Congenital Bleeding Disorder, Haemophilia B
Conditions
Brief summary
This trial is conducted in Africa, Asia, Europe and the United States of America (USA). The aim of the trial is to evaluate the safety and efficacy of NNC-0156-0000-0009 (nonacog beta pegol) during surgical procedures in patients with haemophilia B.
Interventions
The patients will receive nonacog beta pegol at screening just prior to and during surgical intervention, administered intravenously (into the vein).
Sponsors
Novo Nordisk A/S
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
13 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* Patients with haemophilia B with a FIX activity below or equal to 2% * Male patients with moderately severe or severe congenital haemophilia B with a FIX activity below or equal to 2% according to medical records * History of at least 150 exposure days to other FIX products * Scheduled major surgery
Exclusion criteria
* Known history of FIX (coagulation factor nine) inhibitors based on existing medical records, laboratory report reviews and patient and LAR (legal acceptable representative) interviews * Current FIX (coagulation factor nine) inhibitors above or equal to 0.6 Bethesda Units (central laboratory) * Previous arterial thrombotic events (e.g. myocardial infarction and intracranial thrombosis) or previous deep venous thrombosis or pulmonary embolism (as defined by available medical records) * ALT (alanine aminotransferase) 3 times the upper limit of normal reference ranges at screening (central laboratory) * Immune modulating or chemotherapeutic medication
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Haemostatic Effect During Surgery Evaluated by the Four-point Response Scale (Excellent, Good, Moderate, Poor) | At the day of surgery | Haemostatic effect during surgery was evaluated immediately after surgery (last stitch) using a fourpoint response scale: \- Four-point response scale: Excellent, good, moderate, poor. The evaluation was done by the surgeon, anaesthesiologist and/or investigator based on experience as follows: 1. Excellent: Better than expected/predicted in this type of procedure. 2. Good: As expected in this type of procedure. 3. Moderate: Less than optimal for the type of procedure but haemostatic response maintained without change of treatment regimen. 4. Poor: Bleeding due to inadequate therapeutic response with adequate dosing, change of regimen required. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Transfusion Requirements (Fulfilling Transfusion Criteria) | during surgery (the time from knife to skin until last stitch) and post-operative period (day 1 to day 13) | Mean quantity of transfusion during surgery (the time from knife to skin until last stitch) and the postoperative period (Day 1-13).None of the patients required transfusions beyond Day 6 hence no values presented for days 7-13. |
| Haemoglobin Pre- and Post-surgery Start | 0, 1 hour, 24 hours. | The mean pre-surgery and post surgery haemoglobin level. |
| Consumption of NNC-0156-0000-0009 (U/kg Body Weight) | During surgery (the time from knife to skin until last stitch) and post-operative period (day 1 to day 13) | Mean consumption of nonacog beta pegol (U/kg) used for treatment per patient before surgery, during surgery (the time from knife to skin until last stitch) and post-operative period. |
| Incidence of Serious Adverse Events (SAE) | During the trial period (2-8 weeks prior to day of surgery (transferred subjects) or 2-4 weeks prior to day of surgery (new subjects) until 4 weeks after post-operative period (day 1 to day 13) | The number of serious adverse events per patient years of exposure, reported during the trial period. Number is the only available option here, the data presented are rate of AEs. |
| Incidence of Inhibitors Against FIX (Coagulation Factor Nine) | During the trial period (2-8 weeks prior to day of surgery (transferred subjects) or 2-4 weeks prior to day of surgery (new subjects) and every 4 weeks after post-operative period (day 1 to day 13) | Number of patients with inhibitory antibodies |
| Incidence of Adverse Events (AEs) | during the trial period (2-8 weeks prior to day of surgery (transferred subjects) or 2-4 weeks prior to day of surgery (new subjects) until 4 weeks after post-operative period (day 1 to day 13) | The number of adverse events per patient years of exposure, reported during the trial period. Number is the only available option here, the data presented are rate of AEs. |
Countries
Austria, France, Germany, Greece, Italy, Japan, Malaysia, Netherlands, North Macedonia, Romania, South Africa, Spain, Taiwan, Thailand, Turkey (Türkiye), United Kingdom, United States
Participant flow
Recruitment details
The study was conducted at 10 sites in 8 countries : Italy (1 site), Malaysia (1 site), Romania (1 site), South Africa (1 site), Taiwan (1 site), Turkey (1 SIte), UK (2 sites), US (2 sites).
Pre-assignment details
Patients enrolled in the present trial were recruited from the pivotal trial (NN7999-3747) or the extension trial (NN7999-3775). In addition, new patients were recruited into the present trial.
Participants by arm
| Arm | Count |
|---|---|
| Nonacog Beta Pegol New patients as well as transferred patients from the pivotal trial (NN7999-3747) or the extension trial(NN7999-3775) received nonacog beta pegol at screening and followed a preventive treatment regimen with nonacog beta pegol until one week before the day of surgery. No more than 4 hours prior to the planned surgical procedure, all patients received a single bolus injection of 80 U/kg of nonacog beta pegol. Postoperatively, the patients received fixed doses of 40 U/kg repeated at the investigator's discretion aiming for no less than the FIX levels recommended by the World Federation of Hemophilia. Nonacog beta pegol was administered intravenously. The new patients were dosed once with 40 U/kg nonacog beta pegol at screening.From the day after surgery (Day 1) and through Day 6, nonacog beta pegol dosing was adjusted to aim for a FIX activity level of approximately 0.50 U/mL. | 13 |
| Total | 13 |
Baseline characteristics
| Characteristic | Nonacog Beta Pegol |
|---|---|
| Age, Categorical <=18 years | 1 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 12 Participants |
| Age, Continuous | 39 years FULL_RANGE 12.6 |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 13 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 9 / 13 |
| serious Total, serious adverse events | 0 / 13 |
Outcome results
Primary
Haemostatic Effect During Surgery Evaluated by the Four-point Response Scale (Excellent, Good, Moderate, Poor)
Haemostatic effect during surgery was evaluated immediately after surgery (last stitch) using a fourpoint response scale: \- Four-point response scale: Excellent, good, moderate, poor. The evaluation was done by the surgeon, anaesthesiologist and/or investigator based on experience as follows: 1. Excellent: Better than expected/predicted in this type of procedure. 2. Good: As expected in this type of procedure. 3. Moderate: Less than optimal for the type of procedure but haemostatic response maintained without change of treatment regimen. 4. Poor: Bleeding due to inadequate therapeutic response with adequate dosing, change of regimen required.
Time frame: At the day of surgery
Population: The full analysis set consisted of all patients exposed to nanacog beta pegol.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Nonacog Beta Pegol | Haemostatic Effect During Surgery Evaluated by the Four-point Response Scale (Excellent, Good, Moderate, Poor) | Excellent | 10 Haemostatic responses |
| Nonacog Beta Pegol | Haemostatic Effect During Surgery Evaluated by the Four-point Response Scale (Excellent, Good, Moderate, Poor) | Good | 3 Haemostatic responses |
| Nonacog Beta Pegol | Haemostatic Effect During Surgery Evaluated by the Four-point Response Scale (Excellent, Good, Moderate, Poor) | Moderate | 0 Haemostatic responses |
| Nonacog Beta Pegol | Haemostatic Effect During Surgery Evaluated by the Four-point Response Scale (Excellent, Good, Moderate, Poor) | Poor | 0 Haemostatic responses |
Secondary
Consumption of NNC-0156-0000-0009 (U/kg Body Weight)
Mean consumption of nonacog beta pegol (U/kg) used for treatment per patient before surgery, during surgery (the time from knife to skin until last stitch) and post-operative period.
Time frame: During surgery (the time from knife to skin until last stitch) and post-operative period (day 1 to day 13)
Population: The full analysis set consisted of all patients exposed to nanacog beta pegol.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Nonacog Beta Pegol | Consumption of NNC-0156-0000-0009 (U/kg Body Weight) | 328.2 U/Kg | Standard Deviation 113.1 |
Secondary
Haemoglobin Pre- and Post-surgery Start
The mean pre-surgery and post surgery haemoglobin level.
Time frame: 0, 1 hour, 24 hours.
Population: The full analysis set consisted of all patients exposed to nanacog beta pegol.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Nonacog Beta Pegol | Haemoglobin Pre- and Post-surgery Start | prior to surgery | 8.98 mmol/L | Standard Deviation 0.67 |
| Nonacog Beta Pegol | Haemoglobin Pre- and Post-surgery Start | 1 hour post-surgery | 8.37 mmol/L | Standard Deviation 0.78 |
| Nonacog Beta Pegol | Haemoglobin Pre- and Post-surgery Start | 24 hours post surgery | 7.99 mmol/L | Standard Deviation 1.13 |
Secondary
Incidence of Adverse Events (AEs)
The number of adverse events per patient years of exposure, reported during the trial period. Number is the only available option here, the data presented are rate of AEs.
Time frame: during the trial period (2-8 weeks prior to day of surgery (transferred subjects) or 2-4 weeks prior to day of surgery (new subjects) until 4 weeks after post-operative period (day 1 to day 13)
Population: The safety analysis set consisted of all patients exposed to nanacog beta pegol.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Nonacog Beta Pegol | Incidence of Adverse Events (AEs) | 12.12 events per patient year of exposure |
Secondary
Incidence of Inhibitors Against FIX (Coagulation Factor Nine)
Number of patients with inhibitory antibodies
Time frame: During the trial period (2-8 weeks prior to day of surgery (transferred subjects) or 2-4 weeks prior to day of surgery (new subjects) and every 4 weeks after post-operative period (day 1 to day 13)
Population: The full analysis set consisted of all patients exposed to nanacog beta pegol.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Nonacog Beta Pegol | Incidence of Inhibitors Against FIX (Coagulation Factor Nine) | 0 patients |
Secondary
Incidence of Serious Adverse Events (SAE)
The number of serious adverse events per patient years of exposure, reported during the trial period. Number is the only available option here, the data presented are rate of AEs.
Time frame: During the trial period (2-8 weeks prior to day of surgery (transferred subjects) or 2-4 weeks prior to day of surgery (new subjects) until 4 weeks after post-operative period (day 1 to day 13)
Population: The safety analysis set consisted of all patients exposed to nanacog beta pegol.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Nonacog Beta Pegol | Incidence of Serious Adverse Events (SAE) | 0 Events per patient year of exposure |
Secondary
Transfusion Requirements (Fulfilling Transfusion Criteria)
Mean quantity of transfusion during surgery (the time from knife to skin until last stitch) and the postoperative period (Day 1-13).None of the patients required transfusions beyond Day 6 hence no values presented for days 7-13.
Time frame: during surgery (the time from knife to skin until last stitch) and post-operative period (day 1 to day 13)
Population: The full analysis set consisted of all patients exposed to nanacog beta pegol.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Nonacog Beta Pegol | Transfusion Requirements (Fulfilling Transfusion Criteria) | During surgery | 275 mL | Standard Deviation 35.4 |
| Nonacog Beta Pegol | Transfusion Requirements (Fulfilling Transfusion Criteria) | Post surgery through day 6 | 266.7 mL | Standard Deviation 28.9 |