Severe Hemophilia A
Conditions
Brief summary
The purpose of the study is to study the long-term efficacy, safety and tolerability of Human-cl rhFVIII in previously treated patients with severe hemophilia A.
Interventions
BIOLOGICALHuman-cl rhFVIII
Human-cl rhFVIII is administered intravenously on demand for bleeding episodes and prophylactically in case of surgery. The dosage depends on the severity of the bleeding episodes and the surgery.
Sponsors
Octapharma
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
12 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Completion of GENA-01 study with at least 50 Exposure Days (EDs) and at least 6 months study participation and immediate enrollment into GENA-11
Exclusion criteria
* Development of FVIII inhibitors (\<=0.6 BU), during the course of the GENA-01 study * Development of any severe liver or kidney disease (ALT and AST level \> 5 times of upper limit of normal, creatine \>120 micro mol/L) during the course of the GENA-01 study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Long-term Immunogenicity | up to 3 years | Patients will be monitored for inhibitors against FVIII every 3 months. Blood samples were drawn and inhibitor activity was determined by the modified Bethesda assay (Nijmegen modification) in the central lab. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| To Determine Long-term Efficacy of Human-cl rhFVIII in the Treatment of Bleeding Episodes and in Surgical Prophylaxis | up to 3 years | The efficacy of human-cl rhFVIII will be determined using a 4 point efficacy assessment scale. After each infusion of IMP and at the end of a BE, the following efficacy assessment is made by the subject (together with the Investigator in case of on-site treatment): Excellent: Abrupt pain relief and/or unequivocal improvement in objective signs of bleeding within approximately 8 hours after a single infusion. Good: Definite pain relief and/or improvement in signs of bleeding within approximately 8 - 12 hours after an infusion requiring up to 2 infusions for complete resolution. Moderate: Probable or slight beneficial effect within approximately 12 hours after the first infusion requiring more than two infusions for complete resolution. None: No improvement within 12 hours, or worsening of symptoms, requiring more than 2 infusions for complete resolution. The assessment was made at the end of a BE in case more than one infusion was needed. |
Countries
Bulgaria, United States
Participant flow
Recruitment details
This study was open to all patients who had completed the GENA-01 study with at least 50 exposure days after at least 6 months of study participation (EU patients) or at least 15 months of study participation (US patients). Overall 21 patients were eligible for this study but only 3 patients decided to participate in this extension study.
Participants by arm
| Arm | Count |
|---|---|
| Human-cl rhFVIII Recombinant FVIII derived from a human cell line.
Human-cl rhFVIII : Human-cl rhFVIII is administered intravenously on demand for bleeding episodes and prophylactically in case of surgery. The dosage depends on the severity of the bleeding episodes and the surgery. | 3 |
| Total | 3 |
Baseline characteristics
| Characteristic | Human-cl rhFVIII |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 1 Participants |
| Age, Categorical Between 18 and 65 years | 2 Participants |
| Age, Continuous | 52 years STANDARD_DEVIATION 12.29 |
| Region of Enrollment Bulgaria | 3 participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 0 / 3 |
| serious Total, serious adverse events | 0 / 3 |
Outcome results
Primary
Long-term Immunogenicity
Patients will be monitored for inhibitors against FVIII every 3 months. Blood samples were drawn and inhibitor activity was determined by the modified Bethesda assay (Nijmegen modification) in the central lab.
Time frame: up to 3 years
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Human-cl rhFVIII | Long-term Immunogenicity | 0 occurrence of inhibitors |
Secondary
To Determine Long-term Efficacy of Human-cl rhFVIII in the Treatment of Bleeding Episodes and in Surgical Prophylaxis
The efficacy of human-cl rhFVIII will be determined using a 4 point efficacy assessment scale. After each infusion of IMP and at the end of a BE, the following efficacy assessment is made by the subject (together with the Investigator in case of on-site treatment): Excellent: Abrupt pain relief and/or unequivocal improvement in objective signs of bleeding within approximately 8 hours after a single infusion. Good: Definite pain relief and/or improvement in signs of bleeding within approximately 8 - 12 hours after an infusion requiring up to 2 infusions for complete resolution. Moderate: Probable or slight beneficial effect within approximately 12 hours after the first infusion requiring more than two infusions for complete resolution. None: No improvement within 12 hours, or worsening of symptoms, requiring more than 2 infusions for complete resolution. The assessment was made at the end of a BE in case more than one infusion was needed.
Time frame: up to 3 years
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Human-cl rhFVIII | To Determine Long-term Efficacy of Human-cl rhFVIII in the Treatment of Bleeding Episodes and in Surgical Prophylaxis | Excellent | 71.88 percentage of bleeding episodes |
| Human-cl rhFVIII | To Determine Long-term Efficacy of Human-cl rhFVIII in the Treatment of Bleeding Episodes and in Surgical Prophylaxis | Good | 26.56 percentage of bleeding episodes |
| Human-cl rhFVIII | To Determine Long-term Efficacy of Human-cl rhFVIII in the Treatment of Bleeding Episodes and in Surgical Prophylaxis | Moderate | 1.56 percentage of bleeding episodes |
| Human-cl rhFVIII | To Determine Long-term Efficacy of Human-cl rhFVIII in the Treatment of Bleeding Episodes and in Surgical Prophylaxis | None | 0 percentage of bleeding episodes |