Congenital Bleeding Disorder, Haemophilia A
Conditions
Brief summary
This study will test the well-known medicine turoctocog alfa for any side effects. The purpose is to test turoctocog alfa for any side effects in the Indian population. The participants will get turoctocog alfa. Turoctocog alfa is already a well-known medicine in India, and can be prescribed by the study doctor. The participants will get an injection every second day or 3 times per week. This is decided by the study doctor. The study doctor will decide the amount and how often the participants must take the medicine. The study will last for about 16 weeks. The participants will have 5 visits with the study doctor. If the participants agree to participate in this study, the participants will receive the first injection at the second visit, thereafter the participants will be trained to do the injection by themself.
Interventions
DRUGturoctocog alfa
Patients will receive standard prophylaxis treatment and treatment of bleeding episodes, according to label. Trial product will be administered as intravenous injections (i.v.)
Sponsors
Novo Nordisk A/S
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
12 Years to No maximum
Healthy volunteers
No
Inclusion criteria
- Informed consent obtained before any trial-related activities. Trial-related activities are any procedures that are carried out as part of the trial, including activities to determine suitability for the trial - Male, age above or equal to 12 years at the time of signing informed consent - Patients with the diagnosis of congenital moderate or severe Haemophilia A based on medical records. (FVIII below or equal to 5%) - Documented history of at least 150 EDs (exposure days) to FVIII containing products
Exclusion criteria
- Confirmed inhibitors to FVIII (above or equal to 0.6 BU) at screening as assessed by central laboratory - History of FVIII inhibitors - Known or suspected hypersensitivity to trial product(s) or related products - Previous participation in this trial. Participation is defined as signed informed consent - Participation in any clinical trial of an approved or non-approved investigational medicinal product within 1 month before screening (visit 1) - Any disorder, except for conditions associated with haemophilia A, which in the investigator's opinion might jeopardise patient's safety or compliance with the protocol - Immunocompromised patients due to HIV infection (defined as viral load above or equal to 400.000 copies/mL and/or CD4+ lymphocyte count below or equal to 200/μL). HIV status and CD4+ lymphocyte count /viral load results may be obtained at screening or from available medical records; results must be not older than 6 months - Known congenital or acquired coagulation disorders other than haemophilia A - Mental incapacity, unwillingness to cooperate, or a language barrier precluding adequate understanding and cooperation
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Occurrence of Confirmed FVIII Inhibitor Development (≥ 0.6 BU) | Weeks 0-8 | The number of participants who confirmed the presence of FVIII inhibitor development (≥ 0.6 BU) during 8 weeks of treatment period. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Adverse Drug Reactions (ARs) and Serious Adverse Reactions (SARs) | Weeks 0-12 | Incidence of adverse drug reactions (ARs) and serious adverse reactions (SARs) were calculated as the number of adverse reactions per patient years. All presented ARs and SARs are treatment emergent and related to trial product, which were defined as the events reported after trial product administration until the follow-up, 12 weeks after first treatment. |
| Number of Bleeding Episodes With Successful Haemostatic Effect of Turoctocog Alfa | Weeks 0-8 | The haemostatic effect (HE) of turoctocog alfa when used for treatment of bleeding episodes was evaluated during 8 weeks of treatment. Successful haemostatic effect means the haemostatic response when used for treatment of a bleeding episode was either excellent or good. Excellent haemostatic respose: Abrupt pain relief and/or clear improvement in objective signs of bleeding episode within approximately 8 hours after a single injection. Good haemostatic response: Definite pain relief and/or improvement in signs of bleeding episode within approximately 8 hours after an injection, but possibly requiring more than 1 injection for complete resolution. |
| Total Annualised Consumption of Turoctocog Alfa | Weeks 0-8 | Total consumption of turoctocog alfa was evaluated during 8 weeks of treatment and it was presented as IU of turoctocog alfa/kg body weight (BW) per year per participant. |
| Incidence of Allergic or Infusion Reactions Related to the Trial Product | Weeks 0-12 | Incidence of allergic or infusion reactions related to trial products were calculated as the number of reactions per patient years. Allergic reactions are a class of adverse events related to allergy. |
Countries
India
Participant flow
Recruitment details
The trial was conducted at 10 sites in India.
Participants by arm
| Arm | Count |
|---|---|
| Adolescents (12 - <18 Years) Participants were to receive prophylactic (preventive) treatment of turoctocog alfa as intravenous (i.v.) injections at a frequency of 'every second day' or '3 times a week' at a dose in the range of 20-50 IU/kg at the investigator's discretion. Dosing for prophylaxis was according to the approved prescribing information. The total treatment duration for each participant was 8 weeks. Bleeds were treated with one or more turoctocog alfa intravenous (i.v.) bolus injections. The individual dose levels were decided by the investigator based on recommendations from the World Federation of Hemophilia (WFH). Participants who underwent surgery were treated with turoctocog alfa according to WFH recommendations. | 10 |
| Adults (≥18 Years) Participants were to receive prophylactic (preventive) treatment of turoctocog alfa as intravenous (i.v.) injections at a frequency of 'every second day' or '3 times a week' at a dose in the range of 20-50 IU/kg at the investigator's discretion. Dosing for prophylaxis was according to the approved prescribing information. The total treatment duration for each participant was 8 weeks. Bleeds were treated with one or more turoctocog alfa intravenous (i.v.) bolus injections. The individual dose levels were decided by the investigator based on recommendations from the World Federation of Hemophilia (WFH). Participants who underwent surgery were treated with turoctocog alfa according to WFH recommendations. | 50 |
| Total | 60 |
Baseline characteristics
| Characteristic | Adults (≥18 Years) | Total | Adolescents (12 - <18 Years) |
|---|---|---|---|
| Age, Continuous | 27.10 years STANDARD_DEVIATION 7.28 | 24.90 years STANDARD_DEVIATION 8.32 | 13.90 years STANDARD_DEVIATION 1.91 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 50 Participants | 60 Participants | 10 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 50 Participants | 60 Participants | 10 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 50 Participants | 60 Participants | 10 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 10 | 0 / 50 |
| other Total, other adverse events | 2 / 10 | 2 / 50 |
| serious Total, serious adverse events | 0 / 10 | 0 / 50 |
Outcome results
Primary
Occurrence of Confirmed FVIII Inhibitor Development (≥ 0.6 BU)
The number of participants who confirmed the presence of FVIII inhibitor development (≥ 0.6 BU) during 8 weeks of treatment period.
Time frame: Weeks 0-8
Population: Results are based on the full analysis set (FAS), that included all dosed participants with data after dosing during 8 weeks of treatment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Adolescents (12 - <18 Years) | Occurrence of Confirmed FVIII Inhibitor Development (≥ 0.6 BU) | 0 Participants |
| Adults (≥18 Years) | Occurrence of Confirmed FVIII Inhibitor Development (≥ 0.6 BU) | 0 Participants |
Secondary
Incidence of Adverse Drug Reactions (ARs) and Serious Adverse Reactions (SARs)
Incidence of adverse drug reactions (ARs) and serious adverse reactions (SARs) were calculated as the number of adverse reactions per patient years. All presented ARs and SARs are treatment emergent and related to trial product, which were defined as the events reported after trial product administration until the follow-up, 12 weeks after first treatment.
Time frame: Weeks 0-12
Population: Results are based on the safety analysis set (SAS), that included all dosed participants with data after dosing during 8 weeks of treatment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Adolescents (12 - <18 Years) | Incidence of Adverse Drug Reactions (ARs) and Serious Adverse Reactions (SARs) | Adverse drug reaction | 0 Number of ARs per patient years |
| Adolescents (12 - <18 Years) | Incidence of Adverse Drug Reactions (ARs) and Serious Adverse Reactions (SARs) | Serious adverse reactions | 0 Number of ARs per patient years |
| Adults (≥18 Years) | Incidence of Adverse Drug Reactions (ARs) and Serious Adverse Reactions (SARs) | Adverse drug reaction | 0 Number of ARs per patient years |
| Adults (≥18 Years) | Incidence of Adverse Drug Reactions (ARs) and Serious Adverse Reactions (SARs) | Serious adverse reactions | 0 Number of ARs per patient years |
Secondary
Incidence of Allergic or Infusion Reactions Related to the Trial Product
Incidence of allergic or infusion reactions related to trial products were calculated as the number of reactions per patient years. Allergic reactions are a class of adverse events related to allergy.
Time frame: Weeks 0-12
Population: Results are based on the SAS, that included all dosed participants with data after dosing during 8 weeks of treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Adolescents (12 - <18 Years) | Incidence of Allergic or Infusion Reactions Related to the Trial Product | 0 Number of reactions per patient years |
| Adults (≥18 Years) | Incidence of Allergic or Infusion Reactions Related to the Trial Product | 0 Number of reactions per patient years |
Secondary
Number of Bleeding Episodes With Successful Haemostatic Effect of Turoctocog Alfa
The haemostatic effect (HE) of turoctocog alfa when used for treatment of bleeding episodes was evaluated during 8 weeks of treatment. Successful haemostatic effect means the haemostatic response when used for treatment of a bleeding episode was either excellent or good. Excellent haemostatic respose: Abrupt pain relief and/or clear improvement in objective signs of bleeding episode within approximately 8 hours after a single injection. Good haemostatic response: Definite pain relief and/or improvement in signs of bleeding episode within approximately 8 hours after an injection, but possibly requiring more than 1 injection for complete resolution.
Time frame: Weeks 0-8
Population: Results are based on the FAS that included all dosed participants with data after dosing during 8 weeks of treatment. Overall Number of Participants Analyzed = Number of participants with bleeding episodes treated with turoctocog alfa.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Adolescents (12 - <18 Years) | Number of Bleeding Episodes With Successful Haemostatic Effect of Turoctocog Alfa | 2 Bleeding episodes with successfull HE |
| Adults (≥18 Years) | Number of Bleeding Episodes With Successful Haemostatic Effect of Turoctocog Alfa | 38 Bleeding episodes with successfull HE |
Secondary
Total Annualised Consumption of Turoctocog Alfa
Total consumption of turoctocog alfa was evaluated during 8 weeks of treatment and it was presented as IU of turoctocog alfa/kg body weight (BW) per year per participant.
Time frame: Weeks 0-8
Population: Results are based on the FAS that included all dosed participants with data after dosing during 8 weeks of treatment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Adolescents (12 - <18 Years) | Total Annualised Consumption of Turoctocog Alfa | 7030 IU/kg BW/year/participant | Standard Deviation 1053 |
| Adults (≥18 Years) | Total Annualised Consumption of Turoctocog Alfa | 6086 IU/kg BW/year/participant | Standard Deviation 1735 |