Hemophilia A
Conditions
Keywords
hemophilia A, Xyntha, ReFacto, moroctocog alfa, bleeding disorder
Brief summary
This study will be investigating the safety and efficacy of Xyntha (moroctocog alfa (AF-CC)) in male patients less than 6 years old. Annualized bleeding rates and physician / caregiver assessments of responses to treatment will be characterized. FVIII inhibitor levels will be assessed throughout the study.
Detailed description
The study was terminated on 22 Sept 2009 due to competition with another Wyeth study for a similar patient population. The decision to terminate the trial was not based on any safety issues.
Interventions
BIOLOGICALMoroctocog alfa
Patients will receive Moroctocog alfa according to their investigator's prescription.
Sponsors
Wyeth is now a wholly owned subsidiary of Pfizer
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
0 Years to 5 Years
Healthy volunteers
No
Inclusion criteria
* Male patients less than 6 years of age with moderately severe to severe hemophilia A (FVIII less than or equal to 2%). * Treatment history of less than 50 exposure days to prior recombinant or plasma-derived FVIII replacement products. * Not receiving treatment for HIV or hepatitis infection, or the patient is on a stable antiviral regimen at the time of enrollment in the study.
Exclusion criteria
* Presence of any bleeding disorder in addition to hemophilia A. * Inhibitor titer of greater than or equal to 5 Bethesda Units (BU) at screening. * Treated with immunomodulatory therapy during the screening period * Treatment history of more than 5 exposure days (ED) to Xyntha. * Known hypersensitivity to hamster protein.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Low Recovery LETE | Baseline to 24 months or early withdrawal. | The LETE could be considered lower than expected recovery of FVIII in the opinion of the investigator following infusion of Xyntha in the absence of confounding factors. |
| Percentage of Participants With Factor VIII (FVIII) Inhibitor Development | Baseline to 24 months or early withdrawal. | Incidence of inhibitor development was defined as any result determined positive at a central laboratory (Bethesda inhibitor titer of \>=0.6 BU/mL) using Nijmegen modification of the Bethesda assay. |
| Percentage of Participants With Less Than Expected Therapeutic Effects (LETE) in the On-Demand Setting | Baseline to 24 months or early withdrawal. | LETE in the on-demand setting was based on the response to the treatment of a bleeding episode. LETE in the on-demand setting occurred if the participant recorded 2 successive No Response ratings (indicated there was no improvement at all between infusions or during the 24 hour interval following an infusion, or condition worsened) after 2 successive Xyntha infusions, respectively. The infusions was to be administered within 24 hours (=\<24 hours) of each other for the treatment of the same bleeding event in the absence of confounding factor. |
| Percentage of Participants With LETE in the Prophylaxis Setting | Baseline to 24 months or early withdrawal. | The LETE in the prophylaxis setting was the occurrence of a bleed. LETE in the prophylaxis setting occurred if there was a spontaneous bleed within 48 hours (=\<48 hours) after a regularly scheduled prophylactic dose of Xyntha (which was not used to treat a bleed) in the absence of confounding factors. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean Annualized Bleed Rate (ABR) | Baseline to 24 months or early withdrawal. | An annualized bleeding rate (ABR) for each participant was calculated as the number of bleeds requiring administration of FVIII replacement product (taken from the electronic Infusion Log Diary), divided by his total therapy duration (in days), and then multiplied by 365.25. |
| Number of Xyntha Infusions Needed to Treat Each New Bleed | Baseline to 24 months or early withdrawal. | The data from the electronic Infusion Log Diary plus the Test Article case report form (CRF) was used to determine the number of infusions administered to treat a bleed. This was calculated by adding the initial 'for a new bleed' (on demand) infusion to any subsequent (on demand) infusions for the (same) 'previously treated bleed'. An on-demand infusion for a 'previously treated bleed' was counted toward the bleed with the most recent start time prior to that infusion. |
| Response to First On-demand Xyntha Treatment for All New Bleeds as Assessed by the Caregiver | Baseline to 24 months or early withdrawal | A 4-point response scale to be completed is as defined as follows: (Excellent: definite pain relief/improvement in signs of bleeding starting within 8 hrs after an infusion, with no additional infusion; Good: definite pain relief/improvement in signs of bleeding starting within 8 hrs or following the infusion; Moderate: probable/slight improvement starting after 8 hours following the infusion; No Response: no improvement at all between infusions). |
| Mean Number of Breakthrough (Spontaneous/Non-traumatic) Bleeds | Baseline to 24 months or early withdrawal. | The number of breakthrough (spontaneous/non-traumatic) bleeds within 48 hours following a prophylaxis dose of Xyntha was summarized. The data from the electronic Infusion Log Diary plus the Test Article CRF was used to determine the number of infusions administered to treat a new bleed, counting only those infusions administered =\<48 hours after an infusion marked as 'prophylaxis' (which had no associated bleed). |
Participant flow
Recruitment details
The study was planned to be conducted in major hemophilia centers in North America, Latin America, and Asia-Pacific regions. Seven (7) sites were initiated; however, recruitment occurred at only 1 site in United State of America (USA) between June 2009 to December 2009. The study was terminated by the Sponsor.
Participants by arm
| Arm | Count |
|---|---|
| Xyntha Participants received intravenous infusion (s) of Xyntha as per dosage and administration frequency as prescribed by the treating physician. | 1 |
| Total | 1 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Termination of the study by sponsor | 1 |
Baseline characteristics
| Characteristic | Xyntha |
|---|---|
| Age, Continuous | 1 Month |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 1 / 1 |
| serious Total, serious adverse events | 1 / 1 |
Outcome results
Primary
Percentage of Participants With Factor VIII (FVIII) Inhibitor Development
Incidence of inhibitor development was defined as any result determined positive at a central laboratory (Bethesda inhibitor titer of \>=0.6 BU/mL) using Nijmegen modification of the Bethesda assay.
Time frame: Baseline to 24 months or early withdrawal.
Population: Intent-to-treat (ITT) population: Participants who had received at least 1 dose of Xyntha.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Xyntha | Percentage of Participants With Factor VIII (FVIII) Inhibitor Development | 0 Percentage of participants |
Primary
Percentage of Participants With Less Than Expected Therapeutic Effects (LETE) in the On-Demand Setting
LETE in the on-demand setting was based on the response to the treatment of a bleeding episode. LETE in the on-demand setting occurred if the participant recorded 2 successive No Response ratings (indicated there was no improvement at all between infusions or during the 24 hour interval following an infusion, or condition worsened) after 2 successive Xyntha infusions, respectively. The infusions was to be administered within 24 hours (=\<24 hours) of each other for the treatment of the same bleeding event in the absence of confounding factor.
Time frame: Baseline to 24 months or early withdrawal.
Population: The study was terminated, analysis was not conducted.
Primary
Percentage of Participants With LETE in the Prophylaxis Setting
The LETE in the prophylaxis setting was the occurrence of a bleed. LETE in the prophylaxis setting occurred if there was a spontaneous bleed within 48 hours (=\<48 hours) after a regularly scheduled prophylactic dose of Xyntha (which was not used to treat a bleed) in the absence of confounding factors.
Time frame: Baseline to 24 months or early withdrawal.
Population: The study was terminated, analysis was not conducted.
Primary
Percentage of Participants With Low Recovery LETE
The LETE could be considered lower than expected recovery of FVIII in the opinion of the investigator following infusion of Xyntha in the absence of confounding factors.
Time frame: Baseline to 24 months or early withdrawal.
Population: The study was terminated, analysis was not conducted.
Secondary
Mean Annualized Bleed Rate (ABR)
An annualized bleeding rate (ABR) for each participant was calculated as the number of bleeds requiring administration of FVIII replacement product (taken from the electronic Infusion Log Diary), divided by his total therapy duration (in days), and then multiplied by 365.25.
Time frame: Baseline to 24 months or early withdrawal.
Population: The study was terminated, analysis was not conducted.
Secondary
Mean Number of Breakthrough (Spontaneous/Non-traumatic) Bleeds
The number of breakthrough (spontaneous/non-traumatic) bleeds within 48 hours following a prophylaxis dose of Xyntha was summarized. The data from the electronic Infusion Log Diary plus the Test Article CRF was used to determine the number of infusions administered to treat a new bleed, counting only those infusions administered =\<48 hours after an infusion marked as 'prophylaxis' (which had no associated bleed).
Time frame: Baseline to 24 months or early withdrawal.
Population: The study was terminated, analysis was not conducted.
Secondary
Number of Xyntha Infusions Needed to Treat Each New Bleed
The data from the electronic Infusion Log Diary plus the Test Article case report form (CRF) was used to determine the number of infusions administered to treat a bleed. This was calculated by adding the initial 'for a new bleed' (on demand) infusion to any subsequent (on demand) infusions for the (same) 'previously treated bleed'. An on-demand infusion for a 'previously treated bleed' was counted toward the bleed with the most recent start time prior to that infusion.
Time frame: Baseline to 24 months or early withdrawal.
Population: The study was terminated, analysis was not conducted.
Secondary
Response to First On-demand Xyntha Treatment for All New Bleeds as Assessed by the Caregiver
A 4-point response scale to be completed is as defined as follows: (Excellent: definite pain relief/improvement in signs of bleeding starting within 8 hrs after an infusion, with no additional infusion; Good: definite pain relief/improvement in signs of bleeding starting within 8 hrs or following the infusion; Moderate: probable/slight improvement starting after 8 hours following the infusion; No Response: no improvement at all between infusions).
Time frame: Baseline to 24 months or early withdrawal
Population: The study was terminated, analysis was not conducted.