Severe Hemophilia A
Conditions
Brief summary
The purpose of the study is to collect long-term data on the inhibitor development rate of Human-cl rhFVIII in previously untreated patients with severe Hemophilia A.
Interventions
BIOLOGICALHuman-cl rhFVIII
Sponsors
Octapharma
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Healthy volunteers
No
Inclusion criteria
1\. Patients who completed GENA-05 in accordance with the study protocol
Exclusion criteria
1. Severe liver or kidney disease 2. Concomitant treatment with any systemic immunosuppressive drug; 3. Other FVIII concentrate than Human-cl rhFVIII was received between completion visit of GENA-05 and start of GENA-15 (except emergency cases).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Immunogenicity of Human-cl rhFVIII: Incidence of Inhibitors | Maximum two years | The number of patients developing FVIII inhibitors was observed during the observation period by assessing inhibitor development by the modified Bethesda assay (Nijmegen modification) using congenital FVIII-deficient human plasma spiked with Human-cl rhFVIII. The definition threshold for a positive inhibitor was if the modified Bethesda assay resulted in a titre ≥0.6 BU/mL at any time point during the observation period. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Frequency of Spontaneous Break-through Bleeds | Maximum 2 years | The annualized bleeding rate (ABR) was calculated during the time of prophylactic treatment with Human-cl rhFVIII for spontaneous bleeding events (BEs). |
| Efficacy of Human-cl rhFVIII for the Treatment of Bleeds | Maximum 2 years | A personal efficacy assessment (final outcome) to assess the efficacy of Human-cl rhFVIII for the on-demand treatment of bleeding episodes (BEs) at the end of a BE. Efficacy was assessed using a four-point scale (excellent, good, moderate, none) by the patient's parent(s)/legal guardian(s) together with the investigator in case of on site treatment. |
| Efficacy of Human-cl rhFVIII for Surgical Prophylaxis | Maximum 2 years | An overall efficacy assessment to assess the efficacy of human-cl rhFVIII in surgical prophylaxis of minor and major surgeries. The efficacy assessment was analyzed using a four-point scale (excellent, good, moderate, none). If surgeries could not be assessed due to limited data available or having taken place outside the study site, the results were classified as not done. |
| The Occurrence of Any Adverse Event (AE) | Maximum 2 years | The frequency of AEs, as monitored throughout the whole study by the number of patients with at least one adverse event occurrence. |
Countries
Canada, France, Georgia, India, Moldova, Poland, Ukraine, United Kingdom, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Human-cl rhFVIII The safety (SAF) population consist of all patients who received at least one infusion of Human-cl rhFVIII (n=48). | 48 |
| Total | 48 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Lost to Follow-up | 2 |
| Overall Study | Product Switch to Extend Half Life | 1 |
| Overall Study | Serious Adverse Event | 1 |
Baseline characteristics
| Characteristic | Human-cl rhFVIII |
|---|---|
| Age, Continuous | 3.47 Years STANDARD_DEVIATION 2.13 |
| Body Mass Index (BMI) at screening | 16.46 kg/m^2 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 48 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Family history of inhibitors No | 45 Participants |
| Family history of inhibitors Yes | 3 Participants |
| Height at screening | 97.44 Centimeters (cm) |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants |
| Race (NIH/OMB) Asian | 9 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 2 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 36 Participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 48 Participants |
| Weight at screening | 15.84 Kilograms (kg) |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 48 |
| other Total, other adverse events | 29 / 48 |
| serious Total, serious adverse events | 5 / 48 |
Outcome results
Primary
Immunogenicity of Human-cl rhFVIII: Incidence of Inhibitors
The number of patients developing FVIII inhibitors was observed during the observation period by assessing inhibitor development by the modified Bethesda assay (Nijmegen modification) using congenital FVIII-deficient human plasma spiked with Human-cl rhFVIII. The definition threshold for a positive inhibitor was if the modified Bethesda assay resulted in a titre ≥0.6 BU/mL at any time point during the observation period.
Time frame: Maximum two years
Population: The analysis was performed for the safety (SAF) population which includes all patients who received at least 1 infusion of Human-cl rhFVIII (N=48)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Human-cl rhFVIII | Immunogenicity of Human-cl rhFVIII: Incidence of Inhibitors | 0 participants |
Secondary
Efficacy of Human-cl rhFVIII for Surgical Prophylaxis
An overall efficacy assessment to assess the efficacy of human-cl rhFVIII in surgical prophylaxis of minor and major surgeries. The efficacy assessment was analyzed using a four-point scale (excellent, good, moderate, none). If surgeries could not be assessed due to limited data available or having taken place outside the study site, the results were classified as not done.
Time frame: Maximum 2 years
Population: The analysis population includes 3 patients that received Human-cl rhFVIII for surgical prophylaxis during a total of 4 surgeries (SURG population). Of these, 1 patient had two minor surgeries and 2 patients had one major surgery each.
| Arm | Measure | Category | Value (COUNT_OF_UNITS) |
|---|---|---|---|
| Human-cl rhFVIII | Efficacy of Human-cl rhFVIII for Surgical Prophylaxis | None | 0 Surgeries |
| Human-cl rhFVIII | Efficacy of Human-cl rhFVIII for Surgical Prophylaxis | Moderate | 0 Surgeries |
| Human-cl rhFVIII | Efficacy of Human-cl rhFVIII for Surgical Prophylaxis | Excellent | 0 Surgeries |
| Human-cl rhFVIII | Efficacy of Human-cl rhFVIII for Surgical Prophylaxis | Good | 0 Surgeries |
| Human-cl rhFVIII | Efficacy of Human-cl rhFVIII for Surgical Prophylaxis | Not done | 2 Surgeries |
| Major Surgeries | Efficacy of Human-cl rhFVIII for Surgical Prophylaxis | Moderate | 0 Surgeries |
| Major Surgeries | Efficacy of Human-cl rhFVIII for Surgical Prophylaxis | Excellent | 2 Surgeries |
| Major Surgeries | Efficacy of Human-cl rhFVIII for Surgical Prophylaxis | Good | 0 Surgeries |
| Major Surgeries | Efficacy of Human-cl rhFVIII for Surgical Prophylaxis | None | 0 Surgeries |
| Major Surgeries | Efficacy of Human-cl rhFVIII for Surgical Prophylaxis | Not done | 0 Surgeries |
| SURG Population | Efficacy of Human-cl rhFVIII for Surgical Prophylaxis | Not done | 2 Surgeries |
| SURG Population | Efficacy of Human-cl rhFVIII for Surgical Prophylaxis | None | 0 Surgeries |
| SURG Population | Efficacy of Human-cl rhFVIII for Surgical Prophylaxis | Excellent | 2 Surgeries |
| SURG Population | Efficacy of Human-cl rhFVIII for Surgical Prophylaxis | Moderate | 0 Surgeries |
| SURG Population | Efficacy of Human-cl rhFVIII for Surgical Prophylaxis | Good | 0 Surgeries |
Secondary
Efficacy of Human-cl rhFVIII for the Treatment of Bleeds
A personal efficacy assessment (final outcome) to assess the efficacy of Human-cl rhFVIII for the on-demand treatment of bleeding episodes (BEs) at the end of a BE. Efficacy was assessed using a four-point scale (excellent, good, moderate, none) by the patient's parent(s)/legal guardian(s) together with the investigator in case of on site treatment.
Time frame: Maximum 2 years
Population: The analysis population included all patients who received on-demand treatment with Human-cl rhFVIII for bleeding episodes (BLEED population; n=29).
| Arm | Measure | Category | Value (COUNT_OF_UNITS) |
|---|---|---|---|
| Human-cl rhFVIII | Efficacy of Human-cl rhFVIII for the Treatment of Bleeds | Excellent | 58 Bleeding episodes |
| Human-cl rhFVIII | Efficacy of Human-cl rhFVIII for the Treatment of Bleeds | Good | 28 Bleeding episodes |
| Human-cl rhFVIII | Efficacy of Human-cl rhFVIII for the Treatment of Bleeds | Moderate | 21 Bleeding episodes |
| Human-cl rhFVIII | Efficacy of Human-cl rhFVIII for the Treatment of Bleeds | None | 3 Bleeding episodes |
| Human-cl rhFVIII | Efficacy of Human-cl rhFVIII for the Treatment of Bleeds | Not done | 1 Bleeding episodes |
Secondary
Frequency of Spontaneous Break-through Bleeds
The annualized bleeding rate (ABR) was calculated during the time of prophylactic treatment with Human-cl rhFVIII for spontaneous bleeding events (BEs).
Time frame: Maximum 2 years
Population: The analysis population includes all patients in PROPH population who received at least one prophylactic treatment with Human-cl rhFVIII (n=47).
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Human-cl rhFVIII | Frequency of Spontaneous Break-through Bleeds | 0.283 Events/year (ABR) |
Secondary
The Occurrence of Any Adverse Event (AE)
The frequency of AEs, as monitored throughout the whole study by the number of patients with at least one adverse event occurrence.
Time frame: Maximum 2 years
Population: The analysis was performed for the safety (SAF) population which includes all patients who received at least 1 infusion of Human-cl rhFVIII (n=48).
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Human-cl rhFVIII | The Occurrence of Any Adverse Event (AE) | Serious adverse event (SAE) | 5 Participants |
| Human-cl rhFVIII | The Occurrence of Any Adverse Event (AE) | Adverse event | 29 Participants |
| Human-cl rhFVIII | The Occurrence of Any Adverse Event (AE) | Severe AE | 3 Participants |
| Human-cl rhFVIII | The Occurrence of Any Adverse Event (AE) | Temporally related adverse event | 20 Participants |
| Human-cl rhFVIII | The Occurrence of Any Adverse Event (AE) | Death | 0 Participants |
| Human-cl rhFVIII | The Occurrence of Any Adverse Event (AE) | AE leading to permanent discontinuation | 1 Participants |