Severe Hemophilia A
Conditions
Keywords
Previously untreated patients
Brief summary
Investigate 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
* Male patients * Severe Hemophilia A (FVIII:C \<1%) * No previous treatment with FVIII concentrates or other blood products containing FVIII
Exclusion criteria
* Diagnosis with a coagulation disorder other than Hemophilia A * Severe liver or kidney disease * Concomitant treatment with any systemic immunosuppressive drug
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Immunogenicity of Human-cl rhFVIII: Incidence of Inhibitors | maximum 5 years (100 exposure days) | The number of patients developing FVIII inhibitors was observed during the observation period by assessing inhibitor development using the modified Bethesda assay (Nijmegen modification). The definitions for thresholds were ≥0.6 to \<5 BU/mL for a low titre inhibitor and ≥5 BU/mL for a high-titre inhibitor. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Frequency of Spontaneous Break-through Bleeds | Maximum 5 years (100 exposure days) | The annualized bleeding rate (ABR) was calculated during inhibitor-free periods for spontaneous bleeding events (BEs) during prophylactic treatment with Human cl rhFVIII |
| Efficacy of Human-cl rhFVIII for the Treatment of Bleeds | Maximum 5 years (100 exposure days) | A personal efficacy assessment to assess the efficacy of Human-cl rhFVIII for the on-demand treatment of bleeding episodes. Efficacy was assessed using a four-point scale (excellent, good, moderate, none). |
| Efficacy of Human-cl rhFVIII for Surgical Prophylaxis | Maximum 5 years (100 exposure days) | 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). |
Other
| Measure | Time frame | Description |
|---|---|---|
| The Occurrence of Any Adverse Event (AE) | 5 years | The frequency of AEs, as monitored throughout the whole study by the number of patients with at least one adverse event occurrence. |
Countries
Belarus, Canada, France, Georgia, Germany, India, Italy, Moldova, Morocco, Poland, Portugal, Russia, Slovenia, Spain, Ukraine, United Kingdom, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Human-cl rhFVIII The safety (SAF) and intent-to-treat (ITT) population consists all patients who had data collected post-treatment with Human-cl rhFVIII (n=108). | 108 |
| Total | 108 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Not treated with Human-cl rhFVIII | 2 |
| Overall Study | Ongoing ITI treatment | 6 |
| Overall Study | Prematurely Discontinued | 25 |
| Overall Study | Violated inclusion & exclusion criteria | 4 |
Baseline characteristics
| Characteristic | Human-cl rhFVIII |
|---|---|
| Age, Continuous | 19.0 months |
| Body Mass Index (BMI) at Exposure Day 1 (ED1) | 17.2 kg/m2 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 105 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Family history of inhibitors No | 95 Participants |
| Family history of inhibitors Yes | 13 Participants |
| Height at Exposure Day 1 (ED1) | 82.0 centimeters (cm) |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants |
| Race (NIH/OMB) Asian | 14 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 4 Participants |
| Race (NIH/OMB) White | 89 Participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 108 Participants |
| Weight at Exposure Day 1 (ED1) | 11.7 kilograms (kg) |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 108 |
| other Total, other adverse events | 101 / 108 |
| serious Total, serious adverse events | 48 / 108 |
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 using the modified Bethesda assay (Nijmegen modification). The definitions for thresholds were ≥0.6 to \<5 BU/mL for a low titre inhibitor and ≥5 BU/mL for a high-titre inhibitor.
Time frame: maximum 5 years (100 exposure days)
Population: The analysis was performed for the SAF/ITT population which includes all patients who had data collected post-treatment with Human-cl rhFVIII (n=108). Of the 108 patients, 105 patients had at least one inhibitor test after exposure day (ED) 1.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| SAF/ITT Population | Immunogenicity of Human-cl rhFVIII: Incidence of Inhibitors | High titre inhibitor (>5 BU/mL) | 17 Participants |
| SAF/ITT Population | Immunogenicity of Human-cl rhFVIII: Incidence of Inhibitors | Low titre inhibitor (<5 BU/mL) | 11 Participants |
| SAF/ITT Population | Immunogenicity of Human-cl rhFVIII: Incidence of Inhibitors | Any inhibitor (>0.6 BU/mL) | 28 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).
Time frame: Maximum 5 years (100 exposure days)
Population: The analysis population includes 24 patients that received Human-cl rhFVIII for surgical prophylaxis during a total of 26 surgeries (SURG population). Of these, 13 patients had minor surgeries and 11 patients had major surgeries. Of the total 26 surgeries, 21 had an overall efficacy assessment (an assessment was not performed for 5 surgeries).
| Arm | Measure | Category | Value (COUNT_OF_UNITS) |
|---|---|---|---|
| SAF/ITT Population | Efficacy of Human-cl rhFVIII for Surgical Prophylaxis | Good | 1 Number of surgeries |
| SAF/ITT Population | Efficacy of Human-cl rhFVIII for Surgical Prophylaxis | Moderate | 1 Number of surgeries |
| SAF/ITT Population | Efficacy of Human-cl rhFVIII for Surgical Prophylaxis | Excellent | 7 Number of surgeries |
| SAF/ITT Population | Efficacy of Human-cl rhFVIII for Surgical Prophylaxis | None | 1 Number of surgeries |
| Major Surgeries | Efficacy of Human-cl rhFVIII for Surgical Prophylaxis | Good | 2 Number of surgeries |
| Major Surgeries | Efficacy of Human-cl rhFVIII for Surgical Prophylaxis | Excellent | 8 Number of surgeries |
| Major Surgeries | Efficacy of Human-cl rhFVIII for Surgical Prophylaxis | Moderate | 1 Number of surgeries |
| Major Surgeries | Efficacy of Human-cl rhFVIII for Surgical Prophylaxis | None | 0 Number of surgeries |
| All Surgeries | Efficacy of Human-cl rhFVIII for Surgical Prophylaxis | Moderate | 2 Number of surgeries |
| All Surgeries | Efficacy of Human-cl rhFVIII for Surgical Prophylaxis | Excellent | 15 Number of surgeries |
| All Surgeries | Efficacy of Human-cl rhFVIII for Surgical Prophylaxis | Good | 3 Number of surgeries |
| All Surgeries | Efficacy of Human-cl rhFVIII for Surgical Prophylaxis | None | 1 Number of surgeries |
Secondary
Efficacy of Human-cl rhFVIII for the Treatment of Bleeds
A personal efficacy assessment to assess the efficacy of Human-cl rhFVIII for the on-demand treatment of bleeding episodes. Efficacy was assessed using a four-point scale (excellent, good, moderate, none).
Time frame: Maximum 5 years (100 exposure days)
Population: The analysis population includes patients (n=94) who received Human-cl rhFVIII for on-demand treatment of BEs (BLEED population).
| Arm | Measure | Group | Value (COUNT_OF_UNITS) |
|---|---|---|---|
| SAF/ITT Population | Efficacy of Human-cl rhFVIII for the Treatment of Bleeds | Excellent | 510 Number of Bleeding Events |
| SAF/ITT Population | Efficacy of Human-cl rhFVIII for the Treatment of Bleeds | Good | 237 Number of Bleeding Events |
| SAF/ITT Population | Efficacy of Human-cl rhFVIII for the Treatment of Bleeds | Moderate | 51 Number of Bleeding Events |
| SAF/ITT Population | Efficacy of Human-cl rhFVIII for the Treatment of Bleeds | None | 6 Number of Bleeding Events |
Secondary
Frequency of Spontaneous Break-through Bleeds
The annualized bleeding rate (ABR) was calculated during inhibitor-free periods for spontaneous bleeding events (BEs) during prophylactic treatment with Human cl rhFVIII
Time frame: Maximum 5 years (100 exposure days)
Population: The analysis population includes all patients who received at least one prophylactic treatment with Human-cl rhFVIII (PROPH population; n=103). Of all patients in the PROPH population, data was available on spontaneous break-through bleeds for 102 patients.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| SAF/ITT Population | Frequency of Spontaneous Break-through Bleeds | 0.976 No. BEs per duration (year) (ABR) |
Other Pre-specified
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: 5 years
Population: Of the 110 patients enrolled in the study, 2 were excluded because they had no treatment with Human-cl rhFVIII leaving 108 patients in the safety (SAF) and intent-to-treat (ITT) population.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| SAF/ITT Population | The Occurrence of Any Adverse Event (AE) | Severe AE | 27 Participants |
| SAF/ITT Population | The Occurrence of Any Adverse Event (AE) | Adverse Event (AE) | 101 Participants |
| SAF/ITT Population | The Occurrence of Any Adverse Event (AE) | Serious adverse event (SAE) | 48 Participants |
| SAF/ITT Population | The Occurrence of Any Adverse Event (AE) | Temporally related adverse event | 78 Participants |
| SAF/ITT Population | The Occurrence of Any Adverse Event (AE) | Death | 0 Participants |
| SAF/ITT Population | The Occurrence of Any Adverse Event (AE) | Death due to probably/possibly related AE | 0 Participants |
| SAF/ITT Population | The Occurrence of Any Adverse Event (AE) | AE leading to permanent study discontinuation | 2 Participants |