rVIII-SingleChain treatment during surgery based on a hemostatic efficacy four point rating scale of excellent, good, moderate or poor/no response. |
| Incidence of Inhibitor Formation to FVIII in PTPs After 10 EDs and After 50 EDs | Up to 5 years | — |
| Percentage of PTPs and PUPs Developing Antibodies Against CSL627 | PTPs: At the closest visit after 100 EDs (up to 5 years). PUPs: At the closest visit after 50 EDs (up to 5 years). | — |
| Percentage of Bleeding Episodes Treated Successfully in PTPs | Up to 5 years | Percentage of bleeding episodes treated successfully where treatment success for a bleeding episode is defined as a rating of excellent or good on the investigator's clinical assessment of hemostatic efficacy 4-point scale excellent, good, moderate or poor/no response. |
| Number of PUPs With High-titer Inhibitor Formation to FVIII After 10 EDs With CSL627 | At the closest visit after 10 EDs (up to 5 years) | High-titer inhibitor is defined as an inhibitor titer of ≥ 5 Bethesda units/mL. |
| Number of PUPs With Low-titer Inhibitor Formation to FVIII After 10 EDs and After 50 EDs With CSL627 | At the closest visit after 10 and after 50 EDs (up to 5 years) | Low-titer inhibitor is defined as an inhibitor titer of less than 5 Bethesda units/mL. |
| Incidence of Total Inhibitor Formation to FVIII in PUPs | Up to 5 years | — |
| Percent Treatment Success for Non-major Bleeding Episodes in PUPs | Up to 5 years | Percentage of bleeding episodes treated successfully where treatment success for a bleeding episode is defined as a rating of excellent or good on the investigator's clinical assessment of hemostatic efficacy 4-point scale excellent, good, moderate or poor/no response. Non-major bleeding episodes are those not requiring treatment at the hemophilia center or not threatening subject's life or loss of limb. |
| Percentage of PUPs With Clinically Significant Abnormal Vital Signs Values After First Infusion of CSL627 | Up to 6 hours after first infusion | Vital signs assessments include heart rate, blood pressure, and body temperature. Clinical significance of an abnormality will be assessed by the investigator. |
| Percentage of PUPs With Treatment-emergent Clinically Significant Abnormal Vital Signs Values | Up to 5 years | Vital signs assessments include heart rate, blood pressure, and body temperature. Clinical significance of an abnormality will be assessed by the investigator. |
| Percentage of PTPs and PUPs Developing Antibodies to Chinese Hamster Ovary (CHO) Proteins | PTPs: At the closest visit after 100 EDs (up to 5 years). PUPs: At the closest visit after 50 EDs (up to 5 years). | — |
| Annualized Bleeding Rate in PTPs and PUPs | Up to 5 years | The annualized bleeding rate for PTPs and PUPs taking prophylaxis and on-demand treatment regimens |
| Percentage of Bleeding Episodes Requiring 1, 2, 3, or > 3 Injections of CSL627 to Achieve Hemostasis in PTPs and PUPs | Up to 5 years | — |
| Mean Number of On-demand Infusions of CSL627 | Up to 5 years | — |
Countries
Australia, Austria, Canada, Czechia, France, Georgia, Germany, Hungary, Ireland, Italy, Japan, Lebanon, Malaysia, Netherlands, Philippines, Poland, Portugal, Romania, South Africa, Spain, Switzerland, Thailand, Ukraine, United Kingdom, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Previously Treated Patients (PTPs) The investigator will assign subjects to either prophylaxis or on-demand treatment regimens for rVIII-SingleChain by intravenous injection. The investigator will determine the rVIII-SingleChain dose and dosing schedule for the subject based upon the subject's pharmacokinetic (PK) profile, rVIII-SingleChain PK data, previous FVIII treatment regimen, and bleeding phenotype, if available.
rVIII-SingleChain: Recombinant single-chain coagulation factor VIII | 222 |
| Previously Untreated Patients (PUPs) The investigator will assign subjects to either prophylaxis or on-demand treatment regimens for rVIII-SingleChain by intravenous injection. The investigator will determine the rVIII-SingleChain dose and dosing schedule at their discretion, taking into consideration the World Federation of Hemophilia (WFH) guidelines, the type of bleeding episode, location of the bleeding, subject's age, and other disease characteristics.
rVIII-SingleChain: Recombinant single-chain coagulation factor VIII | 24 |
| Total | 246 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 4 | 1 |
| Overall Study | Death | 1 | 0 |
| Overall Study | Lack of Efficacy | 1 | 0 |
| Overall Study | Lost to Follow-up | 1 | 0 |
| Overall Study | Patient moving | 1 | 0 |
| Overall Study | Patient relocated overseas | 1 | 1 |
| Overall Study | Patient traveling | 1 | 0 |
| Overall Study | Patient went to other country | 1 | 0 |
| Overall Study | Physician Decision | 3 | 3 |
| Overall Study | Protocol Violation | 1 | 0 |
| Overall Study | Withdrawal by Subject | 10 | 0 |
Baseline characteristics
| Characteristic | Previously Treated Patients (PTPs) | Previously Untreated Patients (PUPs) | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 95 Participants | 24 Participants | 119 Participants |
| Age, Categorical >=65 years | 1 Participants | 0 Participants | 1 Participants |
| Age, Categorical Between 18 and 65 years | 126 Participants | 0 Participants | 126 Participants |
| Age, Continuous PTPs | 22.5 years STANDARD_DEVIATION 14.55 | — | 22.5 years STANDARD_DEVIATION 14.55 |
| Age, Continuous PUPs | — | 1.4 years STANDARD_DEVIATION 1.18 | 1.4 years STANDARD_DEVIATION 1.18 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 10 Participants | 1 Participants | 11 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 212 Participants | 23 Participants | 235 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 50 Participants | 2 Participants | 52 Participants |
| Race (NIH/OMB) Black or African American | 12 Participants | 7 Participants | 19 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) White | 158 Participants | 15 Participants | 173 Participants |
| Region of Enrollment Australia | 11 participants | 0 participants | 11 participants |
| Region of Enrollment Austria | 6 participants | 0 participants | 6 participants |
| Region of Enrollment Canada | 1 participants | 0 participants | 1 participants |
| Region of Enrollment Czechia | 2 participants | 0 participants | 2 participants |
| Region of Enrollment France | 7 participants | 0 participants | 7 participants |
| Region of Enrollment Georgia | 5 participants | 0 participants | 5 participants |
| Region of Enrollment Germany | 10 participants | 0 participants | 10 participants |
| Region of Enrollment Hungary | 2 participants | 0 participants | 2 participants |
| Region of Enrollment Ireland | 5 participants | 0 participants | 5 participants |
| Region of Enrollment Italy | 5 participants | 4 participants | 9 participants |
| Region of Enrollment Japan | 7 participants | 0 participants | 7 participants |
| Region of Enrollment Lebanon | 9 participants | 3 participants | 12 participants |
| Region of Enrollment Malaysia | 13 participants | 2 participants | 15 participants |
| Region of Enrollment Netherlands | 9 participants | 3 participants | 12 participants |
| Region of Enrollment Philippines | 18 participants | 0 participants | 18 participants |
| Region of Enrollment Poland | 36 participants | 0 participants | 36 participants |
| Region of Enrollment Portugal | 2 participants | 3 participants | 5 participants |
| Region of Enrollment Romania | 4 participants | 0 participants | 4 participants |
| Region of Enrollment South Africa | 14 participants | 8 participants | 22 participants |
| Region of Enrollment Spain | 6 participants | 0 participants | 6 participants |
| Region of Enrollment Switzerland | 1 participants | 0 participants | 1 participants |
| Region of Enrollment Thailand | 10 participants | 0 participants | 10 participants |
| Region of Enrollment Ukraine | 17 participants | 0 participants | 17 participants |
| Region of Enrollment United Kingdom | 1 participants | 0 participants | 1 participants |
| Region of Enrollment United States | 21 participants | 1 participants | 22 participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 222 Participants | 24 Participants | 246 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 1 / 222 | 0 / 24 |
| other Total, other adverse events | 130 / 222 | 23 / 24 |
| serious Total, serious adverse events | 23 / 222 | 14 / 24 |
Outcome results
Primary
Annualized Spontaneous Bleeding Rate in PUPs
The annualized spontaneous bleeding rate for PUPs taking prophylaxis and on-demand treatment regimens.
Time frame: Up to 5 years
Population: EP. This endpoint was analyzed for PUPs only.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| CSL627: Previously Treated Patients (PTPs) | Annualized Spontaneous Bleeding Rate in PUPs | On-demand | 1.9 Number of Spontaneous bleeds per year | Standard Deviation 2.252 |
| CSL627: Previously Treated Patients (PTPs) | Annualized Spontaneous Bleeding Rate in PUPs | Prophylaxis | 4.04 Number of Spontaneous bleeds per year | Standard Deviation 6.374 |
Primary
Incidence of Inhibitor Formation to FVIII in Previously Treated Patients (PTPs) With 100 Exposure Days (EDs) to CSL627
Time frame: At the closest visit after 100 EDs (up to 5 years).
Population: Safety population (SP) - comprised all the Enrolled Population who received at least 1 dose of rVIII-SingleChain (CSL627) during the study for any reason.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| CSL627: Previously Treated Patients (PTPs) | Incidence of Inhibitor Formation to FVIII in Previously Treated Patients (PTPs) With 100 Exposure Days (EDs) to CSL627 | 0 percentage of paticipants |
Primary
Number of Previously Untreated Patients (PUPs) With High-titer Inhibitor Formation to FVIII With at Least 50 EDs to CSL627
High-titer inhibitor is defined as an inhibitor titer of ≥ 5 Bethesda units/mL.
Time frame: At the closest visit after 50 EDs (up to 5 years).
Population: SP
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| CSL627: Previously Treated Patients (PTPs) | Number of Previously Untreated Patients (PUPs) With High-titer Inhibitor Formation to FVIII With at Least 50 EDs to CSL627 | 5 participants |
Primary
Percent Treatment Success for Major Bleeding Episodes in PUPs
Percentage of major bleeding episodes treated successfully where treatment success for a bleeding episode is defined as a rating of excellent or good on the investigator's clinical assessment of hemostatic efficacy 4-point scale excellent, good, moderate or poor/no response. Major bleeding episodes are defined as bleeding episodes for which a subject is required to seek treatment at the hemophilia center or that threatens the subject's life or loss of limb.
Time frame: Up to 5 years
Population: Efficacy population (EP) - comprised all subjects in the Safety Population who received at least 1 dose of rVIII-SingleChain (CSL627) for either routine prophylaxis treatment or on-demand treatment during the study. This endpoint was analyzed for PUPs only.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| CSL627: Previously Treated Patients (PTPs) | Percent Treatment Success for Major Bleeding Episodes in PUPs | 100 percentage of treatment success |
Secondary
Annualized Bleeding Rate in PTPs and PUPs
The annualized bleeding rate for PTPs and PUPs taking prophylaxis and on-demand treatment regimens
Time frame: Up to 5 years
Population: EP
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| CSL627: Previously Treated Patients (PTPs) | Annualized Bleeding Rate in PTPs and PUPs | On-demand | 28.32 Number of bleeds per year | Standard Deviation 29.014 |
| CSL627: Previously Treated Patients (PTPs) | Annualized Bleeding Rate in PTPs and PUPs | Prophylaxis | 2.84 Number of bleeds per year | Standard Deviation 4.981 |
| CSL627: Previously Untreated Patients (PUPs) | Annualized Bleeding Rate in PTPs and PUPs | On-demand | 5.12 Number of bleeds per year | Standard Deviation 5.331 |
| CSL627: Previously Untreated Patients (PUPs) | Annualized Bleeding Rate in PTPs and PUPs | Prophylaxis | 5.94 Number of bleeds per year | Standard Deviation 7.705 |
Secondary
Hemostatic Efficacy of rVIII-SingleChain for PTPs and PUPs Who Undergo Surgery
The investigator will rate the efficacy of the rVIII-SingleChain treatment during surgery based on a hemostatic efficacy four point rating scale of excellent, good, moderate or poor/no response.
Time frame: From the start of surgery through the post-operative recovery (generally up to 14 days after surgery)
Population: Surgery population - comprised all subjects in the Safety Population who received at least 1 dose of rVIII-SingleChain for surgical prophylaxis
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| CSL627: Previously Treated Patients (PTPs) | Hemostatic Efficacy of rVIII-SingleChain for PTPs and PUPs Who Undergo Surgery | Excellent | 28 Number of surgeries |
| CSL627: Previously Treated Patients (PTPs) | Hemostatic Efficacy of rVIII-SingleChain for PTPs and PUPs Who Undergo Surgery | Good | 4 Number of surgeries |
| CSL627: Previously Treated Patients (PTPs) | Hemostatic Efficacy of rVIII-SingleChain for PTPs and PUPs Who Undergo Surgery | Moderate | 0 Number of surgeries |
| CSL627: Previously Treated Patients (PTPs) | Hemostatic Efficacy of rVIII-SingleChain for PTPs and PUPs Who Undergo Surgery | Poor/No response | 0 Number of surgeries |
| CSL627: Previously Untreated Patients (PUPs) | Hemostatic Efficacy of rVIII-SingleChain for PTPs and PUPs Who Undergo Surgery | Poor/No response | 0 Number of surgeries |
| CSL627: Previously Untreated Patients (PUPs) | Hemostatic Efficacy of rVIII-SingleChain for PTPs and PUPs Who Undergo Surgery | Excellent | 3 Number of surgeries |
| CSL627: Previously Untreated Patients (PUPs) | Hemostatic Efficacy of rVIII-SingleChain for PTPs and PUPs Who Undergo Surgery | Moderate | 0 Number of surgeries |
| CSL627: Previously Untreated Patients (PUPs) | Hemostatic Efficacy of rVIII-SingleChain for PTPs and PUPs Who Undergo Surgery | Good | 0 Number of surgeries |
Secondary
Incidence of Inhibitor Formation to FVIII in PTPs After 10 EDs and After 50 EDs
Time frame: Up to 5 years
Population: SP
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| CSL627: Previously Treated Patients (PTPs) | Incidence of Inhibitor Formation to FVIII in PTPs After 10 EDs and After 50 EDs | after 10 EDs | 0 percentage of participants |
| CSL627: Previously Treated Patients (PTPs) | Incidence of Inhibitor Formation to FVIII in PTPs After 10 EDs and After 50 EDs | after 50 EDs | 0 percentage of participants |
Secondary
Incidence of Total Inhibitor Formation to FVIII in PUPs
Time frame: Up to 5 years
Population: SP
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| CSL627: Previously Treated Patients (PTPs) | Incidence of Total Inhibitor Formation to FVIII in PUPs | 50.0 percentage of participants |
Secondary
Mean Number of On-demand Infusions of CSL627
Time frame: Up to 5 years
Population: EP. This endpoint analyzes PTPs and PUPs that received on-demand treatment.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| CSL627: Previously Treated Patients (PTPs) | Mean Number of On-demand Infusions of CSL627 | per participant per month | 6.26 Number of infusions | Standard Deviation 4.778 |
| CSL627: Previously Treated Patients (PTPs) | Mean Number of On-demand Infusions of CSL627 | per participant per year | 75.18 Number of infusions | Standard Deviation 57.335 |
| CSL627: Previously Untreated Patients (PUPs) | Mean Number of On-demand Infusions of CSL627 | per participant per month | 1.23 Number of infusions | Standard Deviation 1.296 |
| CSL627: Previously Untreated Patients (PUPs) | Mean Number of On-demand Infusions of CSL627 | per participant per year | 14.75 Number of infusions | Standard Deviation 15.547 |
Secondary
Mean On-demand Dose Administered of CSL627
Time frame: Up to 5 years
Population: EP. This endpoint analyzes PTPs and PUPs that received on-demand treatment.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| CSL627: Previously Treated Patients (PTPs) | Mean On-demand Dose Administered of CSL627 | per participant per month | 210.39 IU/kg | Standard Deviation 188.106 |
| CSL627: Previously Treated Patients (PTPs) | Mean On-demand Dose Administered of CSL627 | per participant per year | 2524.69 IU/kg | Standard Deviation 2257.278 |
| CSL627: Previously Untreated Patients (PUPs) | Mean On-demand Dose Administered of CSL627 | per participant per month | 41.93 IU/kg | Standard Deviation 44.643 |
| CSL627: Previously Untreated Patients (PUPs) | Mean On-demand Dose Administered of CSL627 | per participant per year | 503.16 IU/kg | Standard Deviation 535.712 |
Secondary
Mean Prophylaxis Dose Administered of CSL627
Time frame: Up to 5 years
Population: EP. This endpoint analyzes PTPs and PUPs that received prophylaxis treatment.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| CSL627: Previously Treated Patients (PTPs) | Mean Prophylaxis Dose Administered of CSL627 | per participant per year | 4571.35 IU/kg | Standard Deviation 1560.944 |
| CSL627: Previously Treated Patients (PTPs) | Mean Prophylaxis Dose Administered of CSL627 | per participant per month | 380.95 IU/kg | Standard Deviation 130.079 |
| CSL627: Previously Untreated Patients (PUPs) | Mean Prophylaxis Dose Administered of CSL627 | per participant per month | 389.30 IU/kg | Standard Deviation 243.191 |
| CSL627: Previously Untreated Patients (PUPs) | Mean Prophylaxis Dose Administered of CSL627 | per participant per year | 4671.54 IU/kg | Standard Deviation 2918.288 |
Secondary
Mean Total Amount of CSL627 Administered During Surgery Period in PTPs
Time frame: Day of surgery up to 336 hours post-surgery
Population: Surgery population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CSL627: Previously Treated Patients (PTPs) | Mean Total Amount of CSL627 Administered During Surgery Period in PTPs | 51663.0 IU | Standard Deviation 62033.25 |
Secondary
Number of PUPs With High-titer Inhibitor Formation to FVIII After 10 EDs With CSL627
High-titer inhibitor is defined as an inhibitor titer of ≥ 5 Bethesda units/mL.
Time frame: At the closest visit after 10 EDs (up to 5 years)
Population: SP
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| CSL627: Previously Treated Patients (PTPs) | Number of PUPs With High-titer Inhibitor Formation to FVIII After 10 EDs With CSL627 | 4 participants |
Secondary
Number of PUPs With Low-titer Inhibitor Formation to FVIII After 10 EDs and After 50 EDs With CSL627
Low-titer inhibitor is defined as an inhibitor titer of less than 5 Bethesda units/mL.
Time frame: At the closest visit after 10 and after 50 EDs (up to 5 years)
Population: SP
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| CSL627: Previously Treated Patients (PTPs) | Number of PUPs With Low-titer Inhibitor Formation to FVIII After 10 EDs and After 50 EDs With CSL627 | after 50 EDs | 0 participants |
| CSL627: Previously Treated Patients (PTPs) | Number of PUPs With Low-titer Inhibitor Formation to FVIII After 10 EDs and After 50 EDs With CSL627 | after 10 EDs | 4 participants |
Secondary
Percentage of Bleeding Episodes Requiring 1, 2, 3, or > 3 Injections of CSL627 to Achieve Hemostasis in PTPs and PUPs
Time frame: Up to 5 years
Population: EP
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| CSL627: Previously Treated Patients (PTPs) | Percentage of Bleeding Episodes Requiring 1, 2, 3, or > 3 Injections of CSL627 to Achieve Hemostasis in PTPs and PUPs | 1 infusion | 71.5 Percentage of treated bleeds |
| CSL627: Previously Treated Patients (PTPs) | Percentage of Bleeding Episodes Requiring 1, 2, 3, or > 3 Injections of CSL627 to Achieve Hemostasis in PTPs and PUPs | 2 infusions | 14.8 Percentage of treated bleeds |
| CSL627: Previously Treated Patients (PTPs) | Percentage of Bleeding Episodes Requiring 1, 2, 3, or > 3 Injections of CSL627 to Achieve Hemostasis in PTPs and PUPs | 3 infusions | 6.9 Percentage of treated bleeds |
| CSL627: Previously Treated Patients (PTPs) | Percentage of Bleeding Episodes Requiring 1, 2, 3, or > 3 Injections of CSL627 to Achieve Hemostasis in PTPs and PUPs | >3 infusions | 6.3 Percentage of treated bleeds |
| CSL627: Previously Untreated Patients (PUPs) | Percentage of Bleeding Episodes Requiring 1, 2, 3, or > 3 Injections of CSL627 to Achieve Hemostasis in PTPs and PUPs | >3 infusions | 3.5 Percentage of treated bleeds |
| CSL627: Previously Untreated Patients (PUPs) | Percentage of Bleeding Episodes Requiring 1, 2, 3, or > 3 Injections of CSL627 to Achieve Hemostasis in PTPs and PUPs | 1 infusion | 77.5 Percentage of treated bleeds |
| CSL627: Previously Untreated Patients (PUPs) | Percentage of Bleeding Episodes Requiring 1, 2, 3, or > 3 Injections of CSL627 to Achieve Hemostasis in PTPs and PUPs | 3 infusions | 5.4 Percentage of treated bleeds |
| CSL627: Previously Untreated Patients (PUPs) | Percentage of Bleeding Episodes Requiring 1, 2, 3, or > 3 Injections of CSL627 to Achieve Hemostasis in PTPs and PUPs | 2 infusions | 11.4 Percentage of treated bleeds |
Secondary
Percentage of Bleeding Episodes Treated Successfully in PTPs
Percentage of bleeding episodes treated successfully where treatment success for a bleeding episode is defined as a rating of excellent or good on the investigator's clinical assessment of hemostatic efficacy 4-point scale excellent, good, moderate or poor/no response.
Time frame: Up to 5 years
Population: EP
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| CSL627: Previously Treated Patients (PTPs) | Percentage of Bleeding Episodes Treated Successfully in PTPs | 87.1 Percentage of treated bleeding events |
Secondary
Percentage of PTPs and PUPs Developing Antibodies Against CSL627
Time frame: PTPs: At the closest visit after 100 EDs (up to 5 years). PUPs: At the closest visit after 50 EDs (up to 5 years).
Population: SP
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| CSL627: Previously Treated Patients (PTPs) | Percentage of PTPs and PUPs Developing Antibodies Against CSL627 | 15.3 percentage of participants |
| CSL627: Previously Untreated Patients (PUPs) | Percentage of PTPs and PUPs Developing Antibodies Against CSL627 | 70.8 percentage of participants |
Secondary
Percentage of PTPs and PUPs Developing Antibodies to Chinese Hamster Ovary (CHO) Proteins
Time frame: PTPs: At the closest visit after 100 EDs (up to 5 years). PUPs: At the closest visit after 50 EDs (up to 5 years).
Population: SP
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| CSL627: Previously Treated Patients (PTPs) | Percentage of PTPs and PUPs Developing Antibodies to Chinese Hamster Ovary (CHO) Proteins | 0 percentage of participants |
| CSL627: Previously Untreated Patients (PUPs) | Percentage of PTPs and PUPs Developing Antibodies to Chinese Hamster Ovary (CHO) Proteins | 0 percentage of participants |
Secondary
Percentage of PUPs With Clinically Significant Abnormal Vital Signs Values After First Infusion of CSL627
Vital signs assessments include heart rate, blood pressure, and body temperature. Clinical significance of an abnormality will be assessed by the investigator.
Time frame: Up to 6 hours after first infusion
Population: SP. This endpoint was analyzed for PUPs only.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| CSL627: Previously Treated Patients (PTPs) | Percentage of PUPs With Clinically Significant Abnormal Vital Signs Values After First Infusion of CSL627 | 0 percentage of participants |
Secondary
Percentage of PUPs With Treatment-emergent Clinically Significant Abnormal Vital Signs Values
Vital signs assessments include heart rate, blood pressure, and body temperature. Clinical significance of an abnormality will be assessed by the investigator.
Time frame: Up to 5 years
Population: SP. This endpoint was analyzed for PUPs only.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| CSL627: Previously Treated Patients (PTPs) | Percentage of PUPs With Treatment-emergent Clinically Significant Abnormal Vital Signs Values | 0 percentage of participants |
Secondary
Percent Treatment Success for Non-major Bleeding Episodes in PUPs
Percentage of bleeding episodes treated successfully where treatment success for a bleeding episode is defined as a rating of excellent or good on the investigator's clinical assessment of hemostatic efficacy 4-point scale excellent, good, moderate or poor/no response. Non-major bleeding episodes are those not requiring treatment at the hemophilia center or not threatening subject's life or loss of limb.
Time frame: Up to 5 years
Population: EP. This endpoint was analyzed for PUPs only.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| CSL627: Previously Treated Patients (PTPs) | Percent Treatment Success for Non-major Bleeding Episodes in PUPs | 92.1 percentage of treated bleeding events |
Secondary
Total Amount of CSL627 Administered During Surgery Period in PUPs
Time frame: Day of surgery up to 336 hours post-surgery
Population: Surgery population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| CSL627: Previously Treated Patients (PTPs) | Total Amount of CSL627 Administered During Surgery Period in PUPs | Participant 1 | 15693 IU |
| CSL627: Previously Treated Patients (PTPs) | Total Amount of CSL627 Administered During Surgery Period in PUPs | Participant 2 | 5631 IU |
| CSL627: Previously Treated Patients (PTPs) | Total Amount of CSL627 Administered During Surgery Period in PUPs | Participant 3 | 7330 IU |