Hemophilia A
Conditions
Keywords
On-demand treatment; Hemostatic Efficacy Assessments; Factor VIII recovery; Factor VIII Inhibitor; Chinese
Brief summary
This study will evaluate the safety and efficacy of on-demand treatment with Xyntha in Chinese hemophilia A subjects.
Interventions
BIOLOGICALXyntha
Xyntha for on-demand treatment of bleeding episodes were according to investigator prescription during the 6 months observation period. The recovery assessed by determining the Factor VIII (FVIII) concentration (FVIII:C) levels in individual subjects at the initial and final visits. The dose of Xyntha for recovery assessments is: single 50 IU/kg (±5 IU/kg) IV bolus infusion. All Xyntha administrations occurred in the clinic (hospital).
Sponsors
Pfizer
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
6 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Subjects equal or more than 6 years of age with mild, moderate or severe hemophilia A (FVIII activity: more than 5%, 1-5%, or less than 1%, respectively) * Subjects with previous exposure to FVIII replacement therapy * If human immunodeficiency virus (HIV) positive, documented cluster of differentiation (CD4) count more than 200/µL within 6 months of study entry
Exclusion criteria
* Diagnosed with any bleeding disorder in addition to hemophilia A * Current FVIII inhibitor or history of FVIII inhibitor (defined as positive result of the reporting laboratory) * Subject has no history of exposure to FVIII products (previously untreated patient \[PUP\]) * Subject is currently utilizing primary FVIII prophylaxis * Subjects anticipating elective surgery that may be planned to occur in the 6 months following study entry * Treated with immunomodulatory therapy within 30 days prior to study entry or planned use for the duration of their study participation * Participated in another investigational drug or device study within 30 days prior to study entry or planned participation for the duration of their study participation * Subjects with a known hypersensitivity to hamster protein * Significant hepatic or renal impairment (alanine aminotransferase \[ALT\] and aspartate aminotransferase \[AST\] \>5 x upper limit of normal \[ULN\], bilirubin \>2 mg/dL or serum creatinine \>1.25 x ULN) * Prothrombin Time \>1.5 x ULN * Platelet count \<80,000 / µL * Pregnant or breastfeeding women * Unwilling or unable to follow the terms of the protocol * Any condition which may compromise the subject's ability to comply with and/or perform study-related activities or that poses a clinical contraindication to study participation, in the opinion of the Investigator or Sponsor
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Investigator Hemostatic Efficacy Assessment 8 Hours Post Infusion | 8 hours post infusion | The Investigator Hemostatic Efficacy Assessment was based on a 4-point rating scale (Excellent = 1: definite pain relief or improvement in signs of bleeding, with no additional infusion, Good = 2: definite pain relief or improvement in signs of bleeding, Moderate = 3: probable or slight improvement, No Response = 4: no improvement at all between infusions). |
| Number of Participants With Factor VIII (FVIII) Inhibitor Development | Day 1 and Month 6 or Early Termination Visit | Incidence of FVIII inhibitor was defined as any result determined as positive at local laboratory, and confirmed at central laboratory. Incidence was stratified by participant exposure history: Minimally Treated Patients (MTPs): those who had received at least 1 prior FVIII infusion, and \<= 100 documented Exposure Days (EDs), while Previously Treated Patients (PTPs): those who had received \>100 documented prior EDs. When number of prior EDs for an individual was not known to be at least 100, participants were included in the MTP population. |
| Investigator Hemostatic Efficacy Assessment 24 Hours Post Infusion | 24 hours post infusion | The Investigator Hemostatic Efficacy Assessment was based on a 4-point rating scale (Excellent = 1: definite pain relief or improvement in signs of bleeding, with no additional infusion, Good = 2: definite pain relief or improvement in signs of bleeding, Moderate = 3: probable or slight improvement, No Response = 4: no improvement at all between infusions). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Thrombosis | Baseline up to 6 months | — |
| Number of Participants With Thrombosis Allergic-Type Reactions | Baseline up to 6 months | — |
| FVIII Recovery : Change From Baseline in FVIII Concentration | Day 1 and Month 6 or Early Termination Visit | FVIII recovery was assessed by evaluating the change in FVIII concentration at 6 months compared to baseline. |
| Number of Participants With Less Than Expected Therapeutic Effect (LETE) | 24 hours after each of 2 successive infusion, up to 6 months | The incidence of LETE, defined for on-demand treatment as no response after each of 2 successive infusions within 24 hours for the same bleeding event in the absence of confounding factors. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Frequency of Xyntha Infusions Required Per Hemorrhage | Day 1 to Month 6 or Early Termination Visit | The mean frequency of Xyntha infusions per hemorrhage was calculated as total number of injections throughout the study divided by total number of hemorrhagic events. |
| Average Dose of Xyntha Infusions Required Per Hemorrhage | Day 1 to Month 6 or Early Termination Visit | The average dose of Xyntha per hemorrhagic event was calculated as total dose of Xyntha throughout the study (in IU) divided by total number of hemorrhage incidence. |
Countries
China
Participant flow
Recruitment details
Participants were recruited in China from September 2008 to December 2009.
Participants by arm
| Arm | Count |
|---|---|
| Xyntha Participants received on-demand treatments with Xyntha (which occurred each time a participant experienced bleeding episode during the active phase of the study) according to investigator's prescription over a 6-month (calendar day) period. A single 50 International Unit (IU)/kg (+/-5 IU/kg) intravenous (IV) bolus infusion of Xyntha was given for recovery assessments. | 53 |
| Total | 53 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 3 |
| Overall Study | Lost to Follow-up | 1 |
Baseline characteristics
| Characteristic | Xyntha |
|---|---|
| Age, Continuous | 23.2 Years STANDARD_DEVIATION 10 |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 53 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 13 / 53 |
| serious Total, serious adverse events | 9 / 53 |
Outcome results
Primary
Investigator Hemostatic Efficacy Assessment 24 Hours Post Infusion
The Investigator Hemostatic Efficacy Assessment was based on a 4-point rating scale (Excellent = 1: definite pain relief or improvement in signs of bleeding, with no additional infusion, Good = 2: definite pain relief or improvement in signs of bleeding, Moderate = 3: probable or slight improvement, No Response = 4: no improvement at all between infusions).
Time frame: 24 hours post infusion
Population: The FAS consisted of all participants who were treated and had at least 1 evaluable efficacy assessment after treatment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Xyntha | Investigator Hemostatic Efficacy Assessment 24 Hours Post Infusion | 1.74 Units on a scale | Standard Deviation 0.61 |
Primary
Investigator Hemostatic Efficacy Assessment 8 Hours Post Infusion
The Investigator Hemostatic Efficacy Assessment was based on a 4-point rating scale (Excellent = 1: definite pain relief or improvement in signs of bleeding, with no additional infusion, Good = 2: definite pain relief or improvement in signs of bleeding, Moderate = 3: probable or slight improvement, No Response = 4: no improvement at all between infusions).
Time frame: 8 hours post infusion
Population: The Full Analysis Set (FAS) consisted of all participants who were treated and had at least 1 evaluable efficacy assessment after treatment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Xyntha | Investigator Hemostatic Efficacy Assessment 8 Hours Post Infusion | 1.86 Units on a scale | Standard Deviation 0.65 |
Primary
Number of Participants With Factor VIII (FVIII) Inhibitor Development
Incidence of FVIII inhibitor was defined as any result determined as positive at local laboratory, and confirmed at central laboratory. Incidence was stratified by participant exposure history: Minimally Treated Patients (MTPs): those who had received at least 1 prior FVIII infusion, and \<= 100 documented Exposure Days (EDs), while Previously Treated Patients (PTPs): those who had received \>100 documented prior EDs. When number of prior EDs for an individual was not known to be at least 100, participants were included in the MTP population.
Time frame: Day 1 and Month 6 or Early Termination Visit
Population: The Safety Set (SS) consisted of all participants who had taken at least 1 dose of investigational drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Xyntha | Number of Participants With Factor VIII (FVIII) Inhibitor Development | MTP (n=36) | 6 Participants |
| Xyntha | Number of Participants With Factor VIII (FVIII) Inhibitor Development | PTP (n=17) | 1 Participants |
Secondary
FVIII Recovery : Change From Baseline in FVIII Concentration
FVIII recovery was assessed by evaluating the change in FVIII concentration at 6 months compared to baseline.
Time frame: Day 1 and Month 6 or Early Termination Visit
Population: The FAS consisted of all participants who were treated and had at least 1 evaluable efficacy assessment after treatment. Participants with missing data were not included.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Xyntha | FVIII Recovery : Change From Baseline in FVIII Concentration | -0.11 IU/dL per IU/kg | Standard Deviation 0.45 |
p-value: 0.12t-test, 2 sided
Secondary
Number of Participants With Less Than Expected Therapeutic Effect (LETE)
The incidence of LETE, defined for on-demand treatment as no response after each of 2 successive infusions within 24 hours for the same bleeding event in the absence of confounding factors.
Time frame: 24 hours after each of 2 successive infusion, up to 6 months
Population: The FAS consisted of all participants who were treated and had at least 1 evaluable efficacy assessment after treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Xyntha | Number of Participants With Less Than Expected Therapeutic Effect (LETE) | 0 Participants |
Secondary
Number of Participants With Thrombosis
Time frame: Baseline up to 6 months
Population: The SS consisted of all participants who had taken at least 1 dose of investigational drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Xyntha | Number of Participants With Thrombosis | 0 Participants |
Secondary
Number of Participants With Thrombosis Allergic-Type Reactions
Time frame: Baseline up to 6 months
Population: The Safety Set (SS) consisted of all participants who had taken at least 1 dose of investigational drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Xyntha | Number of Participants With Thrombosis Allergic-Type Reactions | 1 Participants |
Other Pre-specified
Average Dose of Xyntha Infusions Required Per Hemorrhage
The average dose of Xyntha per hemorrhagic event was calculated as total dose of Xyntha throughout the study (in IU) divided by total number of hemorrhage incidence.
Time frame: Day 1 to Month 6 or Early Termination Visit
Population: The FAS consisted of all participants who were treated and had at least 1 evaluable efficacy assessment after treatment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Xyntha | Average Dose of Xyntha Infusions Required Per Hemorrhage | 1226.28 Dose/Bleed (IU) | Standard Deviation 1208.49 |
Other Pre-specified
Frequency of Xyntha Infusions Required Per Hemorrhage
The mean frequency of Xyntha infusions per hemorrhage was calculated as total number of injections throughout the study divided by total number of hemorrhagic events.
Time frame: Day 1 to Month 6 or Early Termination Visit
Population: The FAS consisted of all participants who were treated and had at least 1 evaluable efficacy assessment after treatment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Xyntha | Frequency of Xyntha Infusions Required Per Hemorrhage | 1.16 Infusions | Standard Deviation 0.72 |