Hematologic Disease, Hemophilia A
Conditions
Keywords
Coagulation Disorders
Brief summary
The purpose of the study is to evaluate the effect of prophylactic treatment on the number of joint bleeds and quality of life in severe hemophilia A subjects compared to on-demand treatment in a one-group two-treatment schedule design. In addition, the effect of prophylactic treatment on the joint function, the number of all bleeds, and on the quality of life compared to on-demand treatment and health-economic data will be assessed.
Interventions
One group two treatment schedules, first on-demand then switch to prophylaxis
Sponsors
Bayer
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
30 Years to 45 Years
Healthy volunteers
No
Inclusion criteria
* Severe hemophilia A (\< 1% FVIII) * 30-45 years of age * Previously treated subject (\> 100 Exposure days to any FVIII) * On-demand therapy with any FVIII
Exclusion criteria
* No history of inhibitor * No planned elective orthopedic surgery during the study duration (13 months) * No severe concomitant disease * No history of anaphylactic or other severe reaction to previous FVIII treatment
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Joint Bleeds | Months 1-6 (on-demand treatment) and 8-13 (prophylactic treatment) | Number of joint bleeds during Months 8-13 compared to number of joint bleeds during Months 1-6 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of All Bleeds | Months 1-6 (on-demand treatment) and 8-13 (prophylactic treatment) | Mean number of all bleeds during Months 8-13 (prophylactic) compared to mean number of all bleeds during Months 1-6 (on-demand) |
| Physical Assessment Compared to On-demand Treatment as Determined by the Gilbert Score | Month 13 (end of prophylactic treatment) and Month 6 (end of on-demand treatment) | Total score with a range of 0-100, evaluating ankle, knee and elbow, 0 indicates normal function, higher values indicate joint damage |
| Quality of Life Compared to On-demand Treatment as Measured by the Haemo-QoL A Questionnaire | Month 13 (end of prophylactic treatment) and Month 6 (end of on-demand treatment) | Total transformed score with a range of 0-100, higher values indicate better outcome. 41 items in 6 domains: physical functioning; role functioning; worry; consequences; positive affect; treatment concern. |
Countries
France, Italy, Spain, United Kingdom, United States
Participant flow
Recruitment details
Patients were recruited at Haemophilia treatment centers
Pre-assignment details
All subjects who met eligibility criteria on screening were enrolled into the study and began the on-demand treatment period.
Participants by arm
| Arm | Count |
|---|---|
| rFVIII-FS (Octocog-alfa), (Kogenate FS) On-demand treatment was to follow the same treatment pattern the subject was using before entering the study. While on prophylactic treatment, all subjects were to be treated at a dose of 20-40 IU/kg, 3 times per week at a stable dose. | 20 |
| Total | 20 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| On Demand Treatment (Months 1-6) | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | rFVIII-FS (Octocog-alfa), (Kogenate FS) |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 20 Participants |
| Age, Continuous | 36.4 years STANDARD_DEVIATION 3.5 |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 20 Participants |
| Target joints presence Number participants without target joints presence | 4 participants |
| Target joints presence Number participants with target joints presence | 16 participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 12 / 20 |
| serious Total, serious adverse events | 2 / 20 |
Outcome results
Primary
Number of Joint Bleeds
Number of joint bleeds during Months 8-13 compared to number of joint bleeds during Months 1-6
Time frame: Months 1-6 (on-demand treatment) and 8-13 (prophylactic treatment)
Population: intent-to-treat population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| rFVIII-FS (Octocog-alfa), (Kogenate FS) | Number of Joint Bleeds | Months 1-6 (on-demand) | 18.5 Number of joint bleeds | Standard Deviation 11.6 |
| rFVIII-FS (Octocog-alfa), (Kogenate FS) | Number of Joint Bleeds | Months 8-13 (prophylactic) | 1.5 Number of joint bleeds | Standard Deviation 2.1 |
Comparison: The primary outcome measure was analyzed by paired t-test and Wilcoxon test (number of joint bleeds prophylaxis treatment compared to number of joint bleeds on-demand treatment) at 6 months of treatment.p-value: <0.001Wilcoxon (Mann-Whitney)
Comparison: The maximum individual reduction in the actual number of joint bleeds after the switch to prophylactic treatment was analyzed by a paired t-test of the individual difference between prophylaxis treatment bleed compared to on-demand treatment bleeds.p-value: <0.001paired t-test
Secondary
Number of All Bleeds
Mean number of all bleeds during Months 8-13 (prophylactic) compared to mean number of all bleeds during Months 1-6 (on-demand)
Time frame: Months 1-6 (on-demand treatment) and 8-13 (prophylactic treatment)
Population: intention-to-treat
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| rFVIII-FS (Octocog-alfa), (Kogenate FS) | Number of All Bleeds | Month 8-13 (prophylactic) | 1.9 All bleeds | Standard Deviation 3.3 |
| rFVIII-FS (Octocog-alfa), (Kogenate FS) | Number of All Bleeds | Months 1-6 (on-demand) | 23.7 All bleeds | Standard Deviation 13.3 |
Comparison: paired t-test (prophylaxis compared to on-demand) at 6 months of treatment.p-value: <0.001paired t-test
Secondary
Physical Assessment Compared to On-demand Treatment as Determined by the Gilbert Score
Total score with a range of 0-100, evaluating ankle, knee and elbow, 0 indicates normal function, higher values indicate joint damage
Time frame: Month 13 (end of prophylactic treatment) and Month 6 (end of on-demand treatment)
Population: intent-to-treat
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| rFVIII-FS (Octocog-alfa), (Kogenate FS) | Physical Assessment Compared to On-demand Treatment as Determined by the Gilbert Score | Month 6 (on-demand) | 25.3 Gilbert score (0-100) | Standard Deviation 11.7 |
| rFVIII-FS (Octocog-alfa), (Kogenate FS) | Physical Assessment Compared to On-demand Treatment as Determined by the Gilbert Score | Month 13 (prophylactic) | 19.8 Gilbert score (0-100) | Standard Deviation 11.7 |
Comparison: The Gilbert Score was the sum of 3 scores: pain (0=no pain to 3=severe pain); bleeding score (0=none to 3=3 or more major bleeds or 7 or more minor bleeds); and physical score (based on swelling, muscle atrophy; and axial deformity (at knee or ankle), range of motion, crepitus on motion, flexion contracture, instability.p-value: <0.001paired t-test
Secondary
Quality of Life Compared to On-demand Treatment as Measured by the Haemo-QoL A Questionnaire
Total transformed score with a range of 0-100, higher values indicate better outcome. 41 items in 6 domains: physical functioning; role functioning; worry; consequences; positive affect; treatment concern.
Time frame: Month 13 (end of prophylactic treatment) and Month 6 (end of on-demand treatment)
Population: intent-to-treat-population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| rFVIII-FS (Octocog-alfa), (Kogenate FS) | Quality of Life Compared to On-demand Treatment as Measured by the Haemo-QoL A Questionnaire | Month 6 (on-demand) | 73.4 Transformed score | Standard Deviation 17.4 |
| rFVIII-FS (Octocog-alfa), (Kogenate FS) | Quality of Life Compared to On-demand Treatment as Measured by the Haemo-QoL A Questionnaire | Month 13 (prophylactic) | 75.9 Transformed score | Standard Deviation 16.1 |
Comparison: The Haemo-QoL A questionnaire measures the subject's self-assessment of disease impact on physical functioning, role functioning, worry, consequences, positive affect, and treatment concern.p-value: 0.314paired t-test